Drug and Chemical Toxicology最新文献

Tetradenia riparia (T. riparia) is a medicinal plant native to sub-Saharan Africa, traditionally used but has limited in vivo scientific validation. This study evaluated its antioxidant, toxicity, and anti-inflammatory effects using in vivo toxicity tests, paw edema, air pouch models, and vascular permeability assessment. Additionally, qualitative phytochemical analysis and quantitative measurements of total polyphenolic and flavonoid content were conducted. In vitro assays revealed significant concentrations of polyphenolic and flavonoid compounds, demonstrating notable radical scavenging activities in DPPH, phosphomolybdate, and FRAP assays. In vivo studies demonstrated that T. riparia extract showed no indications of acute or sub-acute oral toxicity, even when administered at the highest tested dosage of 5000 mg/kg body weight (LD50 > 5000 mg/kg). Toxicity assessments confirmed its safety, showing no fatalities, significant organ damage as evidenced by histopathological analysis, or substantial adverse effects on most hematological and biochemical parameters. The hydroalcoholic extract of T. riparia demonstrated a notable anti-inflammatory effect that increased with dosage. The inhibition percentage of paw edema by the extract was high at 3 hours, reaching 39.13 ± 8.78%. Nitric oxide (NO) inhibition at doses of 0.5 g/kg and 1 g/kg was recorded as 36.09 ± 2.13% and 49.96 ± 5.41%, respectively. Regarding vascular permeability, T. riparia extract significantly reduced dye leakage (p < 0.05 and p < 0.001), with inhibition percentages of 61.57% and 75.25% at doses of 0.5 g/kg and 1 g/kg, respectively. These findings highlight its promising potential as a treatment for inflammatory disorders. In conclusion, phytochemical analysis identified compounds, which are believed to be responsible for the pharmacological effects observed. Further studies are needed to investigate the chronic consumption of hydroalcoholic extract for long-term isolate bioactive compounds, understand their mechanisms, ensure comprehensive safety profiles for potential drug development, and elucidate their anti-inflammatory mechanism.

This study investigates the effects of Bacillus coagulans ATCC7050 probiotic supplementation on the growth performance, immune function, antioxidant activity, and liver health of rainbow trout (Oncorhynchus mykiss) exposed to the herbicide pretilachlor. Over 30 days, the fish were fed diets supplemented with B. coagulans (1 × 10⁶ or 1 × 10⁸ CFU/g) and/or 12.5% pretilachlor. Probiotic supplementation significantly enhanced growth parameters and reduced the feed conversion ratio, whereas herbicide exposure had the opposite effect (p = 0.000). Immune responses, including lysozyme activity and total immunoglobulin levels, were improved by probiotic treatment but suppressed by pretilachlor exposure (p = 0.001). Additionally, the probiotic increased antioxidant enzyme activity and reduced markers of oxidative stress. Liver function indicators elevated due to herbicide exposure were mitigated by B. coagulans supplementation (p = 0.028). These findings underscore the potential of B. coagulans to counteract herbicide-induced toxicity, supporting fish health and promoting more sustainable aquaculture practices.

Sansevieria trifasciata (S. trifasciata) has been widely recognized in traditional medicinal systems for its therapeutic potential from the Bundelkhand region of India. The current study investigates the potential efficacy of S. trifasciata against Dynapar (diclofenac)-induced toxicity. We conducted phytochemicals screening and gas chromatography-mass spectrometry (GC-MS) analysis of S. trifasciata leaf aqueous extract (STLAE), revealing diverse bioactive compounds, including saponins, phenols, tannins, glycosides, carbohydrates, and terpenoids. GC-MS analysis further identified 10 specific compounds, notably nitrogen-containing heterocycles, esters, amides, and methoxyacetic acid derivatives, providing molecular insights into the plant's traditional medicinal applications. Using zebrafish (Danio rerio) as an ethically sound vertebrate model, we established Dynapar's 96-hour median lethal concentration (LC₅₀) at 1.5 mL/L (112.5 mg/L). Co-administration experiments demonstrated that STLAE at 2.2 mL/L (220 mg/L) completely prevented Dynapar-induced mortality, suggesting a defined therapeutic window for protective effects. Interestingly, STLAE showed a dose-dependent response curve, with lower and higher concentrations exhibiting reduced protection, highlighting the importance of precise dosing in natural product applications. Our findings provide the first experimental evidence supporting S. trifasciata's traditional use in treating inflammatory conditions and suggest its potential as a natural intervention against NSAID-induced toxicity. The identified nitrogen-containing compounds and other phytoconstituents likely contribute to the observed protective effects by modulating oxidative stress pathways implicated in Dynapar toxicity. This work establishes groundwork for further investigation into S. trifasciata as a safer alternative for managing chronic inflammatory conditions.

