Human & experimental toxicology最新文献

BackgroundDexmedetomidine (DEX) can offer protection to the nervous, urinary and circulatory systems. It can alleviate local oxidative stress, reduce inflammatory responses, inhibite cellular autophagy and decrease apoptosis.AimTo explore the potential protection and possible mechanisms of DEX against propofol (PPF)-induced memory impairment in developing rats.Material and methodsThe effects of DEX on spatial learning and passive avoidance abilities of rats were evaluated using eight-arm mirror maze and passive avoidance experiments. mRNA levels were detected using RT-qPCR analysis while protein levels were determined using western blot. A network pharmacology approach was used to predict potential targets of DEX against PPF-induced memory impairment. The cell autophagy and apoptosis were detected using commercial kits.ResultsDEX improved the impairment of developing rats on spatial learning and passive avoidance caused by PPF exposure. DEX regulates autophagic activity to inhibit neuronal apoptosis. RARα and Src were potential targets for DEX against memory impairment caused by PPF exposure. DEX upregulated the expression levels of Bdnf, p-CREB/CREB, p-Akt/Akt, and p-TrkB/TrkB proteins.ConclusionDEX may regulate Bdnf/TrkB and activate the activity of the PI3K/Akt signaling pathway by targeting RARα and Src, thereby inhibiting excessive autophagy and alleviating memory impairment.

IntroductionFor many years, 5-fluorouracil (5-FU) has been utilized as a chemotherapeutic treatment for a variety of malignancies. Unfortunately, 5-FU causes cardiotoxicity, which restricts its clinical use. Nifuroxazide (NFX) is a STAT-3 inhibitor with antioxidant and anti-inflammatory effects.MethodsCardiotoxicity was induced by 5-FU (30 mg/kg) once daily for 5 days. NFX was administered in two doses, 25 and 50 mg.ResultsCompared to 5-FU-control rats, NFX significantly attenuates cardiotoxicity induced by 5-FU, as indicated by decreasing creatine kinase (CK)-MB, aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) serum levels. Histopathological examinations confirmed the protective effects of NFX against histological abrasions induced by 5-FU. NFX attenuated the oxidative damage induced by 5-FU mediated by peroxisome proliferator-activated receptor gamma (PPAR-γ) signal activation. Moreover, NFX mitigated 5-FU-induced inflammation by suppressing nucleotide-binding domain, leucine-rich repeat-containing protein 3/signal transducer and activator of transcription 3 (NLRP3/STAT3) signal activation. Notably, these protective effects are dose-dependent. Additionally, NFX mitigated 5-FU-induced apoptosis by downregulating Bax, while upregulating Bcl-2.ConclusionsCollectively, NFX attenuated 5-FU-induced cardiac intoxication by regulating NLRP3/STAT-3, PPAR-γ, and Bax/Bcl-2 signals.

BackgroundCyclophosphamide (Cyp) is associated with various organ toxicities. The study aimed to investigate the efficacy of zofenopril (Zf), thymoquinone (Thym), and their combination in Cyp-induced cardiotoxicity.MethodologyThirty rats were divided into five groups of six rats each. They received the following treatment orally for 19 days: Control (Con) and Cyp groups: normal saline. Zf: Zf 15 mg/kg, Thym: Thym 80 mg/kg, and Zf + Thym: a combination of both. A single dose of Cyp 200 mg/kg intraperitoneally (IP) was given on day 17 of the experiment to all the groups except the Con. Cardiac, inflammatory, and apoptotic biomarkers, including troponin T, lactate dehydrogenase (LDH), CK-MB, hs-CRP, nuclear factor kappa B (NF-κB), caspase-3, and total antioxidant capacity (TAC), along with lipid profile and histopathological lesions, were assessed.ResultsCyp resulted in cardiotoxicity as manifested by a significant increase in troponin T, CK-MB, caspase-3, hs-CRP, suppression of TAC level, and marked histopathological alterations in cardiac tissues. Zf, Thym, and their combination significantly reduced CK-MB levels. NF-κB level was significantly decreased by Thym, while the combination of Zf and Thym significantly elevated TAC. hs-CRP was significantly reduced only by Zf. Caspase-3 were significantly lowered by both Zf and Thym individually, as well as by their combination.ConclusionZf and Thym provided cardioprotection against Cyp-induced cardiotoxicity through distinct mechanisms. Zf exhibited anti-inflammatory effects, evidenced by a significant reduction in hs-CRP, along with anti-apoptotic activity. Thym significantly suppressed NF-κB expression. Their combination enhanced antioxidant capacity, however, no superiority over individual treatments was observed concerning their other actions.

