Feature Papers in Drug Toxicity

A special issue of Toxics (ISSN 2305-6304). This special issue belongs to the section "Drugs Toxicity".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 19153

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Guest Editor
Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, 3000 Arlington Ave., HEB282G, Toledo, OH 43614-2598, USA
Interests: alcohol dependence; methamphetamine; cocaine; nicotine; opioids; electronic cigarettes; drug dependence; glutamate transporters

Special Issue Information

Dear Colleagues,

Drug toxicity is a major problem involving neurotoxicity and organ injury. There are many drugs that have toxic effects as a result of acute or chronic exposure. Among these drugs are drugs of abuse, such as alcohol, methamphetamine, opioids, cocaine, cathinone, electronic cigarette, and cannabis-related chemicals. Understanding the pharmacological and toxicological nature of these drugs of abuse would expand research in the field of neurotoxicity and organ toxicity. It is unclear whether there are differences in acute vs. chronic exposure in terms of drug-induced toxicity and gender.

As part of this Special Issue, we are very pleased to invite investigators and scientists from different research areas to present papers related to drugs of abuse in animal models and clinics. This will involve publications of original research, review articles and research method articles. Research areas may include, but are not limited to, the following:

  • Alcohol-induced neurotoxicity;
  • Cocaine-induced neurotoxicity;
  • Methamphetamine-induced neurotoxicity;
  • Opioid-induced neurotoxicity;
  • Cannabis-induced neurotoxicity;
  • Cathinone-induced neurotoxicity;
  • Lysergic acid diethylamide (LSD)-induced neurotoxicity;
  • Ecstasy-induced neurotoxicity;
  • Electronic cigarette-induced neurotoxicity;
  • Drugs-of-abuse-induced liver toxicity and damage to other organs.

Prof. Dr. Youssef Sari
Guest Editor

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (10 papers)

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Research

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16 pages, 2296 KiB  
Article
Carbetocin Inhibits Behavioral Sensitization to Ethanol in Male and Female Mice, Independent of Corticosterone Levels
by Beatriz Yamada Costa, Luana Gasparini Santos, Priscila Marianno, Mariana Rae, Marina Gomes de Almeida, Malcon Carneiro de Brito, Rosângela Eichler and Rosana Camarini
Toxics 2023, 11(11), 893; https://doi.org/10.3390/toxics11110893 - 31 Oct 2023
Viewed by 1028
Abstract
Oxytocin (OXT), a pro-social peptide, is increasingly recognized as a potential protective substance against drug addiction. In the context of ethanol, previous research has shown OXT’s properties in reducing self-administration, alleviating motor impairment in rodents, and reducing craving in humans. However, its role [...] Read more.
Oxytocin (OXT), a pro-social peptide, is increasingly recognized as a potential protective substance against drug addiction. In the context of ethanol, previous research has shown OXT’s properties in reducing self-administration, alleviating motor impairment in rodents, and reducing craving in humans. However, its role in behavioral sensitization, a neuroadaptive response resulting from repeated drug exposure linked to an increased drug incentive, remains unexplored. OXT is recognized for its role in regulating the hypothalamic–pituitary–adrenal (HPA) axis, in which corticosterone is acknowledged as a significant factor in the development of behavioral sensitization. This study aimed to investigate the effects of carbetocin (CBT), an analogue of OXT, on the expression of behavioral sensitization to ethanol and the concurrent alterations in plasma corticosterone levels in male and female Swiss mice. We also aimed to confirm previous studies on OXT’s impact on ethanol consumption in male mice, but with a focus on CBT, using the two-bottle choice model and the drinking in the dark (DID) methodology. For the sensitization study, the mice received either ethanol (1.8 g/kg, i.p.) or saline treatments daily for 15 consecutive days, followed by treatment with carbetocin (0.64 mg/kg, i.p.) or a vehicle for 6 days. Subsequently, on day 22, all the animals underwent an ethanol challenge to assess the expression of behavioral sensitization. The plasma corticosterone levels were measured on days 21 and 22. The CBT effectively prevented the expression of ethanol-induced behavioral sensitization in both male and female subjects, with no alterations having been detected in their corticosterone levels. In the ethanol consumption study, following an initial phase of ethanol acquisition, the male mice underwent a 6-day treatment with CBT i.p. or saline before being re-exposed to ethanol. We also found a reduction in their ethanol consumption due to the CBT treatment. In conclusion, carbetocin emerges as a promising and effective intervention for mitigating ethanol-induced behavioral sensitization and reducing ethanol intake, highlighting its potential significance in alcohol addiction treatment. Full article
