Journal of Toxicology最新文献

Chemotherapeutic agents are pivotal in cancer management, yet their utility is constrained by pronounced systemic and organ-specific toxicity, necessitating rigorous preclinical evaluation to enhance their safe application in oncology. This study examined the hematological, biochemical, electrolyte, and histopathological effects of seven chemotherapeutic drugs-docetaxel (10 mg/kg body weight), doxorubicin (10 mg/kg), paclitaxel (4 mg/kg), oxaliplatin (4 mg/kg), cisplatin (2 mg/kg), cytarabine (50 mg/kg), and cyclophosphamide (10 mg/kg)-and a phosphate-buffered saline (PBS) control (10 mL/kg) in male Wistar rats (n = 40, eight groups of five), adhering to the Organization for Economic Co-operation and Development (OECD) Guideline 425. Doses were selected based on established protocols from prior studies. Docetaxel induced leukocytosis and thrombocytosis, whereas doxorubicin and cisplatin elicited leukopenia and lymphopenia. Biochemical profiling revealed hepatotoxicity (elevated aminotransferase, alkaline phosphatase, and bilirubin) in rats treated with paclitaxel and cytarabine and nephrotoxicity (increased urea and creatinine) in those receiving paclitaxel and cyclophosphamide. Electrolyte analysis indicated hyperkaliemia with oxaliplatin, contrasted by hypokalemia with doxorubicin and cisplatin. Histopathological assessment of liver, kidney, spleen, and stomach tissues, stained with hematoxylin and eosin (H and E), revealed subacute, organ-specific alterations in rats administered cytarabine (50 mg/kg), cisplatin (2 mg/kg), doxorubicin (10 mg/kg), and cyclophosphamide (10 mg/kg) compared to the control (10 mL/kg), especially liver vacuolation and sinusoidal narrowing, kidney tubular flattening and glomerular compaction, spleen white pulp hypocellularity with red pulp congestion, and stomach submucosal inflammation with glandular hyperplasia. Notably, no necrosis or fibrosis was observed, suggesting potentially reversible effects. These findings highlight the heterogeneous toxicity profiles of chemotherapeutic agents, advocating for personalized monitoring and protective strategies in clinical practice to optimize therapeutic safety and efficacy.

Introduction: Acute kidney injury represents a spectrum of diseases and is one of the most common threats to global public health. Gentamicin is the most common nephrotoxic antibiotic drug. Consequently, there is an urgent need to identify effective and safe therapeutic options from medicinal plants. Therefore, the purpose of this in vivo study is to evaluate the nephroprotective effects of the root of Rumex abyssinicus Jacq in Swiss albino mice exposed to gentamicin toxicity.

Methods: A total of 30 mice were divided into five groups of six mice each. It comprised a normal control group (Group I) that received distilled water orally, Group II (100 mg/kg gentamicin-induced) without any intervention, and Group III-V that were experimental groups induced with 100 mg/kg gentamicin and treated with extracts of Rumex abyssinicus at the dose of 100, 200, and 400 mg/kg daily for 14 days. Blood and kidney tissues were taken for biochemistry and histological analysis on the fifteenth day.

Result: Rumex abyssinicus extract treatment provided a significant nephroprotective effect (p < 0.001) against gentamicin-induced toxicity, as indicated by increased body weight and reduced kidney weight. In mice given 200 and 400 mg/kg of extract, the creatinine, urea, and uric acid measurements were decreased significantly compared to Group II. Furthermore, a similar dose of extracts showed the prevention of kidney damage via reduced tubular necrosis, glomerular congestion, and mononuclear infiltration, compared to the negative control, whereas mice given at the dose of 100 mg/kg extract showed no difference compared with Group II.

Conclusion: This study explained that the extracts of Rumex abyssinicus might act as a potent free radical scavenger and restore the toxic effects of gentamicin and a potential nephroprotective agent.

Quercetagetin is a flavonoid that has shown antiproliferative effects against different human cancers. We thoroughly analysed the effects of quercetagetin obtained from Tagetes erecta on human triple-negative breast cancer cells (MDA-MB-231) and murine breast cancer cells (JC) to elucidate its underlying antineoplastic mechanisms. Quercetagetin exerted dose-dependent antiproliferative effects on both cell lines (half-maximal inhibitory concentration: 188 and 282 μM, respectively). While it eliminated MDA-MB-231 cells via both apoptosis and autophagy, it predominantly eliminated JC cells via ferroptosis. Our results demonstrate that quercetagetin induces different programmed cell death pathways in a species-specific manner. Notably, quercetagetin did not significantly affect the proliferation of noncancerous lymphocytic cells. These data may facilitate the development of anticancer drugs that induce programmed cell death with fewer side effects.

