Journal of Toxicology最新文献

The increasing popularity of herbal preparations has prompted people around the world to incorporate herbal products into their balanced diet, aiming to improve brain health and protect against neurological disorders. Erqember(Erq-Em) possesses a blend of various neuroprotective phytocompounds. The present study aimed to phytochemically analyze this polyherbal product and scientifically validate its neurological benefits. After chemical characterization through UHPLC-MS, in vivo studies involved the supplementation of mice with 10 and 20 mL/kg doses of Erq-Em in an AlCl₃-induced amnesic mice model followed by behavioral assessment for anxiety and cognition in a battery of behavioral tests. Subsequently, whole brains were dissected for biochemical and histopathological analysis. Further, the study also included in silico studies to understand the interaction of detected phytocompounds with acetylcholinesterase protein. The outcomes revealed that mice treated with Eqr-Em were protected from anxiety-like behavior as they dose-dependently prefer innately frightening central, lightened, and elevated zones in OFT, L/D, and EPM tests. Moreover, the Erq-Em supplementation caused improved spontaneous learning in Y-maze and NOR tests, while their memory in passive avoidance and water maze tests was evident from longer step-through and shorter escape latencies, respectively. The biochemical analysis of brain homogenates showed a reduction in AchE and MDA while elevation in SOD and GPx levels in mice receiving Erq-Em. Moreover, the healthy and intact neuronal counts were markedly high in CA1 and DG regions of Nissl's-stained hippocampi of Erq-Em-treated mice. The compounds detected by UPLC-MS showed favorable BBB permeability and interacted well with acetylcholinesterase protein through in silico studies. Overall, the neurological benefits of Erqember might result from enhanced cholinergic neurotransmission and antioxidative activity of its phytocompounds, which together function as multimodal strategies against AlCl₃-induced neurotoxicity.

Clarias gariepinus' (Burchell, 1822) early-stage development was assessed in microconcentrations of glyphosate-based herbicides (GBHs), Forceup, Roundup, and Uproot. Using the default ecological trigger value of 0.37 mg L^-1 of glyphosate as a reference, herbicides were diluted to microconcentrations containing 0.006, 0.013, 0.025, 0.05, and 0.10 ([v/v] %) of herbicide using borehole water, which served as control. Concentrations and control were replicated three times. Fertilization (%), time to morula formation and to commencement of hatching (minutes), hatching (% fertilized eggs), and 96-h larval survival (% hatched larvae) in microconcentrations were monitored. Within formulation, concentration significantly affected fertilization and hatching rates (p < 0.001), time to morula formation and hatching, and 96-h larval survival ([χ ²] 5 = 16,648, p = 0.010; [Kruskal-Wallis H test]). Morula formation, fertilization, hatching, and larval survival rates were significantly affected by formulation in Concentrations 2 and 3, while fertilization rate was significantly affected at all concentrations ([χ ²] 3 = 6.49, p = 0.039). The glyphosate ecological trigger value of 0.37 mg L^-1 as well as the recommended application rate of Roundup Proactive in aquatic and riparian environments of 0.32% (v/v) are higher than the lowest significant effect concentrations of the herbicides. Reactive oxygen species (ROS) and superoxide dismutase (SOD) in control embryos, were higher but not significantly, than levels in freshly stripped eggs (p > 0.05) (Mann-Whitney U test). Early-stage development was normal in controls, suggesting a balance between ROS and SOD. This was, however upset in treatments, leading to deleterious effects on early-stage development. GBHs pose a greater risk to fish reproduction, varying in severity with the formulation. This should be considered in regulations for their use in aquatic and riparian environments, balancing herbicide effectiveness with the risk of aquatic toxicity.