The current study was designed to determine potential therapeutic role of R. hastatus leaf extract against Triclosan (TCS)-induced testicular toxicity. The methanolic extract of R. hastatus was evaluated for its antioxidant potential, while GC-MS analysis was carried out to identify bioactive components in the extract. For the toxicity study, forty adult male rats were divided into four groups. One group was set as control group whereas, other three groups were given TCS (50 mg/kg), R. hastatus extract (RE, 150 mg/kg) and TCS+RE (50 mg/kg + 150mg/kg) orally for 30 consecutive days. Results showed that TCS exposure caused significant alteration in sperm parameters, and reduced antioxidant enzyme activity while increasing the concentration of oxidative stress markers. Moreover, DNA integrity was compromised along with testicular histopathological damage and lowered levels of reproductive hormones. Fertility test revealed reduced pregnancy outcomes and small litter sizes in females paired with TCS-treated males. RE treatment effectively normalized the attributes of sperm parameters and enzymatic activities of antioxidants. Additionally, co-treatment of RE restored the hormonal levels thus normalizing testicular architecture. Increased pregnancy outcomes and litter size in RE-treated animals were also recorded. So, it is concluded that R. hastatus plant extract has the potential to attenuate TCS-induced reproductive toxicity using antioxidant potential.

Arsenic contamination of ground water is a global problem. Consumption of smokeless tobacco called 'sadagura' is a common lifestyle practice in Assam, India. As a result, the population is more vulnerable to health outcomes with regard to female reproductive anomalies. Phytochemicals are abundant in antioxidants, the current study examined the protective effects of quercetin (Qc) and curcumin (Cur) against the toxicity caused by smokeless tobacco and arsenic. Female Swiss albino mice (N = 66) were randomly divided into eleven different groups viz., Control, Positive control (DMSO), Sodium arsenite (SA), Sadagura(SG), SA+SG, SA+Qc, SG+Qc, SA+SG+Qc, SA+Cur, SG+Cur, and SA+SG+Cur. Estrous cycle; ovarian and uterine histopathological changes were recorded. Utilizing the comet assay, the DNA damage of tissues was examined, and biochemical analysis was performed to determine oxidative stress level. The study of estrous cycle showed that changes in different phases of estrous cycle was altered by both As and SG exposure. However, Qc and Cur exposure showed a significant notable recovery. It was observed that Qc and Cur lowered the DNA damage induced by As and SG. Histological examinations showed abnormal tissue architecture in mice treated with SG and SA that is restored by administration of curcumin and quercetin. In contrast to As and SG treatment, quercetin and curcumin supplementation significantly increased GSH and SOD activity in experimental mice. According to the current study, curcumin and quercetin lowered the induced oxidative stress. Therefore, these phytochemicals can act as a protective mediator against the female reproductive toxicity caused by smokeless tobacco and arsenic coexposure.

New psychoactive substances (NPS) are a broad category of drugs that pose public health risks and have poorly characterized pharmacological properties. Further studies are critical for risk assessment, toxicological profiling, and intoxication management. Human evaluations are limited by ethical and safety constraints, making animal models essential. Among in vivo models, zebrafish (Danio rerio) deserves emphasis in the study of NPS due to neurobehavioral, metabolic, and toxicological alterations. Considering some advantages, such as high genetic and neurochemical homology to humans, small body size, external fertilization, and embryo-larval transparency, zebrafish is well-suited for high-throughput screening of NPS. Their central nervous system shares key neurotransmitter pathways with mammals, supporting neurobehavioral assays. Also, a conserved cytochrome P450 system allows metabolism studies. Zebrafish have been successfully used to investigate NPS effects, with embryo-larval models offering practical advantages for acute toxicity and high-throughput behavioral screening. Adults, in turn, are more appropriate for complex behaviors and long-term or chronic exposure protocols. This review synthesizes for the first time behavior, toxicology, and metabolism data from zebrafish studies with a range of NPS classes within a unifying framework, to deliver a comprehensive understanding of their in vivo activity. By focusing on the translational value of zebrafish research, this review bridges experimental toxicology and clinical and forensic applications, thus filling a significant gap in current knowledge and demonstrating how zebrafish models can uniquely accelerate NPS toxicity profiling by providing mechanistic and behavioral information with high translational value.

The aim of this study was to determine the antidotal potential of the chlorinated oxime K870 compared to obidoxime, as a monotherapy and in combination with atropine, in paraoxon (POX)-poisoned rats. The treatment doses of oximes were chosen as 20% of their LD₅₀ values. The protective ratio (PR) of oxime K870 with atropine was significantly higher than that of obidoxime with atropine (68.8 and 125.0, respectively). In the biochemical part of the experiment POX subcutaneously (s.c.) (0.75% LD₅₀) was administered and followed by oxime K870 or obidoxime i.m. 1 min later. Acetylcholinesterase (AChE) activity was determined spectrophotometrically in cerebrum, cerebellum, brainstem, diaphragm, and erythrocytes. Carboxylesterase activity was determined in plasma and liver. Both oximes successfully reactivated AChE in brain (cerebrum, cerebellum, and brainstem), diaphragm and erythrocytes, but the oxime K870 performed better than obidoxime. Both oximes reactivated carboxylesterase, obidoxime better in plasma and oxime K870 better in liver. In conclusion, the oxime K870, when co-administered with atropine, is a more effective antidote than the obidoxime-atropine combination in POX-poisoned rats.

