Ameliorative Effects of Theophylline in Combination with Curcumin on Cyclophosphamide-Induced Oxidative Stress and Genotoxicity in Rats

Cyclophosphamide-induced toxicity, including oxidative stress and genotoxicity, is the major concern of cancer chemotherapy therapy. Additional antioxidant supplementation may prevent such a risk. Therefore, in the present study, we assessed the ameliorative effects of theophylline in combination with curcumin on cyclophosphamide-induced oxidative stress and genotoxicity in rats. Wistar albino rats (150-200g) were randomly selected and treated with either distilled water (10 ml/kg), theophylline (20, 50, or 75 mg/kg/day, i.p.), or theophylline + curcumin (25 + 100, 50 + 100, or 75 + 100 mg/kg/day, i.p.) in their respective groups for seven days. After one hour of the last dosing, animals received Cyclophosphamide (10 ml/kg, i.p.) for toxicity induction. Genotoxicity in animals was assessed by the determination of micronucleated bone marrow cells, oxidative stress was evaluated by the determination of enzymatic antioxidant activity (catalase and superoxide dismutase) and the level of lipoperoxidation (malondialdehyde), and liver toxicity was assessed by measuring the serum alanine aminotransferase and aspartate aminotransferase. The results showed that theophylline and its combination with curcumin had significant (<img src=image/17340001_01.gif><0.05) beneficial effects as compared to the Cyclophosphamide control group. They considerably reduced the micronucleated bone marrow cells and restored the oxidative stress and serum liver biomarkers. Additionally, results indicated the potential beneficial effects in the combination group, especially in the theophylline + curcumin (75+100 mg/kg) group to manage the cyclophosphamide-induced toxicity. These results suggest that the combination of curcumin and theophylline enhances the protective effects.