title: TNF-α, IL-6 and IL-10 expressions, responsible for disparity in action of curcumin against cisplatin-induced nephrotoxicity in rats.
abstract: Cisplatin is a regularly employed effective chemotherapeutic agent for the treatment of many types of cancer. The main drawback of cisplatin treatment is kidney toxicity which affects 25-35% of treated patients. Many mechanisms are believed to be involved in this kidney damage, but inflammation plays a significant role in this event. Curcumin is a polyphenol and has antioxidant and anti-inflammatory effects. The purpose of this study was to determine the protective effects of curcumin on cisplatin-induced nephrotoxicity. Female rats were randomly divided into 5 groups: control, curcumin, cisplatin, curcumin plus cisplatin (pre-treatment group) and cisplatin plus curcumin (post-treatment group). Rats were given cisplatin (7.5 mg/kg body weight) with or without curcumin treatment (120 mg/kg body weight). Blood urea nitrogen (BUN), creatinine, albumin, tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, IL-10 expressions and histological changes were determined on the 5th day after cisplatin injection. Acute kidney damage was evident by increased BUN and creatinine levels. In addition, cisplatin showed a marked pro-inflammatory response as revealed by a significant increase in the tissue levels of TNF-α, IL-6, IL-8 and decrease in the IL-10 level. Pre-treatment of curcumin reduced cisplatin-induced nephrotoxicity which was clearly evident from the reduced BUN, creatinine, TNF-α, IL-6 and IL-8 levels and increased albumin and IL-10 levels. Additionally, these findings were also supported by histopathology of the kidneys. In contrast, post-treatment of curcumin failed to cut down the expression of inflammatory markers substantially and also neglected to increase the expression of IL-10. The disparity in the action of curcumin after pre- and post-treatment with cisplatin-induced nephrotoxicity was due to the inability of post-treatment to reduce TNF-α & IL-6, besides to show a concurrent rise in IL-10 expression in renal tissues.
authors.affiliation: Laboratory of Molecular Pharmacology and Toxicology, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam, 781032, India. parveen5niper@gmail.com.|Department of Pharmacology, Pandit Jawahar Lal Nehru Government Medical College Chamba, Chamba, 176324, Himachal Pradesh, India. parveen5niper@gmail.com.
authors.forename: Parveen
authors.identifier: http://orcid.org/0000-0002-5750-9663
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Laboratory of Neuroscience, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam, 781032, India.
authors.forename: Kunjbihari
authors.initials: K
authors.lastname: Sulakhiya
authors.affiliation: Department of Pharmacology and Toxicology, College of Veterinary Science, Assam Agricultural University, Khanapara, Guwahati, Assam, 781032, India.
authors.forename: Chandana C
authors.initials: CC
authors.lastname: Barua
authors.affiliation: Laboratory of Molecular Pharmacology and Toxicology, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam, 781032, India.
authors.forename: Nitin
authors.initials: N
authors.lastname: Mundhe
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D000818:Animals; D002945:Cisplatin / Q000009:adverse effects* / Q000494:pharmacology; D003474:Curcumin / Q000494:pharmacology*; D005260:Female; D016753:Interleukin-10 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D003474:Curcumin; D002945:Cisplatin
keywords: Cisplatin; Curcumin; Cytokine; Inflammation; Nephrotoxicity