Research

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18 pages, 6830 KiB

Open AccessArticle

Novel Kefir Exopolysaccharides (KEPS) Mitigate Lipopolysaccharide (LPS)-Induced Systemic Inflammation in Luciferase Transgenic Mice through Inhibition of the NF-κB Pathway

by Chun-Huei Liao, Chih-Ching Yen, Hsiao-Ling Chen, Yu-Hsien Liu, Yu-Hsuan Chen, Ying-Wei Lan, Ke-Rong Chen, Wei Chen and Chuan-Mu Chen

Antioxidants 2023, 12(9), 1724; https://doi.org/10.3390/antiox12091724 - 05 Sep 2023

Cited by 2 | Viewed by 996

Abstract

A novel kefir exopolysaccharides (KEPS) derived from kefir grain fermentation were found to have a small molecular weight (12 kDa) compared to the traditionally high molecular weight (12,000 kDa) of kefiran (KE). KE has been shown to possess antioxidant, blood pressure-lowering, and immune-modulating [...] Read more.

A novel kefir exopolysaccharides (KEPS) derived from kefir grain fermentation were found to have a small molecular weight (12 kDa) compared to the traditionally high molecular weight (12,000 kDa) of kefiran (KE). KE has been shown to possess antioxidant, blood pressure-lowering, and immune-modulating effects. In this study, we characterized KEPS and KE and evaluated their anti-inflammatory properties in vitro using RAW264.7 macrophages. The main monosaccharide components were identified as glucose (98.1 ± 0.06%) in KEPS and galactose (45.36 ± 0.16%) and glucose (47.13 ± 0.06%) in KE, respectively. Both KEPS and KE significantly reduced IL-6 secretion in lipopolysaccharide (LPS)-stimulated macrophages. We further investigated their effects in LPS-induced systemic injury in male and female NF-κB-luciferase^+/+ transgenic mice. Mice received oral KEPS (100 mg/kg) or KE (100 mg/kg) for seven days, followed by LPS or saline injection. KEPS and KE inhibited NF-κB signaling, as indicated by reduced luciferase expression and phosphorylated NF-κB levels. LPS-induced systemic injury increased luciferase signals, especially in the kidney, spleen, pancreas, lung, and gut tissues of female mice compared to male mice. Additionally, it upregulated inflammatory mediators in these organs. However, KEPS and KE effectively suppressed the expression of inflammatory mediators, including p-MAPK and IL-6. These findings demonstrate that KEPS can alleviate LPS-induced systemic damage by inhibiting NF-κB/MAPK signaling, suggesting their potential as a treatment for inflammatory disorders. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation as Targets for Novel Preventive and Therapeutic Approaches in Non-Communicable Diseases III)

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16 pages, 10320 KiB

Open AccessArticle

Caffeic Acid, a Polyphenolic Micronutrient Rescues Mice Brains against Aβ-Induced Neurodegeneration and Memory Impairment

by Amjad Khan, Jun Sung Park, Min Hwa Kang, Hyeon Jin Lee, Jawad Ali, Muhammad Tahir, Kyonghwan Choe and Myeong Ok Kim

Antioxidants 2023, 12(6), 1284; https://doi.org/10.3390/antiox12061284 - 15 Jun 2023

Cited by 3 | Viewed by 1662

Abstract

Oxidative stress plays an important role in cognitive dysfunctions and is seen in neurodegeneration and Alzheimer’s disease (AD). It has been reported that the polyphenolic compound caffeic acid possesses strong neuroprotective and antioxidant effects. The current study was conducted to investigate the therapeutic [...] Read more.

Oxidative stress plays an important role in cognitive dysfunctions and is seen in neurodegeneration and Alzheimer’s disease (AD). It has been reported that the polyphenolic compound caffeic acid possesses strong neuroprotective and antioxidant effects. The current study was conducted to investigate the therapeutic potential of caffeic acid against amyloid beta (Aβ_1–42)-induced oxidative stress and memory impairments. Aβ_1–42 (5 μL/5 min/mouse) was administered intracerebroventricularly (ICV) into wild-type adult mice to induce AD-like pathological changes. Caffeic acid was administered orally at 50 mg/kg/day for two weeks to AD mice. Y-maze and Morris water maze (MWM) behavior tests were conducted to assess memory and cognitive abilities. Western blot and immunofluorescence analyses were used for the biochemical analyses. The behavioral results indicated that caffeic acid administration improved spatial learning, memory, and cognitive abilities in AD mice. Reactive oxygen species (ROS) and lipid peroxidation (LPO) assays were performed and showed that the levels of ROS and LPO were markedly reduced in the caffeic acid-treated mice, as compared to Aβ-induced AD mice brains. Moreover, the expression of nuclear factor erythroid 2–related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were regulated with the administration of caffeic acid, compared to the Aβ-injected mice. Next, we checked the expression of ionized calcium-binding adaptor molecule 1 (Iba-1), glial fibrillary acidic proteins (GFAP), and other inflammatory markers in the experimental mice, which suggested enhanced expression of these markers in AD mice brains, and were reduced with caffeic acid treatment. Furthermore, caffeic acid enhanced synaptic markers in the AD mice model. Additionally, caffeic acid treatment also decreased Aβ and BACE-1 expression in the Aβ-induced AD mice model. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation as Targets for Novel Preventive and Therapeutic Approaches in Non-Communicable Diseases III)

