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

Abstract

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.

• Authors: Muneeb U Rehman, Mir Tahir, Abdul Quaiyoom Khan, Rehan Khan, Oday-O-Hamiza, Abdul Lateef, Syed Kazim Hassan, Sumaya Rashid, Nemat Ali, Mirza Zeeshan, Sarwat Sultana
• Journal: Experimental biology and medicine (Maywood, N.J.) (Exp Biol Med (Maywood)) Vol. 239 Issue 4 Pg. 465-76 (Apr 2014) ISSN: 1535-3699 [Electronic] England
• PMID: 24586096 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Biomarkers
• Cyclohexenes
• Cytokines
• NF-kappa B
• Nitrites
• Protective Agents
• Terpenes
• Doxorubicin
• Limonene
• Nitric Oxide Synthase Type II
• Nos2 protein, rat
• Cyclooxygenase 2
• Ptgs2 protein, rat
• Glutathione

Topics

• Animals
• Antioxidants (metabolism)
• Biomarkers (blood)
• Cyclohexenes (pharmacology)
• Cyclooxygenase 2 (genetics, metabolism)
• Cytokines (metabolism)
• Doxorubicin (toxicity)
• Glutathione (metabolism)
• Kidney (drug effects, metabolism)
• Limonene
• Lipid Peroxidation
• NF-kappa B (genetics, metabolism)
• Nitric Oxide Synthase Type II (genetics, metabolism)
• Nitrites (metabolism)
• Oxidative Stress (drug effects)
• Protective Agents (pharmacology)
• Rats
• Rats, Wistar
• Terpenes (pharmacology)