d-limonene suppresses doxorubicin-induced oxidative stress and inflammation via repression of COX-2, iNOS, and NFκB in kidneys of Wistar rats

d-limonene is a naturally occurring monoterpene and has been found to posses numerous therapeutic properties. In this study, we used d-limonene as a protective agent against the nephrotoxic effects of anticancer drug doxorubicin (Dox). Rats were given d-limonene at doses of 5% and 10% mixed with diet for 20 consecutive days. Dox was give at the dose of 20 mg/kg body weight intraperitoneally. The protective effects of d-limonene on Dox-induced oxidative stress and inflammation were investigated by assaying oxidative stress biomarkers, lipid peroxidation, serum toxicity markers, proinflammatory cytokines, and expression of nuclear factor kappa B (NFκB), cyclo-oxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) and Nitrite levels. Administration of Dox (20 mg/kg body weight) in rats enhanced renal lipid peroxidation; depleted glutathione content and anti-oxidant enzymes; elevated levels of kidney toxicity markers viz. kidney injury molecule-1 (KIM-1), blood urea nitrogen (BUN), and creatinine; enhanced expression of NFκB, COX-2, and iNOS and nitric oxide. Treatment with d-limonene prevented oxidative stress by restoring the levels of antioxidant enzymes, further both doses of 5% and 10% showed significant decrease in inflammatory response. Both the doses of d-limonene significantly decreased the levels of kidney toxicity markers KIM-1, BUN, and creatinine. d-limonene also effectively decreased the Dox induced overexpression of NF-κB, COX-2, and iNOS and nitric oxide. Data from the present study indicate the protective role of d-limonene against Dox-induced renal damage.