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21 pages, 2850 KiB

Open AccessArticle

Synergistic Combination of Citrus Flavanones as Strong Antioxidant and COX-Inhibitor Agent

by Antonella Smeriglio, Nunzio Iraci, Marcella Denaro, Giuseppina Mandalari, Salvatore Vincenzo Giofrè and Domenico Trombetta

Antioxidants 2023, 12(4), 972; https://doi.org/10.3390/antiox12040972 - 21 Apr 2023

Cited by 2 | Viewed by 1523

Abstract

Recently, we demonstrated that a Citrus flavanone mix (FM) shows antioxidant and anti-inflammatory activity, even after gastro-duodenal digestion (DFM). The aim of this study was to investigate the possible involvement of the cyclooxygenases (COXs) in the anti-inflammatory activity previously detected, using a human [...] Read more.

Recently, we demonstrated that a Citrus flavanone mix (FM) shows antioxidant and anti-inflammatory activity, even after gastro-duodenal digestion (DFM). The aim of this study was to investigate the possible involvement of the cyclooxygenases (COXs) in the anti-inflammatory activity previously detected, using a human COX inhibitor screening assay, molecular modeling studies, and PGE2 release by Caco-2 cells stimulated with IL-1β and arachidonic acid. Furthermore, the ability to counteract pro-oxidative processes induced by IL-1β was evaluated by measuring four oxidative stress markers, namely, carbonylated proteins, thiobarbituric acid-reactive substances, reactive oxygen species, and reduced glutathione/oxidized glutathione ratio in Caco-2 cells. All flavonoids showed a strong inhibitory activity on COXs, confirmed by molecular modeling studies, with DFM, which showed the best and most synergistic activity on COX-2 (82.45% vs. 87.93% of nimesulide). These results were also corroborated by the cell-based assays. Indeed, DFM proves to be the most powerful anti-inflammatory and antioxidant agent reducing, synergistically and in a statistically significant manner (p < 0.05), PGE2 release than the oxidative stress markers, also with respect to the nimesulide and trolox used as reference compounds. This leads to the hypothesis that FM could be an excellent antioxidant and COX inhibitor candidate to counteract intestinal inflammation. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation as Targets for Novel Preventive and Therapeutic Approaches in Non-Communicable Diseases III)

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21 pages, 5073 KiB

Open AccessArticle

Pharmacological Inhibition of Lysine-Specific Demethylase 1A Reduces Atherosclerotic Lesion Formation in Apolipoprotein E-Deficient Mice by a Mechanism Involving Decreased Oxidative Stress and Inflammation; Potential Implications in Human Atherosclerosis

by Simona-Adriana Manea, Mihaela-Loredana Vlad, Alexandra-Gela Lazar, Horia Muresian, Maya Simionescu and Adrian Manea

Antioxidants 2022, 11(12), 2382; https://doi.org/10.3390/antiox11122382 - 01 Dec 2022

Viewed by 1826

Abstract

Dysregulated epigenetic mechanisms promote transcriptomic and phenotypic alterations in cardiovascular diseases. The role of histone methylation-related pathways in atherosclerosis is largely unknown. We hypothesize that lysine-specific demethylase 1A (LSD1/KDM1A) regulates key molecular effectors and pathways linked to atherosclerotic plaque formation. Human non-atherosclerotic and [...] Read more.

Dysregulated epigenetic mechanisms promote transcriptomic and phenotypic alterations in cardiovascular diseases. The role of histone methylation-related pathways in atherosclerosis is largely unknown. We hypothesize that lysine-specific demethylase 1A (LSD1/KDM1A) regulates key molecular effectors and pathways linked to atherosclerotic plaque formation. Human non-atherosclerotic and atherosclerotic tissue specimens, ApoE-/- mice, and in vitro polarized macrophages (Mac) were examined. Male ApoE-/- mice fed a normal/atherogenic diet were randomized to receive GSK2879552, a highly specific LSD1 inhibitor, or its vehicle, for 4 weeks. The mRNA and protein expression levels of LSD1/KDM1A were significantly elevated in atherosclerotic human carotid arteries, atherosclerotic aortas of ApoE-/- mice, and M1-Mac. Treatment of ApoE-/- mice with GSK2879552 significantly reduced the extent of atherosclerotic lesions and the aortic expression of NADPH oxidase subunits (Nox1/2/4, p22phox) and 4-hydroxynonenal-protein adducts. Concomitantly, the markers of immune cell infiltration and vascular inflammation were significantly decreased. LSD1 blockade down-regulated the expression of genes associated with Mac pro-inflammatory phenotype. Nox subunit transcript levels were significantly elevated in HEK293 reporter cells overexpressing LSD1. In experimental atherosclerosis, LSD1 mediates the up-regulation of molecular effectors connected to oxidative stress and inflammation. Together, these data indicate that LSD1-pharmacological interventions are novel targets for supportive therapeutic strategies in atherosclerosis. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation as Targets for Novel Preventive and Therapeutic Approaches in Non-Communicable Diseases III)

