Background: Cisplatin is one of the most widely used anticancer drugs. As with most of the chemotherapeutic agents, it doesn't only target cancerous cells but is also distributed to normal cells as well causing many organs toxicity. Being the most important organ in the immune system; the spleen affection by cisplatin treatment must be carefully prevented or reversed. This current study aimed to assess the protective effect of a Notch inhibitor dibenzazepine (DBZ) against cisplatin-induced splenic toxicity as well as explore the proposed mechanism shedding light on the role of the Notch pathway in its effect. Methods: Rats were treated with DBZ (2mg/kg) for 12 days with a single dose of cisplatin (7mg/kg) injected on the 8 th day of treatment. Rats were divided into four groups: Control, DBZ, Cisplatin, and DBZ+ Cisplatin group. Results: Cisplatin injection upregulated the oxidative stress markers MDA and iNOS along with reduced antioxidant enzymes glutathione and catalase. The inflammatory markers (TNFα, IL1β, and NK𝜅B) were also upregulated. Furthermore, the Notch-1 and Hes-1 expressions were also significantly elevated. Cisplatin-induced splenic tissue damage was further assured by light and electron microscopic histopathological examination. DBZ pre-treatment significantly restored the upregulated oxidative stress, and inflammatory as well as Notch signaling pathways toward normal levels. Additionally, the histopathological architecture impairment was improved by Dibenzazepine. Conclusions:The study elucidated that DBZ protects against cisplatin-induced toxicity in rats via antioxidative and antiinflammatory effects. Moreover, downregulating the Notch signaling pathway was proved to play a role in DBZ's protective effect against cisplatin-induced splenic toxicity.
Background:The effect of vigorous exercise on testicular function is poorly understood. This work aims to identify the resveratrol influence on the altered reproductive function induced by forced exercise and to screen the relevant possible mechanisms. Methods: The study comprised control, forced exercise (FE), and resveratrol treatment groups carried out on a total of 24 adult male rats. After 8 weeks of the exercise, the pituitary and testicular hormones, corticosterone, tumor necrosis factor (TNF-α), IL-6, epididymal sperm parameters, testicular oxidantantioxidant markers, testicular ornithine decarboxylase (ODC) activity, polyamines, testicular histopathology, and immunohistochemistry for apoptotic reactions were all measured. Results: The FE group showed significant reductions in the pituitary and testicular hormones, sperm count, and motility, while corticosterone, TNFα, IL-6 serum levels, and aberrant forms of sperms were significantly increased. Testicular tissue displayed abnormal architecture, apoptotic changes with a significantly increased malondialdehyde level, ODC activity and polyamines, and a reduction in superoxide dismutase activity. In comparison to the FE group, administration of resveratrol significantly improved the gonadal hormones, corticosterone, TNF-α, IL-6 levels, sperm parameters, oxidant-antioxidant system, ODC activity, and polyamines with an enhancement of testicular architecture and apoptosis. Conclusion: Resveratrol was effective in attenuating testicular dysfunction caused by forced swimming exercise in rats.
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