Modulatory effects of perindopril on cisplatin-induced nephrotoxicity in mice: Implication of inflammatory cytokines and caspase-3 mediated apoptosis

Cisplatin-induced nephrotoxicity limits its anticancer effectiveness, thus this study’s aim was to assess the potential modulatory effect of perindopril on cisplatin-induced nephrotoxicity and to elucidate the possible underlying mechanisms. Renal dysfunction was induced in mice by a single injection of cisplatin (10 mg kg–1, i.p.) and perindopril was administered orally (2 mg kg–1, once daily) for 5 days. Perindopril remarkably ameliorated cisplatin-induced perturbations in renal histology, renal levels of tumor necrosis factor-alpha, interleukin-6 and interleukin-10, apoptosis-regulating protein expressions (Bax and Bcl2), and partially normalized Bax to Bcl2 ratio and active caspase 3 protein expression. Conversely, perindopril had no significant effect on cisplatin-induced elevations in serum creatinine and urea, microalbuminuria, kidney to body weight ratio, lipid peroxidation marker, superoxide dismutase and catalase activities and reduced glutathione content. In conclusion, perindopril may be safely used with cisplatin in mice since it ameliorated cisplatin-induced histopathological changes, inflammation and apoptosis without affecting renal biomarkers or oxidative stress

Crocin mitigates carbon tetrachloride-induced liver toxicity in rats

AbstractObjectivesCarbon tetrachloride (CCl4) is one of the most dangerous hepatotoxic environmental pollutants thus this study aimed at investigating the potential preventive effect and mechanism of crocin against CCl4-induced hepatotoxicity.MethodsForty Male rats were allocated for two weeks treatment with; corn oil, CCl4 in corn oil, crocin (100mg/kg), or crocin plus CCl4. At time of euthanasia liver was removed, weighted and processed for histopathological evaluation and estimation of liver contents of active caspase3, lipid peroxidation (MDA) and reduced glutathione (GSH). We also evaluated antioxidant enzymes activities [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)], phase I metabolizing enzyme [cytochrome P450 sub family 2E1 (CYP2E1)] an Phase II metabolizing enzyme, [glutathione-S-transferase (GST)] in liver tissue. Blood samples were used for evaluation of liver function tests and inflammatory cytokines [interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α)].ResultsCCl4 induced significant (p < 0.001), increase in: relative liver weight to body weight, liver MDA content, liver active caspase-3 and plasma levels of IL-6 and TNF-α. In addition, CCl4 disturbed liver histology, liver metabolizing enzymes (CYP2E1 and GST), and liver function tests (aspartate aminotransferase, alanine aminotransferase, total bilirubin and alkaline phosphatase). CCl4 induced significant decrease in activities of SOD, CAT, GSH-Px and GSH content. Administration of crocin with CCl4 mitigated all CCl4-disturbed parameters and preserved liver histology close to normal.ConclusionCrocin ameliorated CCl4-induced liver injury via inhibition of inflammatory cytokines, caspase3 and oxidative stress along with modulation of liver metabolizing enzymes favoring elimination of CCl4 toxic metabolite

Modulatory effects of perindopril on cisplatin-induced nephrotoxicity in mice: Implication of inflammatory cytokines and caspase-3 mediated apoptosis

Cisplatin-induced nephrotoxicity limits its anticancer effectiveness, thus this study’s aim was to assess the potential modulatory effect of perindopril on cisplatin-induced nephrotoxicity and to elucidate the possible underlying mechanisms. Renal dysfunction was induced in mice by a single injection of cisplatin (10 mg kg−1, i.p.) and perindopril was administered orally (2 mg kg−1, once daily) for 5 days. Perindopril remarkably ameliorated cisplatin-induced perturbations in renal histology, renal levels of tumor necrosis factor-alpha, interleukin-6 and interleukin-10, apoptosis-regulating protein expressions (Bax and Bcl2), and partially normalized Bax to Bcl2 ratio and active caspase 3 protein expression. Conversely, perindopril had no significant effect on cisplatin-induced elevations in serum creatinine and urea, microalbuminuria, kidney to body weight ratio, lipid peroxidation marker, superoxide dismutase and catalase activities and reduced glutathione content. In conclusion, perindopril may be safely used with cisplatin in mice since it ameliorated cisplatin-induced histopathological changes, inflammation and apoptosis without affecting renal biomarkers or oxidative stress

Synthesis and evaluation of some new 1,2,4-triazolo(4,3-a)quinoxalin-4-5H-one derivatives as AMPA receptor antagonists

This study involves the synthesis and anticonvulsant evaluation of 1-ethyl-3-hydrazinylquinoxalin-2-1H-one (8), and many other newly synthesized compounds (9–14). The structure of the synthesized compounds was confirmed by elemental analysis and spectral data (IR, 1H NMR and Mass). Docking studies were performed to all the synthesized compounds in order to rationalize the anticonvulsant activity of the proposed compounds in a qualitative way. There is a strong correlation between the results of molecular modeling and the anticonvulsant activity of the synthesized compounds. The highest fitting value was noticed for compounds 9 and 10 “which showed the highest anticonvulsant activity”