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13 pages, 12166 KiB

Open AccessArticle

Gastroprotective Effect of Anisomeles indica on Aspirin-Induced Gastric Ulcer in Mice

by Hsiu-Man Lien, Yu-Yen Wang, Mei-Zi Huang, Hui-Yu Wu, Chao-Lu Huang, Chia-Chi Chen, Shao-Wen Hung, Chia-Chang Chen, Cheng-Hsun Chiu and Chih-Ho Lai

Antioxidants 2022, 11(12), 2327; https://doi.org/10.3390/antiox11122327 - 24 Nov 2022

Cited by 2 | Viewed by 2045

Abstract

Gastric ulcers are commonly seen in the upper gastrointestinal tract and may be related to the Helicobacter pylori infection and the use of aspirin, a nonsteroidal anti-inflammatory drug (NSAID). Typically, proton-pump inhibitors (PPIs) are used to treat gastric ulcers; however, adverse effects have [...] Read more.

Gastric ulcers are commonly seen in the upper gastrointestinal tract and may be related to the Helicobacter pylori infection and the use of aspirin, a nonsteroidal anti-inflammatory drug (NSAID). Typically, proton-pump inhibitors (PPIs) are used to treat gastric ulcers; however, adverse effects have emerged following long-term treatment. Natural medicines are used as alternative therapeutic agents in the treatment of gastric ulcers, with few side effects. Despite various reports on the anti-H. pylori and anti-gastric cancer activities of Anisomeles indica, its gastroprotective effect on ulcers remains undetermined. This study investigated the protective effect of A. indica on aspirin-induced gastric ulcers in murine models. Our results show that three fractions of ethanol-extracted A. indica inhibited aspirin-induced gastric injury. Among these, A. indica Fraction 1 was observed to enrich ovatodiolide, which effectively diminished gastric acidity and alleviated aspirin-induced inflammation in the stomach. Our results provide evidence that A. indica could be developed as an effective therapeutic agent for gastroprotective purposes. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation as Targets for Novel Preventive and Therapeutic Approaches in Non-Communicable Diseases III)

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22 pages, 4322 KiB

Open AccessArticle

An Oleocanthal-Enriched EVO Oil Extract Induces the ROS Production in Gastric Cancer Cells and Potentiates the Effect of Chemotherapy

by Sara Peri, Jessica Ruzzolini, Silvia Urciuoli, Giampaolo Versienti, Alessio Biagioni, Elena Andreucci, Silvia Peppicelli, Francesca Bianchini, Andrea Bottari, Lido Calorini, Chiara Nediani, Lucia Magnelli and Laura Papucci

Antioxidants 2022, 11(9), 1762; https://doi.org/10.3390/antiox11091762 - 07 Sep 2022

Cited by 7 | Viewed by 1688

Abstract

Oleocanthal, a minor polar compound in extra-virgin olive (EVO) oil, contains anticancer properties, which should be encouraged in its use in oncology. Gastric Cancer (GC), a very aggressive human cancer, is often diagnosed at advanced stages, when surgery is substituted or supported by [...] Read more.

Oleocanthal, a minor polar compound in extra-virgin olive (EVO) oil, contains anticancer properties, which should be encouraged in its use in oncology. Gastric Cancer (GC), a very aggressive human cancer, is often diagnosed at advanced stages, when surgery is substituted or supported by chemotherapy (CT). However, CT frequently fails due to the patient’s resistance to the treatment. Thus, the aim of this study is to verify whether an OC-enriched EVO oil extract fraction (OCF) may be useful in order to overcome a resistance to GC. We evaluated the OCF effects on an AGS gastric adenocarcinoma cell line wild type (AGS wt) and on its subpopulations resistant to 5-fluorouracil (5FUr), Paclitaxel (TAXr) or cisplatin (CISr). We found that a 60 µM dose of the OCF acts on the AGS wt, 5FUr and TAXr, leading to the cell cycle inhibition and to a ROS production, but not on CISr cells. Resistance of CISr to the OCF seems to be due to higher levels of antioxidant-enzymes that can counteract the OCF-induced ROS production. Moreover, using the OCF plus 5-fluorouracil, Paclitaxel or cisplatin, we found a potentiating effect compared with a mono-treatment in all resistant GC cells, including CISr. In conclusion, the use of the OCF in the management of GC has shown very interesting advantages, opening-up the possibility to evaluate the efficacy of the OCF in vivo, as a valid adjuvant in the treatment of resistant GC. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation as Targets for Novel Preventive and Therapeutic Approaches in Non-Communicable Diseases III)

