Saroglitazar Mitigated Cyclophosphamide-Induced Testicular Injury: Crosstalk Between Oxidative Stress, Inflammation and Apoptosis

<b>Background:</b> Cyclophosphamide (CYC) is an effective chemotherapeutic agent and immunosuppressant drug. Former research showed that CYC induces testicular toxicity through oxidative stress, inflammation and apoptosis. Saroglitazar (SAR) is a dual PPARα/γ agonist, used for treatment of diabetic dyslipidemia. <b>Purpose</b>: This study aimed to elucidate the protective impact of SAR against CYC-linked testicular toxicity. <b>Methods</b>: Randomly, thirty adult male rats were alienated into control group, SAR (4 mg/kg) group, CYC (200 mg/kg) group, CYC+SAR (2 mg/kg) group and CYC+SAR (4 mg/kg) group. SAR was orally administered at two doses (2 and 4 mg/kg) for 7 days. CYC was injected intraperitoneally at dose (200 mg/kg) at day 7. <b>Results</b>: In comparison to the CYC group, SAR at the dose of 2 and 4 mg/kg significantly increased testis weight, testicular index, sperm count, serum testosterone and serum luteinizing hormone. Additionally, SAR at both doses induced a significant reduction in testicular MDA content in addition to increased testicular levels of GSH and TAC. Furthermore, SAR markedly upregulated testicular levels of PPARγ, Nrf2 and HO-1 in addition to decreased testicular expression of NF-κB, IL-6 and TNF-α, illustrating its antioxidant and anti-inflammatory effect. SAR also significantly decreased testicular expression of caspase-3 and Bax and increased Bcl2 expression, indicating its anti-apoptotic effect. <b>Conclusions</b>: SAR at doses (2 and 4 mg/kg) could ameliorate CYC-induced testicular injury in rats, possibly through antioxidant, anti-inflammatory and anti-apoptotic effect.