The integrated effect of roflumilast and selenium nanoparticles on nephrotoxicity generated by cisplatin through the regulation of the antioxidant and apoptotic pathways.

AIM

The current investigations aimed to investigate the potential synergistic effect of Roflumilast (ROF) and Selenium nanoparticles (SeNPs) administration on Cisplatin (Cis) -induced nephrotoxicity.

MATERIALS AND METHODS

Fifty male rats were divided into five groups; Control group: animals were administered 0.9 % saline solution. Cis group: animals were injected with a single dose of 6 mg/kg. ROF group: Rats received a dosage of 1.2 mg/kg orally daily for 11 days. SeNPs group: animals orally received 0.5 mg/kg of ROF daily for 11 days. The ROF + SeNPs group was administered both after receiving a Cis injection for 11 days. Animals were sacrificed at 5 and 11 days, and the urine and blood samples were collected on day 5 and day 11 for chemical analysis, while kidney samples were obtained for molecular, histological, and immunohistochemical studies.

RESULTS

The levels of serum creatinine, Blood urea nitrogen (BUN), and total protein were elevated in the Cis group compared to the control group (p < 0.05). While the combination of ROF and SeNPs dramatically decreased these values after 5 and 11 days (p < 0.05). In addition, Cis caused renal oxidative stress by elevating MDA levels and suppressing the activities of SOD, GSH, and CAT. Similarly, these effects were modulated by ROF and SeNPs after 11 days (p < 0.05). Furthermore, the concurrent administration of ROF and SeNPs resulted in a significant increase in the expression of HO-1, Nrf2, and Bcl2, while decreasing the expression of BAX and IL-6 compared to the Cis group after 11 days (P < 0.05).

CONCLUSION

The study showed that both ROF and SeNPs had significant therapeutic potential in reducing the pathological alterations caused by Cis.