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23 pages, 3904 KiB

Open AccessArticle

Intrarenal Arterial Transplantation of Dexmedetomidine Preconditioning Adipose Stem-Cell-Derived Microvesicles Confers Further Therapeutic Potential to Attenuate Renal Ischemia/Reperfusion Injury through miR-122-5p/Erythropoietin/Apoptosis Axis

by Yu-Hsuan Cheng, Kuo-Hsin Chen, Yi-Ting Sung, Chih-Ching Yang and Chiang-Ting Chien

Antioxidants 2022, 11(9), 1702; https://doi.org/10.3390/antiox11091702 - 30 Aug 2022

Cited by 3 | Viewed by 1647

Abstract

Intravenous adipose mesenchymal stem cells (ADSCs) attenuate renal ischemia/reperfusion (IR) injury but with major drawbacks, including the lack of a specific homing effect after systemic infusion, cell trapping in the lung, and early cell death in the damaged microenvironment. We examined whether intrarenal [...] Read more.

Intravenous adipose mesenchymal stem cells (ADSCs) attenuate renal ischemia/reperfusion (IR) injury but with major drawbacks, including the lack of a specific homing effect after systemic infusion, cell trapping in the lung, and early cell death in the damaged microenvironment. We examined whether intrarenal arterial transplantation of dexmedetomidine (DEX) preconditioning ADSC-derived microvesicles (DEX-MVs) could promote further therapeutic potential to reduce renal IR injury. We evaluated the effect of DEX-MVs on NRK-52E cells migration, hypoxia/reoxygenation (H/R)-induced cell death, and reactive oxygen species (ROS) amount and renal IR model in rats. IR was established by bilateral 45 min ischemia followed by 4 h reperfusion. Intrarenal MVs or DEX-MVs were administered prior to ischemia. Renal oxidative stress, hemodynamics and function, western blot, immunohistochemistry, and tubular injury scores were determined. The miR-122-5p expression in kidneys was analyzed using microarrays and quantitative RT-PCR and its action target was predicted by TargetScan. DEX-MVs were more efficient than MVs to increase migration capability and to further decrease H/R-induced cell death and ROS level in NRK-52E cells. Consistently, DEX-MVs were better than MV in increasing CD44 expression, improving IR-depressed renal hemodynamics and renal erythropoietin expression, inhibiting IR-enhanced renal ROS level, tubular injury score, miR-122-5p expression, pNF-κB expression, Bax/caspase 3/poly(ADP-ribose) polymerase (PARP)-mediated apoptosis, blood urea nitrogen, and creatinine levels. The use of NRK-52E cells confirmed that miR-122-5p mimic via inhibiting erythropoietin expression exacerbated Bax-mediated apoptosis, whereas miR-122-5p inhibitor via upregulating erythropoietin and Bcl-2 expression reduced apoptosis. In summary, intrarenal arterial DEX-MV conferred further therapeutic potential to reduce renal IR injury through the miR-122-5p/erythropoietin/apoptosis axis. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation as Targets for Novel Preventive and Therapeutic Approaches in Non-Communicable Diseases III)

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16 pages, 2462 KiB

Open AccessArticle

Effects of 2-Year Nutritional and Lifestyle Intervention on Oxidative and Inflammatory Statuses in Individuals of 55 Years of Age and over at High Cardiovascular Risk

by Margalida Monserrat-Mesquida, Magdalena Quetglas-Llabrés, Cristina Bouzas, Silvia García, David Mateos, Cristina Gómez, José M. Gámez, Henrik E. Poulsen, Josep A. Tur and Antoni Sureda

Antioxidants 2022, 11(7), 1326; https://doi.org/10.3390/antiox11071326 - 05 Jul 2022

Cited by 5 | Viewed by 2135

Abstract

Obesity and overweight are disorders with high impact on the morbidity and mortality of chronic diseases, such as type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD). We aim to assess the effects of 2-year nutritional and lifestyle intervention on oxidative and inflammatory [...] Read more.

Obesity and overweight are disorders with high impact on the morbidity and mortality of chronic diseases, such as type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD). We aim to assess the effects of 2-year nutritional and lifestyle intervention on oxidative and inflammatory status in individuals of 55 years of age and over at high CVD risk. Participants (n = 100 individuals of 55 years of age and over living in the Balearic Islands, Spain) were randomized into control and intervention group. Anthropometric and haematological parameters, blood pressure and physical activity were measured before and after the intervention. Oxidative and inflammatory biomarkers in plasma, urine, peripheral blood mononuclear cells (PBMCs) and neutrophils were determined. A higher reduction in abdominal obesity, blood pressure and triglycerides levels was observed after a 2-year intervention. An improvement of oxidative stress and proinflammatory status was demonstrated with a significant reduction in myeloperoxidase, xanthine oxidase, malondialdehyde and monocyte chemoattractant protein-1 (MCP1) levels, and an increase in polyphenols in plasma was observed. A decrease in reactive oxygen species production in PBMCs and neutrophils levels after zymosan and lipopolysaccharide activation was found in the intervention group with respect to the control group. The intervention with hypocaloric Mediterranean Diet and customized physical activity improves oxidative stress and proinflammatory status and could contribute to decreasing the CVD risk. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation as Targets for Novel Preventive and Therapeutic Approaches in Non-Communicable Diseases III)

