Inhibition of NF-κB/TNF-α pathway may be involved in the protective effect of resveratrol against cyclophosphamide-induced multi-organ toxicity

Abstract

Context: Cyclophosphamide (CyP), an efficient anticancer drug, may damage normal human cells. Resveratrol (RES), a natural polyphenol, has a diverse pharmacological properties.Objective: To test possible protective effect of RES on multi-organ damage caused by CyP.Materials and methods: RES (10 mg/kg/day) was administered orally for 8 days. In independent rat groups, CyP toxicity was induced via a single dose of 150 mg/kg i.p. 3 days before the end of experiment, with or without RES treatment.Results: Compared to control, CyP caused significant increase in organ-to-body weight ratios of heart, kidney and liver, with deterioration in their functional parameters; namely serum creatine kinase, blood urea nitrogen, creatinine, alanine aminotransferase and aspartate aminotransferase. CyP also caused distortion in these organs' histology, with significant tissue oxidative stress, manifested by decrease in reduced glutathione and catalase, as well as increase in malondialdehyde and nitric oxide levels. Furthermore, CyP caused multi-organ inflammatory effects as shown by increased tumor necrosis factor-α levels, as well as up-regulation of nuclear factor-κB expressions. Using RES concurrently with CyP restored heart, kidney and liver functional parameters, as well as their normal histology. RES also reversed oxidative stress, as well as inflammatory signs caused by CyP alone.Conclusions: RES may be beneficial adjuvant that confers multi-organ protection against CyP toxicity via antioxidant and anti-inflammatory mechanisms.