IntroductionDoxorubicin (DXR), a chemotherapeutic antibiotic, is widely used as an anticancer drug in clinics. Grape seed extract is known for its potent antioxidant properties. The aim of this study is to investigate the effect of high-antioxidant content Vitis vinifera L. seed extract against DXR-induced testicular and epididymal damage.Methods30 male rats were randomly divided into five groups with six animals in each group: Control, Sham, DXR (a single i.p. dose of 15 mg/kg), DXR + VIT (120 mg/kg VIT seed extract via gavage for 14 days and a single i.p. dose of DXR (15 mg/kg) on day 5, VIT (120 mg/kg VIT seed extract via gavage for 14 days). Animals were sacrificed under anesthesia 24 hours after the last drug administration, and blood, testis, and epididymis tissues were collected.ResultsTissues from the DXR group exhibited atrophic seminiferous tubules, Leydig cell degeneration, tunica albuginea and basal membrane thinning, immature spermatogenic cells, vascular congestion, epididymal atrophy, epithelial cell deletion, decreased sperm count, increased connective tissue, and absence of sperm in the lumen. Serum levels of interleukin 6 (IL-6), interleukin 1β (IL-1β), Tumor Necrosis Factor α (TNF-α), Total Oxidant Status (TOS), Total Antioxidant Status (TAS), and testosterone were increased in the DXR group, while interleukin 10 (IL-10) levels were decreased. The DXR + VIT group showed a near-recovery similar to the control.ConclusionDXR increased oxidative stress, apoptosis, and inflammation in the testis and epididymis, whereas VIT exhibited protective effects against these damages.

BackgroundGlufosinate ammonium (GLA) is a widely used herbicide in rural Vietnam, often associated with severe toxicity. Given the limited diagnostic resources at primary care levels, identifying simple and effective predictors of severity is critical for early triage and intervention.ObjectiveTo identify clinical and biochemical predictors of severe outcomes in patients with glufosinate ammonium poisoning using multivariable logistic regression.MethodsWe conducted a retrospective study of 83 patients with confirmed glufosinate ammonium poisoning admitted to our poison control center at Bach Mai hospital between March 2023 and October 2024. Demographic, clinical, and laboratory data were collected. Severe outcomes were defined as the need for mechanical ventilation, inotropic support, Glasgow Coma Score ≤8, or in-hospital mortality. Logistic regression was used to identify significant predictors and evaluate model performance.ResultsThe mean age was 48.6 ± 17.3 years; 62.7% were male; 88% of cases resulted from intentional ingestion; six patients died (7.2% mortality). Significant predictors of severe outcomes included glufosinate ammonium ingestion >100 ml, (Odds Ratio (OR) 4.5, p < 0.001), time to hospital >6 h (OR 3.2, p = 0.004), pH < 7.35 (OR 5.7, p < 0.001), lactate >4.0 mmol/L (OR 6.2, p < 0.001), creatinine >110 µmol/L (OR 4.3, p = 0.005), and NH₃(ammonia) > 100 µmol/L (OR 5.4, p = 0.002). The final logistic regression model including pH < 7.35, time to hospital >6 h, NH₃ > 100 µmol/L, and ingested volume >100 mL demonstrated good discrimination (AUC = 0.84, 95% CI 0.74-0.93; p < 0.001) and acceptable calibration by the Hosmer-Lemeshow test (p = 0.47).ConclusionReadily available clinical and laboratory indicators, such as pH < 7.35, delayed hospital arrival, high ammonia levels, and large ingested volume, were strong predictors of severe outcomes in glufosinate ammonium poisoning. The simple logistic model (AUC = 0.84) may support early triage in low-resource settings, but prospective validation is needed.