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18 pages, 3735 KiB

Open AccessArticle

SOD3 and IL-18 Predict the First Kidney Disease-Related Hospitalization or Death during the One-Year Follow-Up Period in Patients with End-Stage Renal Disease

by Yu-Hsien Liu, Yu-Hsuan Chen, Chi-Hua Ko, Chia-Wen Kuo, Chih-Ching Yen, Wei Chen, Kowit-Yu Chong and Chuan-Mu Chen

Antioxidants 2022, 11(6), 1198; https://doi.org/10.3390/antiox11061198 - 18 Jun 2022

Cited by 2 | Viewed by 1904

Abstract

End-stage renal disease (ESRD) patients experience oxidative stress due to excess exogenous or endogenous oxidants and insufficient antioxidants. Hence, oxidative stress and inflammation cause endothelial damage, contributing to vascular dysfunction and atherosclerosis. Therefore, ESRD patients suffer more cardiovascular and hospitalization events than healthy [...] Read more.

End-stage renal disease (ESRD) patients experience oxidative stress due to excess exogenous or endogenous oxidants and insufficient antioxidants. Hence, oxidative stress and inflammation cause endothelial damage, contributing to vascular dysfunction and atherosclerosis. Therefore, ESRD patients suffer more cardiovascular and hospitalization events than healthy people. This study aims to test the correlations between ROS, SOD3, IL-2, IL-6, and IL-18 and the first kidney disease-related hospitalization or death events in ESRD patients undergoing regular hemodialysis. A total of 212 participants was enrolled, including 45 normal healthy adults and 167 ESRD patients on regular dialysis. Blood samples from all participants were collected for ROS, SOD3, IL-2, IL-6, and IL-18 measurement at the beginning of the study, and every kidney disease-related admission or death was recorded for the next year. Multivariate analysis was conducted by fitting a linear regression model, logistic regression model, and Cox proportional hazards model to estimate the adjusted effects of risk factors, prognostic factors, or predictors on continuous, binary, and survival outcome data. The results showed that plasma SOD3 and serum IL-18 were two strong predictors of the first kidney disease-related hospitalization or death. In the Cox proportional hazards models (run in R), higher IL-18 concentration (>69.054 pg/mL) was associated with a hazard ratio of 3.376 for the first kidney disease-related hospitalization or death (95% CI: 1.2644 to 9.012), while log(SOD3) < 4.723 and dialysis clearance (Kt/V; 1.11 < value < 1.869) had a hazard ratio = 0.2730 (95% CI: 0.1133 to 0.6576) for reducing future kidney disease-related hospitalization or death. Other markers, including body mass index (BMI), transferrin saturation, total iron binding capacity, and sodium and alkaline phosphate, were also found to be significant in our study. These results reveal the new predictors SOD3 and IL-18 for the medical care of end-stage renal disease patients. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation as Targets for Novel Preventive and Therapeutic Approaches in Non-Communicable Diseases III)

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15 pages, 4975 KiB

Open AccessArticle

Paraoxonase-1 Regulation of Renal Inflammation and Fibrosis in Chronic Kidney Disease

by Fatimah K. Khalaf, Chrysan J. Mohammed, Prabhatchandra Dube, Jacob A. Connolly, Apurva Lad, Usman M. Ashraf, Joshua D. Breidenbach, Robin C. Su, Andrew L. Kleinhenz, Deepak Malhotra, Amira F. Gohara, Steven T. Haller and David J. Kennedy

Antioxidants 2022, 11(5), 900; https://doi.org/10.3390/antiox11050900 - 30 Apr 2022

Cited by 7 | Viewed by 1988

Abstract

Papraoxonase-1 (PON1) is a hydrolytic lactonase enzyme that is synthesized in the liver and circulates attached to high-density lipoproteins (HDL). Clinical studies have demonstrated an association between diminished PON-1 and the progression of chronic kidney disease (CKD). However, whether decreased PON-1 is mechanistically [...] Read more.