Background: Latin America and the Caribbean (LAC), a region of critical biodiversity and natural resources, faces escalating threats from anthropogenic soil and water pollution. While individual studies have documented contamination, a comprehensive synthesis of its impacts on ecosystems and public health across the region was lacking.

Objective: This systematic review aimed to map and qualitatively synthesize the empirical evidence on the impacts of soil and water pollution in LAC, identifying regional research trends and critical knowledge gaps.

Methods: A systematic search was conducted across five databases (EBSCOhost, PubMed, SciELO, JSTOR, and HINARI) for peer-reviewed literature (2008-2023). Following a blinded, two-phase screening of 1145 records via Rayyan software, 11 studies met the predefined inclusion criteria for qualitative synthesis. Data on geographic context, pollutant profiles, exposure assessment, and health/ecological endpoints were extracted and analyzed descriptively.

Results: The evidence base exhibited a pronounced geographical skew, with 8 of 11 studies originating from Brazil, and no eligible studies from Central America or the insular Caribbean. Synthesis of human studies revealed pervasive subclinical health effects, including respiratory symptoms in ≤ 40% of agricultural workers, endocrine disruption strongly correlated with organochlorine exposure (r = 0.68-0.72; p < 0.001), and cholinesterase inhibition in 63.8% of organophosphate-exposed subjects. Aquatic systems showed widespread contamination, with pesticide and metal concentrations spanning 0.0047 μg/L to 2110 μg/L. Herbicides dominated contaminant profiles, with compounds like clomazone detected in 100% of river samples, while metals including lead demonstrated clear bioaccumulation in fish muscle. Several studies identified latent ecological risks, with arsenic carcinogenicity risk > 10^-6 and herbicide mixtures endangering aquatic biota.

Conclusions: Despite the absence of acute poisoning events, the convergence of evidence signals a latent threat from the pervasive, low-level contamination of LAC's environments. The documented subclinical impairments and clear potential for bioaccumulative escalation underscore an urgent need for enhanced environmental monitoring, stringent regulatory enforcement, and targeted research, particularly in underrepresented regions, to safeguard public health and ecosystem integrity.

[This corrects the article DOI: 10.1155/2024/5261994.].

The Russell's viper (Daboia russelii) has recently become a significant threat to human life in Bangladesh. Given its wide distribution across South Asia, the venom characteristics and lethality can vary by region with different toxicological properties. Hence, we investigated the characteristics of Bangladeshi Russell's viper venom (BRVV) through SDS-PAGE profiling, reverse-phase HPLC analysis, along with assessments of phospholipase A₂ (PLA₂), edema-inducing, hemolytic, hemorrhagic, and coagulant activities, histopathology, and blood biochemistry, following established protocols. We also studied the neutralization efficacy of polyvalent antivenom from VINS Bio Products Ltd., India (VPAV) against BRVV. RP-HPLC analysis of BRVV displayed 15 peaks, and SDS-PAGE showed high-intensity protein bands within the 15-70 kDa range. The median lethal dose (LD₅₀) for mice was found to be 0.33 mg/kg intraperitoneally (i.p.), and venom exposure resulted in neurotoxic symptoms such as limb paralysis, respiratory difficulties, and sluggishness. BRVV exhibited strong PLA₂, procoagulant, hemorrhagic, indirect hemolytic, and edema-inducing activities but poor direct hemolytic activity. Venom administration also significantly increased levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), cholesterol, total protein, uric acid, blood urea nitrogen (BUN), and creatinine in mouse serum, indicating organ damage. Histopathological examination revealed cell vacuolization, congestion, hemorrhage, inflammatory infiltrations, and necrosis in venom-exposed tissues, validating the abnormal serum biochemistry. The neutralization study revealed that VPAV had limited efficacy against BRVV, suggesting the presence of venom proteins not fully neutralized by the antivenom. Altogether, these findings suggest that the Russell's viper is a medically significant venomous snake in Bangladesh, and VPAV is only partially effective in reducing the venom's toxic effects. Therefore, region-specific venoms must be considered in antivenom development for more effective treatment in envenomation cases.

Exposure to zinc oxide nanoparticles (ZnONPs) is more likely due to their wide utilization in the food and pharmaceutical sectors. Therefore, serum neuromarkers and hippocampal tissue were examined for the potential prophylactic impact of folic acid in four groups of rats, each consisting of 10 animals. The first group had 150 mg/kg ZnONPs orally every day for 2 weeks. The second group received 10 mg/kg of folic acid intraperitoneal (ip) for 1 week, followed by ZnONPs daily for 2 weeks. The third group received folic acid only, while the control group was given distilled water. At the end of the experiments, hippocampi were examined, and serum concentrations were measured for glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), monoamine oxidase A (MAOA), and neurofilament light polypeptide (NEFL). ZnONPs-exposed animals exhibited significantly lower levels of GFAP and MBP (p < 0.05 and p < 0.001, respectively) compared to all groups, while the same overdosed animals showed significantly higher levels of MAOA compared to the group that received folic acid prophylaxis (p < 0.001). NEFL levels did not significantly differ among all groups. Histopathological analysis revealed neurodegeneration in the ZnONPs-exposed group, characterized by neuronal shrinkage, hyperchromatic nuclei, vacuolated cytoplasm, and cell loss. Folic acid partially mitigated these effects, preserving Nissl granules and reducing pyknotic changes, though some ghost cells persisted. In summary, the positive impact of folic acid on reducing ZnONPs toxicity is promising to be further investigated as a preventive measure against nanoparticle-induced neurotoxicity.