In this study, the protective effect of astaxanthin (AST) against cyclophosphamide (CP) induced adult rat heart damage was investigated. Eighteen rats were divided into 3 groups as Group 1: control, Group 2: cyclophosphamide and Group 3: cyclophosphamide + astaxanthin. The CP group, received a 200 mg/kg single dose intraperitoneal (i.p.) injection of CP on the seventh day of the experiment, while the control group received no treatment. For CP+AST group 25 mg/kg/day AST administered by oral gavage on days 1-7 and on the 7th day 200 mg/kg/day CP was administered by i.p injection. On the 8th day, the rats were sacrificed by exsanguination and the hearts were dissected. Histopathological examinations were performed by Hematoxylin&Eosin (H&E), Masson Trichrome and Periodic Acid-Schiff (PAS) staining methods; Annexin-V and Anti-NOX2/gp91phox analyzes were performed by flow cytometry. In histological evaluation of the CP Group; disruptions in cardiac histology and increased PAS(+) staining were observed. These findings were reduced in the CP+AST group compared to the CP group. According to flow cytometry measurements, there was an increase in Annexin-V and Anti-NOX2/gp91phox bound cells in the CP group. With the AST pretreatment, in the CP+AST group Annexin-V and Anti-NOX2/gp91phox bound cell level showed decrease. Based on our study's data, CP may alter cardiac histology and have a negative impact on apoptosis and oxidative damage processes. Astaxanthin may ameliorate these effects of CP on the heart. To enhance the assessment of this protective effect, we propose conducting future research utilizing varied dosages, application durations and advanced analytical techniques.

This study aims to elucidate the potential roles of commonly used plasticizers, including Diethyl Phthalate (DEP), Dimethyl Phthalate (DMP), and Dioctyl Phthalate (DOP), in the pathogenesis of Acute Myeloid Leukemia (AML). The focus is to highlight the complex interactions between these environmental chemicals and key molecular pathways involved in tumorigenesis. We employed network toxicology and molecular docking techniques to analyze the interactions between plasticizers and key proteins associated with AML. Utilizing databases such as The Cancer Genome Atlas (TCGA), we divided selected key genes from AML bone marrow samples into two groups based on gene expression and compared their survival analyses. Enrichment analysis was conducted to identify the biological pathways associated with these genes. The enrichment analysis underscored the association between the plasticizer-targeted genes and essential pathways in AML development, indicating a broad impact of plasticizers on various cancers, including hematologic malignancies. Subsequent expression analysis using TCGA data for AML demonstrated that these genes have significant statistical relevance to the survival in AML, confirming their critical roles in tumor biology. This study provides evidence that exposure to plasticizers could influence the pathogenesis of AML through interactions with key proteins and signaling pathways. By utilizing network pharmacology and protein interaction analysis, our findings emphasize the potential risks associated with plasticizers. These results highlight the necessity for further epidemiological and clinical research to fully understand the impact of plasticizer exposure on AML risk, thereby informing future preventive and therapeutic strategies.

Silymarin is an extract of Silybum marianum that is used traditionally for the treatment of several diseases. This study sought to evaluate the protective effects of silymarin on cobalt chloride (CoCl₂)-induced cardio-renal toxicities in rats. Forty rats were randomly divided into four groups of 10 rats each: control; 300 mg/kg CoCl₂; CoCl₂ + 100 mg/kg silymarin; and 100 mg/kg silymarin only. All administrations were done orally. At the end of the experimental period (seven days), blood pressure parameters, markers of oxidative stress, antioxidant defense status, renal function test, histopathology and immunohistochemical expressions were evaluated on the heart and kidney tissues. Silymarin significantly (p < 0.05) altered CoCl₂-induced alterations in blood pressure parameters, antioxidants and markers of oxidative stress, blood urea nitrogen and creatinine. Histopathological evaluation revealed area of infiltration of the myocardium by inflammatory cells and hemorrhages in the kidney of rats exposed to CoCl₂ without silymarin treatment, but these lesions were absent in the control and silymarin groups. Increased immunohistochemical expression of cardiac troponin I and matrix metalloproteinase-2 (MMP-2) was observed in the cardiac tissues of rats exposed to CoCl₂ without silymarin treatment. The immunohistochemical expression of cystatin C was heightened, while that of angiotensin-converting enzyme 2 (ACE2) was attenuated in the CoCl₂ untreated group compared with the control and silymarin groups. In conclusion, silymarin effectively mitigated the toxic effects of CoCl₂ on the heart and kidney tissues of rats due to its ability to positively modulate the activities of endogenous antioxidants and neutralize reactive oxygen species in cardiac and renal systems.