Papraoxonase-1 (PON1) is a hydrolytic lactonase enzyme that is synthesized in the liver and circulates attached to high-density lipoproteins (HDL). Clinical studies have demonstrated an association between diminished PON-1 and the progression of chronic kidney disease (CKD). However, whether decreased PON-1 is mechanistically linked to renal injury is unknown. We tested the hypothesis that the absence of PON-1 is mechanistically linked to the progression of renal inflammation and injury in CKD. Experiments were performed on control Dahl salt-sensitive rats (SS^Mcwi, hereafter designated SS rats) and Pon1 knock-out rats (designated SS-Pon1^em1Mcwi, hereafter designated SS-PON-1 KO rats) generated by injecting a CRISPR targeting the sequence into SS^Mcwi rat embryos. The resulting mutation is a 7 bp frameshift insertion in exon 4 of the PON-1 gene. First, to examine the renal protective role of PON-1 in settings of CKD, ten-week-old, age-matched male rats were maintained on a high-salt diet (8% NaCl) for up to 5 weeks to initiate the salt-sensitive hypertensive renal disease characteristic of this model. We found that SS-PON-1 KO rats demonstrated several hallmarks of increased renal injury vs. SS rats including increased renal fibrosis, sclerosis, and tubular injury. SS-PON-1 KO also demonstrated increased recruitment of immune cells in the renal interstitium, as well as increased expression of inflammatory genes compared to SS rats (all p < 0.05). SS-PON-1 KO rats also showed a significant (p < 0.05) decline in renal function and increased renal oxidative stress compared to SS rats, despite no differences in blood pressure between the two groups. These findings suggest a new role for PON-1 in regulating renal inflammation and fibrosis in the setting of chronic renal disease independent of blood pressure. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation as Targets for Novel Preventive and Therapeutic Approaches in Non-Communicable Diseases III)

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Review

Jump to: Research

28 pages, 1973 KiB

Open AccessReview

Anthocyanin Effects on Vascular and Endothelial Health: Evidence from Clinical Trials and Role of Gut Microbiota Metabolites

by Samuele Laudani, Justyna Godos, Federica Martina Di Domenico, Ignazio Barbagallo, Cinzia Lucia Randazzo, Gian Marco Leggio, Fabio Galvano and Giuseppe Grosso

Antioxidants 2023, 12(9), 1773; https://doi.org/10.3390/antiox12091773 - 18 Sep 2023

Cited by 4 | Viewed by 1235

Abstract

Hypertension and derived cardiovascular disease (CVD) are among the leading causes of death worldwide. Increased oxidative stress and inflammatory state are involved in different alterations in endothelial functions that contribute to the onset of CVD. Polyphenols, and in particular anthocyanins, have aroused great [...] Read more.

Hypertension and derived cardiovascular disease (CVD) are among the leading causes of death worldwide. Increased oxidative stress and inflammatory state are involved in different alterations in endothelial functions that contribute to the onset of CVD. Polyphenols, and in particular anthocyanins, have aroused great interest for their antioxidant effects and their cardioprotective role. However, anthocyanins are rarely detected in blood serum because they are primarily metabolized by the gut microbiota. This review presents studies published to date that report the main results from clinical studies on the cardioprotective effects of anthocyanins and the role of the gut microbiota in the metabolism and bioavailability of anthocyanins and their influence on the composition of the microbiota. Even if it seems that anthocyanins have a significant effect on vascular health, more studies are required to better clarify which molecules and doses show vascular benefits without forgetting the crucial role of the microbiota. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation as Targets for Novel Preventive and Therapeutic Approaches in Non-Communicable Diseases III)

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21 pages, 753 KiB

Open AccessReview

Physical Activity as a Modern Intervention in the Fight against Obesity-Related Inflammation in Type 2 Diabetes Mellitus and Gestational Diabetes

by Katarzyna Piotrowska, Katarzyna Zgutka, Marta Tkacz and Maciej Tarnowski

Antioxidants 2023, 12(8), 1488; https://doi.org/10.3390/antiox12081488 - 25 Jul 2023

Cited by 1 | Viewed by 1518

Abstract

Diabetes is one of the greatest healthcare problems; it requires an appropriate approach to the patient, especially when it concerns pregnant women. Gestational diabetes mellitus (GDM) is a common metabolic condition in pregnancy that shares many features with type 2 diabetes mellitus (T2DM). [...] Read more.

Diabetes is one of the greatest healthcare problems; it requires an appropriate approach to the patient, especially when it concerns pregnant women. Gestational diabetes mellitus (GDM) is a common metabolic condition in pregnancy that shares many features with type 2 diabetes mellitus (T2DM). T2DM and GDM induce oxidative stress, which activates cellular stress signalling. In addition, the risk of diabetes during pregnancy can lead to various complications for the mother and foetus. It has been shown that physical activity is an important tool to not only treat the negative effects of diabetes but also to prevent its progression or even reverse the changes already made by limiting the inflammatory process. Physical activity has a huge impact on the immune status of an individual. Various studies have shown that regular training sessions cause changes in circulating immune cell levels, cytokine activation, production and secretion and changes in microRNA, all of which have a positive effect on the well-being of the diabetic patient, mother and foetus. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation as Targets for Novel Preventive and Therapeutic Approaches in Non-Communicable Diseases III)