As part of the valorization of traditional medicine drugs, toxicological studies were carried out on the mixture of the aqueous extract of Persea americana, Cymbopogon citratus, Citrus medica, and honey, a traditional mixture recognized for its antihypertensive activities. The experiments were conducted following modified OECD protocols 425 and 407 for acute and subchronic toxicity tests, respectively. For the acute toxicity, rats were divided into 3 groups of 6 rats (3 females and 3 males). They were given 2 single different doses of aqueous extract of the mixture and distilled water (2000 and 5000 mg/kg, 10 mL/kg). They were observed for the first 24 h and during 14 days. Clinical signs and nature of feces were evaluated. Concerning the subchronic toxicity, six groups of 10 animals each (5 males and 5 females) were used for each dose. The animals of group 1 received distilled water (10 mL/kg), and the animals of groups 2, 3, and 4 received the aqueous extract of the mixture (150, 300, and 600 mg/kg). The animals of groups 5 and 6 were normal satellite control and satellite extract 600 mg/kg. They received, respectively, distilled water (10 mL/kg) and the aqueous extract of the mixture (600 mg/kg). These last two groups were observed 14 days more than the other groups after complete cessation of all treatments. Clinical signs were evaluated and marked by normal fecal matter throughout the experimental period, with a nonsignificant weight variation. After the experiment, rats were sacrificed. For the subchronic toxicity evaluation, blood samples and some organs were taken. Relative organ was calculated, and hematological and biochemical parameters were also evaluated as well as histological sections of organs (pancreas, lungs, liver, kidneys, and spleen). Concerning the acute toxicity, some organs such as the pancreas, lungs, liver, kidneys, and brain were taken and weighed and relative weights were calculated. Administration of the aqueous extract of the mixture daily and for 28 days at the highest dose (600 mg/kg) led to significant increases in the weight of the kidneys (16.25%; p < 0.05) and lungs (58.72%; p < 0.001), and on the other hand, a significant drop in the relative weight of the spleen was observed (49.87%; p < 0.01). A significant increase in the level of leukocytes (p < 0.001) in animals of both sexes treated with the aqueous extract of the mixture at the highest dose was recorded. Treatment of animals with the extract at the highest dose resulted in a significant decrease in triglycerides (p < 0.05) in males. The microarchitecture of histological sections of the organs did not present any notable abnormality apart from a leukocyte shift at 600 mg/kg. The aqueous extract of this mixture is not toxic at the doses used traditionally (50, 100, and 150 mg/kg).

Cameroon rainforest region is not only an agricultural area with massive pesticide uses but also possesses factors that favor land snails' growth like Archachatina marginata. The present study aimed to assess the impact of sub-chronic exposure of commonly used pesticides in Cameroon, glyphosate, metalaxyl, and cypermethrin on the growth, survival, histological structure of key organs, and tissue residue levels in Archachatina marginata. Therefore, sub-adult (under 30 g) Archachatina marginata snails were exposed for 10 weeks, once a week to field-relevant concentrations of glyphosate (0.5 g/L), metalaxyl (3.3 g/L), and cypermethrin (2 g/L), while the control group was exposed with tap water. The experiment was repeated four times. Survival and body weight were recorded weekly. Post exposure, tissue residues were analyzed by GC-MS, and histological examinations of the kidney and ovo-testis (snails' gonad) were performed. The result showed no significant differences in the survival or external morphology of exposed snails. However, deeper statistical analyses revealed that snails exposed to metalaxyl had significantly lower final weights compared to all other groups with a mean loss of -8.7 g (-26.6%). A histological examination revealed visible alteration in the kidney and ovo-testis tissues of treated snails, though these changes could not be confirmed statistically. Moreover, pesticide residues were detected in the tissues of treated animals, with trace amounts of glyphosate and cypermethrin also found in control snails, likely due to prior contamination or cross-cage drift. In conclusion, sub-chronic exposure to field-used pesticides did not induce mortality in Archachatina marginata but did affect growth and tissue integrity, especially under metalaxyl exposure. These findings raise concerns about sub-lethal toxicity and food safety risks and support the use of Archachatina marginata as a bioindicator in pesticide-exposed environments.

[This retracts the article DOI: 10.1155/2016/2973274.].