(This article belongs to the Special Issue Feature Papers in Drug Toxicity)
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14 pages, 2466 KiB  
Article
Effects of Chronic Hydrocodone Exposure and Ceftriaxone on the Expression of Astrocytic Glutamate Transporters in Mesocorticolimbic Brain Regions of C57/BL Mice
by Woonyen Wong and Youssef Sari
Toxics 2023, 11(10), 870; https://doi.org/10.3390/toxics11100870 - 20 Oct 2023
Cited by 1 | Viewed by 1033
Abstract
Exposure to opioids can lead to the alteration of several neurotransmitters. Among these neurotransmitters, glutamate is thought to be involved in opioid dependence. Glutamate neurotransmission is mainly regulated by astrocytic glutamate transporters such as glutamate transporter 1 (GLT-1) and cystine/glutamate antiporter (xCT). Our [...] Read more.
Exposure to opioids can lead to the alteration of several neurotransmitters. Among these neurotransmitters, glutamate is thought to be involved in opioid dependence. Glutamate neurotransmission is mainly regulated by astrocytic glutamate transporters such as glutamate transporter 1 (GLT-1) and cystine/glutamate antiporter (xCT). Our laboratory has shown that exposure to lower doses of hydrocodone reduced the expression of xCT in the nucleus accumbens (NAc) and the hippocampus. In the present study, we investigated the effects of chronic exposure to hydrocodone, and tested ceftriaxone as a GLT-1 upregulator in mesocorticolimbic brain regions such as the NAc, the amygdala (AMY), and the dorsomedial prefrontal cortex (dmPFC). Eight-week-old male mice were divided into three groups: (1) the saline vehicle control group; (2) the hydrocodone group; and (3) the hydrocodone + ceftriaxone group. Mice were injected with hydrocodone (10 mg/kg, i.p.) or saline for 14 days. On day seven, the hydrocodone/ceftriaxone group was injected with ceftriaxone (200 mg/kg, i.p.) for last seven days. Chronic exposure to hydrocodone reduced the expression of GLT-1, xCT, protein kinase B (AKT), extracellular signal-regulated kinases (ERK), and c-Jun N-terminal Kinase (JNK) in NAc, AMY, and dmPFC. However, hydrocodone exposure increased the expression of G-protein-coupled metabotropic glutamate receptors (mGluR5) in the NAc, AMY, and dmPFC. Importantly, ceftriaxone treatment normalized the expression of mGluR5, GLT-1, and xCT in all these brain regions, except for xCT in the AMY. Importantly, ceftriaxone treatment attenuated hydrocodone-induced downregulation of signaling pathways such as AKT, ERK, and JNK expression in the NAc, AMY, and dmPFC. These findings demonstrate that ceftriaxone has potential therapeutic effects in reversing hydrocodone-induced downregulation of GLT-1 and xCT in selected reward brain regions, and this might be mediated through the downstream kinase signaling pathways such as AKT, ERK, and JNK. Full article
(This article belongs to the Special Issue Feature Papers in Drug Toxicity)
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22 pages, 3258 KiB  
Article
Exploration of Tilmicosin Cardiotoxicity in Rats and the Protecting Role of the Rhodiola rosea Extract: Potential Roles of Cytokines, Antioxidant, Apoptotic, and Anti-Fibrotic Pathways
by Salwa A. Elgendy, Mohamed Mohamed Soliman, Heba I. Ghamry, Mustafa Shukry, Lina Abdelhady Mohammed, Hend Elsayed Nasr, Badriyah S. Alotaibi, Ibrahim Jafri, Samy Sayed, Amira Osman and Heba A. Elnoury
Toxics 2023, 11(10), 857; https://doi.org/10.3390/toxics11100857 - 13 Oct 2023
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Abstract
Tilmicosin (TIL) is a common macrolide antibiotic in veterinary medicine. High doses of TIL can have adverse cardiovascular effects. This study examined the effects of Rhodiola rosea (RHO) that have anti-inflammatory, antioxidant, and anti-fibrotic effects on tilmicosin (TIL)-induced cardiac injury targeting anti-inflammatory, antioxidant, [...] Read more.