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27 pages, 1057 KiB

Open AccessReview

Comprehensive Approach to Medical Nutrition Therapy in Patients with Type 2 Diabetes Mellitus: From Diet to Bioactive Compounds

by Luigi Barrea, Claudia Vetrani, Ludovica Verde, Evelyn Frias-Toral, Florencia Ceriani, Simona Cernea, Annamaria Docimo, Chiara Graziadio, Devjit Tripathy, Silvia Savastano, Annamaria Colao and Giovanna Muscogiuri

Antioxidants 2023, 12(4), 904; https://doi.org/10.3390/antiox12040904 - 10 Apr 2023

Cited by 4 | Viewed by 6235

Abstract

In the pathogenesis of type 2 diabetes mellitus (T2DM), diet plays a key role. Individualized medical nutritional therapy, as part of lifestyle optimization, is one of the cornerstones for the management of T2DM and has been shown to improve metabolic outcomes. This paper [...] Read more.

In the pathogenesis of type 2 diabetes mellitus (T2DM), diet plays a key role. Individualized medical nutritional therapy, as part of lifestyle optimization, is one of the cornerstones for the management of T2DM and has been shown to improve metabolic outcomes. This paper discusses major aspects of the nutritional intervention (including macro- and micronutrients, nutraceuticals, and supplements), with key practical advice. Various eating patterns, such as the Mediterranean-style, low-carbohydrate, vegetarian or plant-based diets, as well as healthy eating plans with caloric deficits have been proven to have beneficial effects for patients with T2DM. So far, the evidence does not support a specific macronutrient distribution and meal plans should be individualized. Reducing the overall carbohydrate intake and replacing high glycemic index (GI) foods with low GI foods have been shown as valid options for patients with T2DM to improve glycemic control. Additionally, evidence supports the current recommendation to reduce the intake of free sugars to less than 10% of total energy intake, since their excessive intake promotes weight gain. The quality of fats seems to be rather important and the substitution of saturated and trans fatty acids with foods rich in monounsaturated and polyunsaturated fats lowers cardiovascular risk and improves glucose metabolism. There is no benefit of supplementation with antioxidants, such as carotene, vitamins E and C, or other micronutrients, due to the lack of consistent evidence showing efficacy and long-term safety. Some studies suggest possible beneficial metabolic effects of nutraceuticals in patients with T2DM, but more evidence about their efficacy and safety is still needed. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation as Targets for Novel Preventive and Therapeutic Approaches in Non-Communicable Diseases III)

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32 pages, 539 KiB

Open AccessReview

Revisiting the Role of Vitamins and Minerals in Alzheimer’s Disease

by Harsh Shah, Fereshteh Dehghani, Marjan Ramezan, Ritchel B. Gannaban, Zobayda Farzana Haque, Fatemeh Rahimi, Soheil Abbasi and Andrew C. Shin

Antioxidants 2023, 12(2), 415; https://doi.org/10.3390/antiox12020415 - 08 Feb 2023

Cited by 8 | Viewed by 6135

Abstract

Alzheimer’s disease (AD) is the most common type of dementia that affects millions of individuals worldwide. It is an irreversible neurodegenerative disorder that is characterized by memory loss, impaired learning and thinking, and difficulty in performing regular daily activities. Despite nearly two decades [...] Read more.

Alzheimer’s disease (AD) is the most common type of dementia that affects millions of individuals worldwide. It is an irreversible neurodegenerative disorder that is characterized by memory loss, impaired learning and thinking, and difficulty in performing regular daily activities. Despite nearly two decades of collective efforts to develop novel medications that can prevent or halt the disease progression, we remain faced with only a few options with limited effectiveness. There has been a recent growth of interest in the role of nutrition in brain health as we begin to gain a better understanding of what and how nutrients affect hormonal and neural actions that not only can lead to typical cardiovascular or metabolic diseases but also an array of neurological and psychiatric disorders. Vitamins and minerals, also known as micronutrients, are elements that are indispensable for functions including nutrient metabolism, immune surveillance, cell development, neurotransmission, and antioxidant and anti-inflammatory properties. In this review, we provide an overview on some of the most common vitamins and minerals and discuss what current studies have revealed on the link between these essential micronutrients and cognitive performance or AD. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation as Targets for Novel Preventive and Therapeutic Approaches in Non-Communicable Diseases III)

27 pages, 5101 KiB

Open AccessReview

Oxidative Stress and Natural Antioxidants in Osteoporosis: Novel Preventive and Therapeutic Approaches

by Gemma Marcucci, Vladana Domazetovic, Chiara Nediani, Jessica Ruzzolini, Claudio Favre and Maria Luisa Brandi

Antioxidants 2023, 12(2), 373; https://doi.org/10.3390/antiox12020373 - 03 Feb 2023

Cited by 25 | Viewed by 4306

Abstract

This review reports in detail the cellular and molecular mechanisms which regulate the bone remodeling process in relation to oxidative stress (OS), inflammatory factors, and estrogen deficiency. OS is considered an important pathogenic factor of osteoporosis, inducing osteocyte apoptosis and varying levels of [...] Read more.