Background: Until now, no definite standardized method has been used to promptly assess the severity and outcome of acute aluminum phosphide (ALP) poisoning. The current study aimed to evaluate the performance of the new Poisoning Mortality Score (PMS) and PGI score for predicting mortality in acute ALP-poisoned patients, highlighting the accuracy of new PMS components.

Patients and methods: A 2-year cross-sectional study was conducted on ALP-poisoned patients admitted to Tanta University Poison Control Centre from April 2021 to March 2023. Socio-demographics, poisoning data, and initial vital signs were recorded. Additionally, new PMS and PGI scores were calculated on admission. Patients were categorized according to the mortality outcome into survivors and nonsurvivors.

Results: Out of 160 included ALP poisoned patients, mortality was recorded in 112 (70%) patients. The nonsurvivors had significantly higher median PGI and new PMS values than survivors. New PMS, vital signs component of new PMS, and PGI conveyed good discriminatory power for predicting mortality (AUC = 0.883, 0.873, and 0.817, respectively). Although the new PMS outperformed PGI in all predictive metrics, no significant difference in AUCs was observed between the new PMS and its vital signs component.

Conclusion: The new PMS vital signs component is closely aligned with the new PMS. Thus, it can be used as a valid, comprehensive, and practical tool to substitute the whole score calculation for rapid ALP-poisoned patient assessment to enhance emergency clinical decision-making.

Introduction: The outbreak of acute kidney injury (AKI) due to mushroom poisoning is not a frequently encountered medical challenge. Herein, we present 13 mushroom poisoning cases associated with AKI related to Amanita Proxima (A. Proxima) causing poisoning reported in a short time period in Turkey.

Methods: A total of 13 patients with AKI due to mushroom poisoning admitted to Usak Research and Training Hospital between November and December 2020 were included. Under morphological and microscopical investigations of mushroom specimens (from three patients), the species of the mushrooms were identified.

Results: The median age of 13 patients presenting with AKI due to mushroom poisoning was 55 (ranging between 19 and 72 years), and 60.4% were males. Nausea and vomiting were the first symptoms in most patients and appeared at a mean time of 12.8 ± 7.6 h after ingesting mushrooms. Mean serum creatinine on admission was 7.2 ± 3.8 mg/dL. Kidney replacement therapy (KRT) was administered to all patients, and mortality occurred in two due to sepsis and heart failure (HF). Species of the mushroom specimens obtained from three patients were identified as A. Proxima, a rarely encountered type of mushroom. A. Proxima has a considerable similarity to a common and edible species specific to the Mediterranean Basin, known as A. Ovoidea.

Discussion: Based on our findings, we emphasize the consideration of nephrotoxic mushrooms of the genus Amanita in the evaluation of mushroom poisoning cases, as well as the efforts needed to increase public awareness regarding the risk of fatal outcomes of consuming wild mushrooms.

Introduction: Organophosphate pesticides (Ops) like diazinon (DZN) have well-known neurotoxic effects and low-level chronic exposure has been linked to detrimental neurobehavioral impairments and memory deficits. However, it's not entirely clear how DZN-induced biological changes, particularly in the prefrontal cortex (PFC) contribute to these effects. The purpose of this study is to investigate the impact of DZN exposure on inhibitory avoidance (IA) memory function, amyloid precursor expression (APP), and proinflammatory tumor necrosis factor-α (TNF-α) levels in the rat cortex.

Materials and methods: Rats were divided into 4 groups and recived 2 mg/kg DZN for 5-days or 12-weeks and two control groups recived the same volume of vehicle. IA memory was assesed using the shuttle box apparatus. Rats were sacrificed and the prefrontal cortex PFC were removed. Real-time PCR and Western blotting were used to messure TNF-α, and amyloid protein precursors gene expression and protein levels.

Results: Our findings indicated that DZN caused body weight loss and a notable decline in performance on the IA memory. Additionally, 5-days exposure increased APP and APLP2 protein levels in the PFC, while 12-weeks exposure decreased these levels. Furthermore, expression of APP and APLP2 gens were decreased in PFC. TNF-α levels increased as a result of 5-days exposure to DZN, but these levels dropped to normal after 12-weeks administration, and this observation was significant.

Conclusion: Taken together, exposure to low doses of DZN leads to disturbances in IA memory performance and also alternations in amyloid beta precursors that can be related to increased risk of Alzheimer's disease.