Tilmicosin (TIL) is a common macrolide antibiotic in veterinary medicine. High doses of TIL can have adverse cardiovascular effects. This study examined the effects of Rhodiola rosea (RHO) that have anti-inflammatory, antioxidant, and anti-fibrotic effects on tilmicosin (TIL)-induced cardiac injury targeting anti-inflammatory, antioxidant, apoptotic, and anti-apoptotic signaling pathways with anti-fibrotic outcomes. Thirty-six male Wistar albino rats were randomly divided into groups of six rats each. Rats received saline as a negative control, CARV 1 mL orally (10 mg/kg BW), and RHO 1 mL orally at 400 mg/kg BW daily for 12 consecutive days. The TIL group once received a single subcutaneous injection (SC) dose of TIL (75 mg/kg BW) on the sixth day of the experiment to induce cardiac damage. The standard group (CARV + TIL) received CARV daily for 12 consecutive days with a single TIL SC injection 1 h after CARV administration only on the sixth day of study and continued for another six successive days on CARV. The protective group (RHO + TIL) received RHO daily for the same period as in CARV + TIL-treated rats and with the dosage mentioned before. Serum was extracted at the time of the rat’s scarification at 13 days of study and examined for biochemical assessments in serum lactate dehydrogenase (LDH), cardiac troponin I (cTI), and creatine phosphokinase (CK-MB). Protein carbonyl (PC) contents, malondialdehyde (MDA), and total antioxidant capacity (TAC) in cardiac homogenate were used to measure these oxidative stress markers. Quantitative RT-PCR was used to express interferon-gamma (INF-γ), cyclooxygenase-2 (COX-2), OGG1, BAX, caspase-3, B-cell lymphoma-2 (Bcl-2), and superoxide dismutase (SOD) genes in cardiac tissues, which are correlated with inflammation, antioxidants, and apoptosis. Alpha-smooth muscle actin (α-SMA), calmodulin (CaMKII), and other genes associated with Ca2+ hemostasis and fibrosis were examined using IHC analysis in cardiac cells (myocardium). TIL administration significantly increased the examined cardiac markers, LDH, cTI, and CK-MB. TIL administration also increased ROS, PC, and MDA while decreasing antioxidant activities (TAC and SOD mRNA) in cardiac tissues. Serum inflammatory cytokines and genes of inflammatory markers, DNA damage (INF-γ, COX-2), and apoptotic genes (caspase-3 and BAX) were upregulated with downregulation of the anti-apoptotic gene Bcl-2 as well as the DNA repair OGG1 in cardiac tissues. Furthermore, CaMKII and α-SMA genes were upregulated at cellular levels using cardiac tissue IHC analysis. On the contrary, pretreatment with RHO and CARV alone significantly decreased the cardiac injury markers induced by TIL, inflammatory and anti-inflammatory cytokines, and tissue oxidative-antioxidant parameters. INF-γ, COX-2, OGG1, BAX, and caspase-3 mRNA were downregulated, as observed by real-time PCR, while SOD and Bcl-2 mRNA were upregulated. Furthermore, the CaMKII and α-SMA genes’ immune reactivities were significantly decreased in the RHO-pretreated rats. Full article
(This article belongs to the Special Issue Feature Papers in Drug Toxicity)
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17 pages, 4271 KiB  
Article
Effects of Rosmarinus officinalis L. Extract on Neurobehavioral and Neurobiological Changes in Male Rats with Pentylenetetrazol-Induced Epilepsy
by Jawaher Alrashdi, Gadah Albasher, Mohammed M. Alanazi, Wedad Saeed Al-Qahtani, Abdulkareem A. Alanezi and Fawaz Alasmari
Toxics 2023, 11(10), 826; https://doi.org/10.3390/toxics11100826 - 30 Sep 2023
Cited by 2 | Viewed by 1228
Abstract
This study investigated the effect of Rosmarinus officinalis L. (RO) extract on neurobehavioral and neurobiological changes in male rats with pentylenetetrazol (PTZ)-induced epilepsy. Rats were assigned into five groups: (1) control rats, (2) RO-treated rats, (3) PTZ-treated rats, (4) PTZ + RO-treated rats, [...] Read more.