This review reports in detail the cellular and molecular mechanisms which regulate the bone remodeling process in relation to oxidative stress (OS), inflammatory factors, and estrogen deficiency. OS is considered an important pathogenic factor of osteoporosis, inducing osteocyte apoptosis and varying levels of specific factors, such as receptor activator κB ligand (RANKL), sclerostin, and, according to recent evidence, fibroblast growth factor 23, with consequent impairment of bone remodeling and high bone resorption. Bone loss increases the risk of fragility fractures, and the most commonly used treatments are antiresorptive drugs, followed by anabolic drugs or those with a double effect. In addition, recent data show that natural antioxidants contained in the diet are efficient in preventing and reducing the negative effects of OS on bone remodeling and osteocytes through the involvement of sirtuin type 1 enzyme. Indeed, osteocytes and some of their molecular factors are considered potential biological targets on which antioxidants can act to prevent and reduce bone loss, as well as to promote bone anabolic and regenerative processes by restoring physiological bone remodeling. Several data suggest including antioxidants in novel therapeutic approaches to develop better management strategies for the prevention and treatment of osteoporosis and OS-related bone diseases. In particular, anthocyanins, as well as resveratrol, lycopene, oleuropein, some vitamins, and thiol antioxidants, could have protective and therapeutic anti-osteoporotic effects. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation as Targets for Novel Preventive and Therapeutic Approaches in Non-Communicable Diseases III)

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20 pages, 1234 KiB

Open AccessReview

Ageing and Low-Level Chronic Inflammation: The Role of the Biological Clock

by Barbara Colombini, Monica Dinu, Emanuele Murgo, Sofia Lotti, Roberto Tarquini, Francesco Sofi and Gianluigi Mazzoccoli

Antioxidants 2022, 11(11), 2228; https://doi.org/10.3390/antiox11112228 - 11 Nov 2022

Cited by 9 | Viewed by 3229

Abstract

Ageing is a multifactorial physiological manifestation that occurs inexorably and gradually in all forms of life. This process is linked to the decay of homeostasis due to the progressive decrease in the reparative and regenerative capacity of tissues and organs, with reduced physiological [...] Read more.

Ageing is a multifactorial physiological manifestation that occurs inexorably and gradually in all forms of life. This process is linked to the decay of homeostasis due to the progressive decrease in the reparative and regenerative capacity of tissues and organs, with reduced physiological reserve in response to stress. Ageing is closely related to oxidative damage and involves immunosenescence and tissue impairment or metabolic imbalances that trigger inflammation and inflammasome formation. One of the main ageing-related alterations is the dysregulation of the immune response, which results in chronic low-level, systemic inflammation, termed “inflammaging”. Genetic and epigenetic changes, as well as environmental factors, promote and/or modulate the mechanisms of ageing at the molecular, cellular, organ, and system levels. Most of these mechanisms are characterized by time-dependent patterns of variation driven by the biological clock. In this review, we describe the involvement of ageing-related processes with inflammation in relation to the functioning of the biological clock and the mechanisms operating this intricate interaction. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation as Targets for Novel Preventive and Therapeutic Approaches in Non-Communicable Diseases III)

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15 pages, 865 KiB

Open AccessReview

Roles of Oxidative Stress and Inflammation in Vascular Endothelial Dysfunction-Related Disease

by Yukihito Higashi

Antioxidants 2022, 11(10), 1958; https://doi.org/10.3390/antiox11101958 - 30 Sep 2022

Cited by 35 | Viewed by 6088

Abstract

Oxidative stress and chronic inflammation play an important role in the pathogenesis of atherosclerosis. Atherosclerosis develops as the first step of vascular endothelial dysfunction induced by complex molecular mechanisms. Vascular endothelial dysfunction leads to oxidative stress and inflammation of vessel walls, which in [...] Read more.

Oxidative stress and chronic inflammation play an important role in the pathogenesis of atherosclerosis. Atherosclerosis develops as the first step of vascular endothelial dysfunction induced by complex molecular mechanisms. Vascular endothelial dysfunction leads to oxidative stress and inflammation of vessel walls, which in turn enhances vascular endothelial dysfunction. Vascular endothelial dysfunction and vascular wall oxidative stress and chronic inflammation make a vicious cycle that leads to the development of atherosclerosis. Simultaneously capturing and accurately evaluating the association of vascular endothelial function with oxidative stress and inflammation would be useful for elucidating the pathophysiology of atherosclerosis, determining treatment efficacy, and predicting future cardiovascular complications. Intervention in both areas is expected to inhibit the progression of atherosclerosis and prevent cardiovascular complications. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation as Targets for Novel Preventive and Therapeutic Approaches in Non-Communicable Diseases III)

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