Following our research on intoxication cases in Morocco, we conducted an investigation into intoxications in the Fez-Meknes region, one of the 12 regions in Morocco most affected by this problem. The main aim of this study is to report the characteristics of intoxication cases and their management. We deemed it necessary to carry out this study to identify the specificities of the Fez-Meknes region and subsequently propose specific measures to minimize risks. Our registry data were based on intoxication cases reported between 1999 and 2018 by the Poison and Pharmacovigilance Center of Morocco (PPCM). During the study period, 23,550 cases were collected. The median age of the patients was 20 years, with extremes ranging from 1 day to 98 years. The sex ratio (M/F) was 0.67. Gaseous compounds were the most incriminated products, accounting for 36.6% of cases. Among the 18,192 patients with a known outcome, 242 cases resulted in death, representing a case fatality rate of 1.3%. The findings of this work provide the first contributions to current data on the epidemiology of intoxications in the Fez-Meknes region over the last 20 years. These data show that intoxications are frequent and of moderate severity.

Purpose: Gastrointestinal mucositis (GI-M) is the most common adverse effect of methotrexate (MTX). Gallic acid (GA) is a polyphenolic component rich in green tea, gall nuts, hops, grapes, and oak bark and has anti-inflammatory and antioxidant properties. The aim was to investigate the impact of GA on proinflammatory cytokines, expression level of hepatocyte growth factor (HGF) and C-met genes, and histopathological alterations of MTX-induced GI-M in rats. Methods: Twenty-four male Wistar rats were randomly divided into four groups: control, GA, MTX, and MTX + GA. Mucositis was induced in the experimental groups (MTX and MTX + GA) through three intradermal injections (the third to fifth days) of 2.5 mg/kg MTX in the suprascapular region. The GA group received 100 mg/kg GA via gavage, while the control group received normal saline by gavage (7 continuous days) and via intradermal injection (the third to fifth days) in the suprascapular region. The intestinal jejunal tissue and serum were analyzed for HGF and C-met mRNA expression, as well as levels of tumor necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β). In addition, a histopathological study was to eperformedvaluate the villi of mucosa and fibrosis of submucosal layers. Results: Decreased levels of HGF and C-met gene expression in the MTX group were significantly increased by GA administration (p < 0.05). GA administration decreased the elevated levels of TNF-α and IL-1β (p < 0.001) in the MTX group. Histopathological findings showed an adverse effect of MTX in mucosa which was relatively ameliorated in the MTX + GA ones. Conclusion: GA could increase HGF and C-met expression, decrease inflammatory cytokines, and improve histological injuries, affected by MTX, indicating a beneficial role for GA following GI-M.

Atrazine is an herbicide associated with respiratory disorders and the presence of oxidative stress, which can be reversed by association with antioxidant compounds, such as vitamin E. This study aimed to investigate the impact of atrazine (AZ) on the male rat diaphragm muscle and the attenuating effects of vitamin E. Fifty-two male rats were received for 28 days by gavage (n = 13/group): C (control), corn oil; AZ (100 mg/kg); AZE, AZ (100 mg/kg) and vitamin E (200 mg/kg); E, vitamin E (200 mg/kg). Both oxidative stress analysis and morphological analysis of the diaphragm muscle, neuromuscular junction (NMJ), and phrenic nerve were performed. Exposure to AZ caused oxidative stress in muscle fibers, as evidenced by the highest lipid hydroperoxide, and hydrophilic antioxidant capacity values in the AZ group. However, in the AZE group, these values were like those of the C group. The area and diameter of the muscle fiber were only larger in the E group. Exposure to AZ caused oxidative stress in the diaphragm muscle, but vitamin E attenuated these alterations and protected muscle fibers from the oxidative damage. Therefore, vitamin E may serve as a useful attenuating agent against AZ-induced oxidative stress in the skeletal muscle.

