title: Therapeutic potential of 7,8-dimethoxycoumarin on cisplatin- and ischemia/reperfusion injury-induced acute renal failure in rats.
abstract: This study was designed to investigate the role of 7,8-dimethoxycoumarin on cisplatin- and ischemia/reperfusion (I/R)-induced acute renal failure in rats. Acute renal failure was induced in rats by administration of a single dose of cisplatin (CP) (6 mg/kg, intraperitoneally on day 6) and occlusion of the left renal artery for 45 min (I) and opened for the next 24 h (R). The drug samples of 7,8-dimethoxycoumarin (DMC, 50, 75, and 100 mg/kg) and cyclosporin A (50 μM/kg) were administered orally for six consecutive days. Administration of a single dose of cisplatin and I/R event has significantly raised blood urea nitrogen and creatinine, N-acetyl beta-D: -glucosaminidase, and thiobarbituric acid reactive substances but decreased FrNa, creatinine clearance, reduced glutathione (GSH), mitochondrial cytochrome c oxidase, and adenosine triphosphate levels. Further, pretreatment of DMC (50, 75, and 100 mg/kg, p.o., for six consecutive days) has ameliorated the CP- and I/R-induced biochemical and histopathological changes in a dose-dependent manner. Furthermore, 75 and 100 mg/kg of 7,8-dimethoxycoumarin has shown to possess the significant renoprotective effect similar to that of the cyclosporin A-treated group which served as positive control. Based on the results of the present study, it has been concluded that 7,8-dimethoxycoumarin protects the kidney against the CP and I/R injury via antioxidant, anti-inflammatory, and inactivation of mitochondrial permeability transition pore opening.
authors.affiliation: Department of Pharmaceutical Chemistry, Rayat Institute of Pharmacy, Near Railmajra, Ropar 144533 Punjab, India. arunachalammu@gmail.com
authors.forename: Arunachalam
authors.initials: A
authors.lastname: Muthuraman
authors.forename: Shailja
authors.initials: S
authors.lastname: Sood
authors.forename: Muthusamy
authors.initials: M
authors.lastname: Ramesh
authors.forename: Karan Deep Singh
authors.initials: KD
authors.lastname: Puri
authors.forename: Anil
authors.initials: A
authors.lastname: Peters
authors.forename: Ashish
authors.initials: A
authors.lastname: Chauhan
authors.forename: Pradeep Kumar
authors.initials: PK
authors.lastname: Arora
authors.forename: Ajay
authors.initials: A
authors.lastname: Rana
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000627:therapeutic use*; D000975:Antioxidants / Q000302:isolation & purification / Q000627:therapeutic use*; D002945:Cisplatin; D002957:Citrus; D003374:Coumarins / Q000302:isolation & purification / Q000627:therapeutic use*; D003576:Electron Transport Complex IV / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D010936:Plant Extracts / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D003374:Coumarins; D010936:Plant Extracts; D017392:Thiobarbituric Acid Reactive Substances; C049928:7,8-dimethoxycoumarin; D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV; D002945:Cisplatin