This study investigated the effect of Rosmarinus officinalis L. (RO) extract on neurobehavioral and neurobiological changes in male rats with pentylenetetrazol (PTZ)-induced epilepsy. Rats were assigned into five groups: (1) control rats, (2) RO-treated rats, (3) PTZ-treated rats, (4) PTZ + RO-treated rats, and (5) PTZ + valproic acid (VA)-treated rats. The PTZ-treated rats required a significantly longer time and distance to find the platform in the Morris water maze test than the control and RO-treated rats. Additionally, PTZ-treated rats showed a decrease in tendency to cross over the platform compared to PTZ group. PTZ + RO-treated rats showed decreased swimming time and distance to find the platform compared to PTZ group. PTZ + RO-treated rats showed a significant decrease in seizure score, a reduced number of myoclonic jerks, and an increased onset of the first myoclonic jerk compared to PTZ group. PTZ reduced the time required to enter the dark room in the passive avoidance learning test, which was reversed by RO treatment. Biochemical results revealed that PTZ-treated rats had higher levels of oxidative stress markers. RO significantly increased the antioxidant markers levels and maintained normal rat brain histology. This study revealed that RO can shield the brain and neural tissues from PTZ. Full article
(This article belongs to the Special Issue Feature Papers in Drug Toxicity)
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15 pages, 2276 KiB  
Article
Mechanistic Assessment of Anise Seeds and Clove Buds against the Neurotoxicity Caused by Metronidazole in Rats: Possible Role of Antioxidants, Neurotransmitters, and Cytokines
by Amira M. El-Moslemany, Mai Hussein Abd-Elfatah, Nawal A. Tahoon, Rasha M. Bahnasy, Badriyah S. Alotaibi, Heba I. Ghamry and Mustafa Shukry
Toxics 2023, 11(9), 724; https://doi.org/10.3390/toxics11090724 - 24 Aug 2023
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Abstract
Long-term use of the nitroimidazole-derived antibiotic metronidazole has been associated with neuronal damage due to its ability to cross the blood–brain barrier. Polyphenol-rich plants, such as anise seeds and clove buds, are suggested to have neuroprotective effects. However, their intracellular protective pathway against [...] Read more.
Long-term use of the nitroimidazole-derived antibiotic metronidazole has been associated with neuronal damage due to its ability to cross the blood–brain barrier. Polyphenol-rich plants, such as anise seeds and clove buds, are suggested to have neuroprotective effects. However, their intracellular protective pathway against metronidazole-induced neurotoxicity remains unexplored. This study aims to evaluate the potential neuroprotective benefits of anise seeds and clove buds and elucidate the proposed metronidazole-induced neurotoxicity mechanism. This study divided rats into six groups, each containing six rats. In Group I, the control group, rats were administered saline orally. Group II rats received 200 mg/kg of metronidazole orally. Group III rats received 250 mg/kg b.w. of anise seed extract and metronidazole. Group IV rats received 500 mg/kg b.w. of anise seed extract (administered orally) and metronidazole. Group V rats received 250 mg/kg b.w. of clove bud extract (administered orally) and metronidazole. Group VI rats were administered 500 mg/kg b.w. of clove bud extract and metronidazole daily for 30 consecutive days. The study evaluated the phenolic compounds of anise seeds and clove buds. Moreover, it assessed the inflammatory and antioxidant indicators and neurotransmitter activity in brain tissues. A histological examination of the brain tissues was conducted to identify neuronal degeneration, brain antioxidants, and apoptotic mRNA expression. The study found that metronidazole treatment significantly altered antioxidant levels, inflammatory mediators, and structural changes in brain tissue. Metronidazole also induced apoptosis in brain tissue and