Background: The safety of combining tamsulosin (an allopathic drug) and Croton membranaceus aqueous extract, a medicinal plant for managing benign prostatic hyperplasia (BPH), was investigated. Methods: The roots of CM were used and processed into a water extract by maceration and decoction. Thirty-five Sprague Dawley rats were divided into seven groups of five rats each. Groups 2-7 were orchidectomy/testosterone injections BPH-induced. Group 1 was designated as the control group. Group 2 was designated as the model group (untreated). Group 3 was treated with 0.03 mg/kg b.wt. of tamsulosin. Group 4 received 30 mg/kg b.wt. of CM (low dose [LD]). Group 5 received 300 mg/kg b.wt. of CM (high dose [HD]); Group 6 received 0.03 mg/kg b.wt. of tamsulosin plus 30 mg/kg b.wt. of CM. Group 7 received 0.03 mg/kg b.wt. plus 300 mg/kg b.wt. of CM. Tamsulosin and CM were administered by oral gavage for 28 days. Prostate-specific antigen (PSA) levels, renal and liver function tests, and histology were assessed. Results: PSA decreased after treatment with LD CM (0.44 ± 0.03 ng/mL) and tamsulosin (0.43 ± 0.04 ng/mL) combined, compared with the control group (0.63 ± 0.03 ng/mL) (p < 0.006). Prostate gland/accessory organ weights were as follows: tamsulosin < CM LD < CM HD/T < CM LD/T < CM HD < model. In the CM LD/T group, the acini appeared empty and the acini fluid contained fatty droplets with a slender outer boundary that had very little active mucous surface. At a higher dose, CM HD/T caused a reduction in the sizes and shapes of active acini with most being empty and having little active mucous surfaces. Conclusion: The results suggest that the combination of C. membranaceus and tamsulosin does not provide additional therapeutic benefits for treating BPH. Relative organ weights provide a better evaluation metric than total organ weights.

Background: The synergistic activity of compounds in herbal drugs has been well established by multiple scientific studies. The compounds present in plants may have increased toxicity and increased efficacy. Owing to the notion that traditional medicines do not have any adverse effects, these are used heftily. Aim: The present study was designed to assess the toxicity of an herbal drug consisting of Asparagus racemosus roots, Tinospora cordifolia stems, and Trigonella foenum-graecum seeds extract blend (ATTEB), which is widely employed as an antimicrobial, anti-inflammatory, immunomodulator, adaptogen, female tonic, galactagogue, etc. Methodology: The current study evaluated its safety by acute (OECD 423) and subacute (OECD 407) repeated-dose toxicity studies. A phytochemical investigation was carried out and revealed the presence of principal bioactive constituents. A genotoxicity study was performed by micronucleus assay. Gross necroscopy of the animals was performed, and behavioral, hematological, biochemical, and histopathological studies were performed. Results: In the acute toxicity study, there was no mortality and no significant changes in behavior, organ structure, or organ weight, as observed by gross necroscopy of the animals, at a single dose of 2000 mg/kg BW. In a 28-day repeated-dose toxicity study, up to a daily dose of 1000 mg/kg BW, there was no evidence of toxicity. No significant genotoxicity was observed in the mice. Conclusion: The LD₅₀ found to be greater than 2000 mg/kg BW with NOAEL at 1000 mg/kg BW in mice. It was found to be free from any genotoxicity. The herbal drug was found to be safe to level of category 4 and can be used further for clinical studies.

Background: Drug poisoning is the most common type of poisoning in the world. The utilization of tramadol for the management of pain has been identified as a significant contributor to the incidence of poisoning cases. Tramadol poisoning can result in a range of neurological complications, including seizures and a decreased level of consciousness. Tramadol-induced seizures are frequently dose independent and manifest as generalized tonic-clonic seizures. The neurotoxic effects of tramadol are primarily manifested within the initial 24 h period following ingestion, with 84.6% of the seizures occurring within the first six hours. In addition, it has been documented that 15%-35% of the patients with tramadol poisoning have experienced seizures. The present study was undertaken to elucidate the clinical and paraclinical signs and symptoms observed in patients with tramadol poisoning and their correlation with the occurrence of seizures. Methods and Materials: All patients hospitalized due to tramadol poisoning from October 2019 to September 2020 in the poisoning department of Imam Reza Hospital if they met the inclusion criteria were studied. The patients were divided into two groups with and without seizures. The occurrence of seizures was substantiated through the documentation of EMS personnel and the direct observation of the attending physician in the emergency room. Following admission, the patient's blood glucose level was quantified via a glucometer. A blood sample was also obtained for subsequent laboratory evaluation. In the event of any aberrations in blood glucose levels, a re-evaluation was conducted at one-hour intervals using a glucometer. All findings were analyzed using SPSS Version 25 statistical software. The level of significance was set at p < 0.05. Results: A total of 163 patients were included in this study. In 94 patients (57.3%), some degree of consciousness loss and seizures occurred in 69 patients (42.1%). There was a significant relationship between the occurrence of seizures and the increase in blood glucose levels of patients (p=0.031). The findings indicated that 60% of the patients with blood glucose levels exceeding 140 mg/dL experienced seizures. Conclusion: Seizures in tramadol poisoning may be related to the patient's blood glucose levels.

