title: 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.affiliation: Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.
authors.forename: Muneeb U
authors.initials: MU
authors.lastname: Rehman
authors.forename: Mir
authors.initials: M
authors.lastname: Tahir
authors.forename: Abdul Quaiyoom
authors.initials: AQ
authors.lastname: Khan
authors.forename: Rehan
authors.initials: R
authors.lastname: Khan
authors.lastname: Oday-O-Hamiza
authors.forename: Abdul
authors.initials: A
authors.lastname: Lateef
authors.forename: Syed Kazim
authors.initials: SK
authors.lastname: Hassan
authors.forename: Sumaya
authors.initials: S
authors.lastname: Rashid
authors.forename: Nemat
authors.initials: N
authors.lastname: Ali
authors.forename: Mirza
authors.initials: M
authors.lastname: Zeeshan
authors.forename: Sarwat
authors.initials: S
authors.lastname: Sultana
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D053138:Cyclohexenes / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004317:Doxorubicin / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D000077222:Limonene; D015227:Lipid Peroxidation; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013729:Terpenes / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D053138:Cyclohexenes; D016207:Cytokines; D016328:NF-kappa B; D009573:Nitrites; D020011:Protective Agents; D013729:Terpenes; D004317:Doxorubicin; D000077222:Limonene; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D005978:Glutathione
keywords:   d-limonene; Chemoprevention; doxorubicin; nephrotoxicity