escalated the levels of inflammatory cytokines. Oral administration of metronidazole resulted in a decrease in GABA, dopamine, and serotonin and an increase in ACHE in brain tissue. Conversely, oral administration of anise and clove extracts mitigated the harmful effects of metronidazole. The neurotoxic effects of metronidazole appear to stem from its ability to reduce antioxidants in brain tissue and increase nitric oxide production and apoptosis. The study concludes that neuronal damage caused by metronidazole is significantly mitigated by treatment with anise and clove extracts. Full article
(This article belongs to the Special Issue Feature Papers in Drug Toxicity)
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20 pages, 5090 KiB  
Article
Time- and Concentration-Dependent Adverse Effects of Paclitaxel on Non-Neuronal Cells in Rat Primary Dorsal Root Ganglia
by Amira Elfarnawany and Faramarz Dehghani
Toxics 2023, 11(7), 581; https://doi.org/10.3390/toxics11070581 - 04 Jul 2023
Viewed by 1801
Abstract
Paclitaxel is a chemotherapeutic agent used to treat a wide range of malignant tumors. Although it has anti-tumoral properties, paclitaxel also shows significant adverse effects on the peripheral nervous system, causing peripheral neuropathy. Paclitaxel has previously been shown to exert direct neurotoxic effects [...] Read more.
Paclitaxel is a chemotherapeutic agent used to treat a wide range of malignant tumors. Although it has anti-tumoral properties, paclitaxel also shows significant adverse effects on the peripheral nervous system, causing peripheral neuropathy. Paclitaxel has previously been shown to exert direct neurotoxic effects on primary DRG neurons. However, little is known about paclitaxel’s effects on non-neuronal DRG cells. They provide mechanical and metabolic support and influence neuronal signaling. In the present study, paclitaxel effects on primary DRG non-neuronal cells were analyzed and their concentration or/and time dependence investigated. DRGs of Wister rats (6–8 weeks old) were isolated, and non-neuronal cell populations were separated by the density gradient centrifugation method. Different concentrations of Paclitaxel (0.01 µM–10 µM) were tested on cell viability by MTT assay, cell death by lactate dehydrogenase (LDH) assay, and propidium iodide (PI) assay, as well as cell proliferation by Bromodeoxyuridine (BrdU) assay at 24 h, 48 h, and 72 h post-treatment. Furthermore, phenotypic effects have been investigated by using immunofluorescence techniques. Paclitaxel exhibited several toxicological effects on non-neuronal cells, including a reduction in cell viability, an increase in cell death, and an inhibition of cell proliferation. These effects were concentration- and time-dependent. Cellular and nuclear changes such as shrinkage, swelling of cell bodies, nuclear condensation, chromatin fragmentation, retraction, and a loss in processes were observed. Paclitaxel showed adverse effects on primary DRG non-neuronal cells, which might have adverse functional consequences on sensory neurons of the DRG, asking for consideration in the management of peripheral neuropathy. Full article
(This article belongs to the Special Issue Feature Papers in Drug Toxicity)
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17 pages, 2565 KiB  
Article
Natural Polyphenols—Resveratrol, Quercetin, Magnolol, and β-Catechin—Block Certain Aspects of Heroin Addiction and Modulate Striatal IL-6 and TNF-α
by Shaimaa ElShebiney, Rania Elgohary, Marwa El-Shamarka, Noha Mowaad and Osama A. Abulseoud
Toxics 2023, 11(4), 379; https://doi.org/10.3390/toxics11040379 - 17 Apr 2023
Cited by 1 | Viewed by 1662
Abstract
We have examined the effects of four different polyphenols in attenuating heroin addiction using a conditioned place preference (CPP) paradigm. Adult male Sprague Dawley rats received heroin (alternating with saline) in escalating doses starting from 10 mg/kg, i.p. up to 80 mg/kg/d for [...] Read more.
