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The potential testicular protective effect of nimesulide (NSE) was studied in cisplatin (CSP)-challenged rats. NSE therapy (10 mg/kg/day, p.o.) was applied for 15 days, and a single dose of CSP (7 mg/kg, i.p.) was administered on the 10th day. CSP significantly decreased the levels of serum testosterone, testicular reduced glutathione, and superoxide dismutase. CSP also significantly increased testicular malondialdehyde, nitric oxide, tumor necrosis factor-α, interleukin-1β, cyclooxygenase-2 (COX-2), prostaglandin E2, nuclear factor-κB p65, Bax, and caspase-3. NSE significantly ameliorated all the biochemical changes observed in CSP-challenged rats. Moreover, NSE significantly reduced the histopathological injury, and the expressions of phosphorylated c-Jun N-terminal kinase (p-JNK) and p38 mitogen-activated protein kinases (MAPKs) in testes of rats received CSP. It was concluded that NSE significantly blocked the CSP-induced acute testicular injury in rats through inhibition of MAPK/COX-2 signaling pathway, and by combating oxidative stress, inflammation, and apoptosis.
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