Clozapine (CLZ) is considered the most effective drug in treatment of resistant schizophrenia. However, its cardiotoxic effect has raised concerns about its safety. Captopril is a well-known angiotensin-converting enzyme inhibitor with unique antioxidant properties. The aim of this study was to investigate the protective effect of captopril against CLZ-induced myocarditis, and since both drugs have hematotoxic effects, this study aimed to clarify the effect of their combined use on the bone marrow. The study was conducted for 4 weeks on 50 adult male albino rats divided into five groups: group I (negative control), group II (positive control), group III treated with captopril 5 mg/kg/day, group IV treated with CLZ 25 mg/kg/day, and group V treated with captopril (5 mg/kg) 1 hour before CLZ (25 mg/kg/day). CLZ group showed a significant increase in serum troponin I, marked histopathological changes, and immunohistochemical staining of DNA degradation product 8-hydroxy-2-deoxy guanosine (8-OHdG). It significantly increased malondialdehyde level and decreased glutathione peroxidase. Captopril coadministration decreased the histopathological hallmarks and biochemical marker of myocarditis and attenuated CLZ effects on the oxidative stress parameters and 8-OHdG, suggesting its protective action against CLZ-induced myocarditis. Complete blood count and bone marrow evaluation was normal indicating that captopril, in the protective dose given, didn't increase the risk of CLZ-induced hematotoxicity

Background: Toluene is a volatile organic compound that is commonly used in a variety of applications around the world, including paints, inks, solvents, varnishes, plastics, thinners, fabrics, and dyes. This enhances the probability of exposure in occupational and environmental settings. Aim of the work: This research was carried out in adult male albino rats to look into the hepatic and renal histopathological changes caused by acute toluene exposure, the possible underlying mechanisms, and the role of buffalo milk in reducing the toxic effects of toluene. Methodology: The study was conducted for 7 days on seventy-two adult male albino rats. They were divided into five groups as follow: Group I (negative control): 12 rats were fed with regular diet and water to test basic parameters .Group II (positive control) 24 rats subdivided into 2 equal groups: Subgroup IIa (corn oil group)12 rats received 1 ml of corn oil (vehicle of toluene) by oral gavage . Subgroup IIb (distilled water group) 12 rats received 1ml of distilled water by oral gavage. Group III (pasturalized buffalo milk group -PBM) 12 rats received 1ml of buffalo milk by oral gavage. Group IV (toluene group) 12 rats received toluene 900mg/kg dissolved in corn oil by oral gavage. Group V (toluene and pasturalized buffalo milk group) 12 rats received toluene 900mg/kg followed by 1ml of buffalo milk by oral gavage for 7 days. At the end of the study, blood samples were collected for estimating (serum ALP, ALT, serum albumin, serum creatinine, serum MDA, TAC). Then livers and kidneys were extracted for histopathological (H&E) and immunohistochemistry (caspase-3) examination. Results: The result of the study revealed that administration of toluene for 7 days induced significant increase in ALP, ALT, creatinine, serum MDA and significant reduction in serum albumin and TAC. It also induced histopathological alterations in liver and kidney with increased caspase-3 immunoreactivity. Administration of PBM with toluene for 7 days improved toluene induced histopathological alterations in liver and kidney with decreased caspase-3 immunoreactivity. Also, PBM caused significantly beneficial effect on liver and kidney parameters; In addition, it decreased serum MDA level and increased serum TAC. Conclusion: Buffalo milk has partial protective effects against toluene induced hepatotoxicity, nephrotoxicity, oxidative stress and apoptosis.