Spinosin Alleviates Cyclophosphamide-Induced Oxidative Stress, Inflammation, and Apoptosis in Liver and Kidney Injury...

In the present study, we investigated the protective effects of spinosin (SP) against cyclophosphamide (CYC)-induced hepatorenal toxicity in a mouse model. Fifty-six animals were randomly divided into eight groups. The control group received an intraperitoneal (i.p.) injection of 0.1 mL physiological saline, whereas the dimethyl sulfoxide (DMSO) group was given 0.1 mL of 1% DMSO orally. The CYC group was administered with 30 mg/kg CYC (i.p.) dissolved in physiological saline, while the SP group received 20 mg/kg SP orally dissolved in DMSO. The SP + CYC combination groups received SP orally at doses of 5, 10, or 20 mg/kg together with 30 mg/kg CYC (i.p.). Additionally, the silymarin (SLY) + CYC group received 50 mg/kg SLY orally and 30 mg/kg CYC (i.p.). The experimental protocol lasted for 10 days. SP treatment alleviated the CYC-induced elevations in plasma AST, ALT, BUN, and creatinine levels. It further suppressed lipid peroxidation by lowering MDA levels and enhanced antioxidant defense by increasing GSH levels and SOD and CAT activities in the liver and kidney. Additionally, SP increased the mRNA expression levels of HO-1, Nrf2, and Bcl-2 while suppressing the elevated expression of NFκB, TNF-α, Bax, and Caspase-3. Furthermore, SP normalized the altered protein expression levels of TNF-α, Caspase-3, and Bax induced by CYC. Histopathological analysis revealed that SP also ameliorated CYC-induced liver and kidney tissue damage. In conclusion, SP markedly attenuated CYC-induced hepatorenal toxicity by inhibiting oxidative stress, inflammation, and apoptosis. These results suggest that SP may represent a promising candidate for preventing liver and kidney injury associated with chemotherapeutic agents.