We have examined the effects of four different polyphenols in attenuating heroin addiction using a conditioned place preference (CPP) paradigm. Adult male Sprague Dawley rats received heroin (alternating with saline) in escalating doses starting from 10 mg/kg, i.p. up to 80 mg/kg/d for 14 consecutive days. The rats were treated with distilled water (1 mL), quercetin (50 mg/kg/d), β-catechin (100 mg/kg/d), resveratrol (30 mg/kg/d), or magnolol (50 mg/kg/d) through oral gavage for 7 consecutive days, 30 min before heroin administration, starting on day 8. Heroin withdrawal manifestations were assessed 24 h post last heroin administration following the administration of naloxone (1 mg/kg i.p). Heroin CPP reinstatement was tested following a single dose of heroin (10 mg/kg i.p.) administration. Striatal interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) were quantified (ELISA) after naloxone-precipitated heroin withdrawal. Compared to the vehicle, the heroin-administered rats spent significantly more time in the heroin-paired chamber (p < 0.0001). Concomitant administration of resveratrol and quercetin prevented the acquisition of heroin CPP, while resveratrol, quercetin, and magnolol blocked heroin-triggered reinstatement. Magnolol, quercetin, and β-catechin blocked naloxone-precipitated heroin withdrawal and increased striatal IL-6 concentration (p < 0.01). Resveratrol administration was associated with significantly higher withdrawal scores compared to those of the control animals (p < 0.0001). The results of this study show that different polyphenols target specific behavioral domains of heroin addiction in a CPP model and modulate the increase in striatal inflammatory cytokines TNF-α and IL-6 observed during naloxone-precipitated heroin withdrawal. Further research is needed to study the clinical utility of polyphenols and to investigate the intriguing finding that resveratrol enhances, rather than attenuates naloxone-precipitated heroin withdrawal. Full article
(This article belongs to the Special Issue Feature Papers in Drug Toxicity)
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15 pages, 2638 KiB  
Article
The Role of Vitamin E in Protecting against Oxidative Stress, Inflammation, and the Neurotoxic Effects of Acute Paracetamol in Pregnant Female Rats
by Alaa M. Hammad, Baraa Shawaqfeh, Suhair Hikmat, Tariq Al-Qirim, Lama Hamadneh, Sameer Al-Kouz, Mariam M. Awad and Frank S. Hall
Toxics 2023, 11(4), 368; https://doi.org/10.3390/toxics11040368 - 12 Apr 2023
Viewed by 1784
Abstract
Paracetamol (acetaminophen, APAP) is the most common non-prescription analgesic drug used during pregnancy. The aim of this study was to investigate the effect of vitamin E on acute APAP toxicity in pregnant rats. Toxicity in the liver, kidney, and brain (hippocampus, cerebellum, and [...] Read more.
Paracetamol (acetaminophen, APAP) is the most common non-prescription analgesic drug used during pregnancy. The aim of this study was to investigate the effect of vitamin E on acute APAP toxicity in pregnant rats. Toxicity in the liver, kidney, and brain (hippocampus, cerebellum, and olfactory bulb) was examined. Twenty pregnant female Wistar rats at gestational day 18 were used. Pregnant rats were divided into four groups: Control, APAP, E + APAP, and APAP + E. The Control group was treated with 0.5 mL p.o. corn oil. The APAP group received 3000 mg/kg p.o. APAP. The E + APAP group received 300 mg/kg p.o. vitamin E one hour before 3000 mg/kg APAP. The APAP + E group received 3000 mg/kg paracetamol one hour before 300 mg/kg p.o. vitamin E. Twenty-four hours after the last treatment administration, rats were euthanized and blood, brain, liver, and kidney samples were collected. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine levels, uric acid (UA), and superoxide dismutase (SOD) levels, as well as the relative mRNA expression of Cyp1a4, Cyp2d6, and Nat2, were determined. Acute APAP treatment upregulated ALT, AST, BUN, and creatinine levels. APAP treatment downregulated UA and SOD levels. APAP treatment upregulated the relative mRNA expression of Cyp1a4 and Cyp2d6, but downregulated Nat2 expression. Vitamin E treatment, either before or after APAP administration, attenuated the toxic effects of APAP. In conclusion, the results showed that an acute toxic APAP dose in late pregnancy can cause oxidative stress and dysregulation in Cyp isoform expression, and that vitamin E treatment attenuates these effects. Full article
(This article belongs to the Special Issue Feature Papers in Drug Toxicity)
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18 pages, 9465 KiB  
Article
Exploration of Maternal and Fetal Toxicity Risks for Metronidazole-Related Teratogenicity and Hepatotoxicity through an Assessment in Albino Rats
by Mervat A. AbdRabou, Barakat M. Alrashdi, Hadeel K. Alruwaili, Reda H. Elmazoudy, Maha A. Alwaili, Sarah I. Othman, Fawzyah A. Alghamdi and Gehan H. Fahmy
Toxics 2023, 11(4), 303; https://doi.org/10.3390/toxics11040303 - 25 Mar 2023
Cited by 2 | Viewed by 5229
Abstract
Metronidazole is the primary antimicrobial drug for treating acute and chronic vaginal pathogens during pregnancy; however, there has been insufficient research on placental disorders, early pregnancy loss, and preterm birth. Here, the potential activity of metronidazole on pregnancy outcomes was investigated. 130 mg/kg [...] Read more.
