Abstract
Background:
Cisplatin (CSP), a chemotherapy drug widely used for treating solid tumors, can cause cellular toxicity in various percentages. Natural antioxidants, such as phenols, help reduce free radicals and inflammation.

Aim:
This study aimed to investigate the synergistic protective effects of Simmondsia chinensis extract, vitamin E, or their combination, particularly in cases of CSP-induced renal and hepatotoxicity.

Methods:
Fifty adult male rats were randomly grouped into five groups (n = 10): control group (C): each rat received (2 ml/day/orally) distilled water; CSP group: each rat was injected intraperitoneally (IP) with a single dose of (2 mg/ kg) CSP for eight consecutive weeks; and CSP+SCH group: all rats in this group were first injected with cisplatin via IP injection, similar to the CSP group, at the same time administered S. chinensis hydro-ethanolic extract at a dose of (0.6 g/kg/day/orally). In the CSP + Vitamin E group, each rat was treated the same as in the CSP group and then received vitamin E at a dose of 100 mg/kg/day/orally. In the (CSP+SCH+Vit. E) group, rats were IP-injected with cisplatin and then administered both S. chinensis hydro-ethanolic extract and vitamin E, using the same doses as in the third and fourth groups; all treatment administrations were administered over eight consecutive weeks.

Results:
The hepatic enzyme levels of alanine transaminase and aspartate transaminase, as well as malondialdehyde, creatinine, uric acid, cystatin C, and tumor necrosis factor-alpha (TNF-α) were significantly increased in the CSP group compared with all experimental groups. These parameters significantly declined (p < 0.05) in the CSP + SCH + Vit. E group compared with other experimental groups. The injection of cisplatin caused a decrease in the serum concentrations of superoxide dismutase, catalase, and interleukin-10 compared to all treatment groups. All these parameters were significantly elevated (p < 0.05) in the CSP + SCH + Vit. E group and CSP + SCH groups compared with the CSP group. The histological alterations of the renal and hepatic tissues were improved and enhanced in patients with CSP + SCH + Vit. E group compared with all experimental groups.

Conclusion:
Simmondsia chinensis alone or in combination with vitamin E can mitigate cisplatin-induced hepatic and renal toxicity in rats through its synergistic antioxidant and anti-inflammatory properties.

Key words: Cisplatin, Simmondsia chinensis extract, Vitamin E, Nephrotoxicity, Hepatotoxicity.