The environmental xenobiotic aluminum chloride (AlCl₃) destroys reproduction via free radicals. The present study aimed at evaluating the impact of purple and white eggplant on rat fertility when exposed to AlCl₃. A total of 36 male albino rats were divided into six groups: a negative control, the second given AlCl₃ (17 mg/kg b.w.) for 28 days, the third and fourth given a basal diet with 5% and 10% white eggplant powder, and the fifth and sixth given a basal diet with 5% and 10% purple eggplant powder. AlCl₃ reduced follicular-stimulating hormone (FSH), plasma testosterone, sperm count, motility, and viability, luteinizing hormone (LH), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) activities. On the contrary, malondialdehyde (MDA) and tumor necrosis factor alpha (TNF-α) disclosed considerable increases. Besides, reproductive hormones, antioxidant enzymes, and sperm quality were significantly enhanced in the treated groups with eggplants. A downregulation in the expression of Fkbp6, Ccna1, and Cyp19A1 was detected, and normal expression was restored after treatment with high dose from eggplant (10%) without significant differences, whereas Msh4 and Cdk2 genes continued in their down expression and measured decrease up to 60% in Msh4 and 40% in Cdk2 in their mRNA levels after treatment with high dosage from eggplant, respectively. Alternatively, rats treated with eggplant at high dose (10%) gained more body weight (33%) and much bigger testicles (1.30 ± 0.05 g) when compared to AlCl₃-treated rats (gained only 16% more body weight and 1.04 ± 0.06 g testis weight) after 28 days, subsequently, the eggplant reduced the side effect of AlCl3-induced toxicity. AlCl₃ induced broad cytotoxic effects in seminiferous tubules, and the antioxidant and anti-inflammatory activities of eggplant minimized the histological alteration in rat testes.

Background: Crude oil, a major key economic driver in developing countries, is also of environmental concern, linked to neurotoxicity and behavioural problems. Despite the known neurotoxic effects of crude oil and the potential benefits of zinc and vitamin E, there is a paucity of research specifically addressing their combined efficacy in mitigating neurochemical changes and behavioural deficits induced by crude oil. Current studies have largely focussed on the individual effects of these supplements in different contexts, but their synergistic potential in a crude oil exposure model remains underexplored. This study investigated the potential effects of zinc and vitamin E on neurobehavioural alterations in male Wistar rats fed with Bonny light crude oil (BLCO)-contaminated diet. Methods: Thirty (30) male Wistar rats (160 ± 10 g) were assigned into five groups (n = 6). Group 1 received standard rat feed, Group 2 was exposed to BLCO (0.1 mL/g of rat feed) for 3 weeks, and groups 3-5 were treated with zinc (50 mg/kg/day), vitamin E (400 IU/kg), or both [vitamin E (400 IU/kg) + zinc (50 mg/kg/day)], respectively for 1 week after BLCO exposure for 3 weeks. Locomotive, anxiolytic, depressive-like behaviours and spatial memory were assessed using the open-field test, elevated plus maze, forced swim test and Y-maze. Rats were sacrificed and the brain samples were collected for biochemical assays at the end of the behavioural tests. Results: Zinc and vitamin E supplementation (individually or combined) significantly increased brain total antioxidant capacity and superoxide dismutase (SOD) activity, reduced inflammatory markers (TNF-alpha) and lipid peroxidation, normalized neurotransmitter levels in the brain and improved behavioural performance. Conclusion: Treatment with Zn and/or vitamin E reverses BLCO-induced neurobehavioural alterations via modulation of oxidative stress, inflammation and neurotransmitters.