Metronidazole is the primary antimicrobial drug for treating acute and chronic vaginal pathogens during pregnancy; however, there has been insufficient research on placental disorders, early pregnancy loss, and preterm birth. Here, the potential activity of metronidazole on pregnancy outcomes was investigated. 130 mg/kg body weight of metronidazole was orally given individually to pregnant rats on gestation days 0–7, 7–14, and 0–20. Pregnancy outcome evaluations were carried out on gestation day 20. It was demonstrated that metronidazole could induce maternal and fetal hepatotoxicity. There is a significant increase in the activities of maternal hepatic enzymes (ALT, AST, and ALP), total cholesterol, and triglycerides compared with the control. These biochemical findings were evidenced by maternal and fetal liver histopathological alterations. Furthermore, metronidazole caused a significant decrease in the number of implantation sites and fetal viability, whereas it caused an increase in fetal lethality and the number of fetal resorptions. In addition, a significant decrease in fetal weight, placental weight, and placental diameter was estimated. Macroscopical examination revealed placental discoloration and hypotrophy in the labyrinth zone and the degeneration of the basal zone. The fetal defects are related to exencephaly, visceral hernias, and tail defects. These findings suggest that the administration of metroniazole during gestation interferes with embryonic implantation and fetal organogenesis and enhances placental pathology. We can also conclude that metronidazole has potential maternal and fetal risks and is unsafe during pregnancy. Additionally, it should be strictly advised and prescribed, and further consideration should be given to the associated health risks. Full article
(This article belongs to the Special Issue Feature Papers in Drug Toxicity)
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12 pages, 298 KiB  
Review
Xylazine Poisoning in Clinical and Forensic Practice: Analysis Method, Characteristics, Mechanism and Future Challenges
by Tingting Mai, Youyou Zhang and Shuquan Zhao
Toxics 2023, 11(12), 1012; https://doi.org/10.3390/toxics11121012 - 11 Dec 2023
Viewed by 1516
Abstract
Xylazine abuse is emerging globally, while the identification of xylazine lethal cases poses a great challenge in clinical and forensic practice. The non-specific symptoms delay the diagnosis and treatment of xylazine poisoning, the pathological changes and lethal concentration of xylazine in body fluid [...] Read more.
Xylazine abuse is emerging globally, while the identification of xylazine lethal cases poses a great challenge in clinical and forensic practice. The non-specific symptoms delay the diagnosis and treatment of xylazine poisoning, the pathological changes and lethal concentration of xylazine in body fluid and organs of fatal xylazine poisoning cases are seldom reported and the other toxins detected in such cases complicate the role of xylazine in the cause of death. Therefore, we carefully reviewed related updated information on xylazine, summarized the knowledge from clinical and forensic perspectives and can thus provide a reference in such cases and throw light on further study in the field of xylazine poisoning. Full article
(This article belongs to the Special Issue Feature Papers in Drug Toxicity)
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