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

Background

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. Purpose: This study aimed to elucidate the protective impact of SAR against CYC-linked testicular toxicity.

Methods

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.

Results

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.

Conclusions

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.