title: Betulinic acid attenuates renal oxidative stress and inflammation in experimental model of murine polymicrobial sepsis.
abstract: Sepsis is a common cause of acute kidney injury (AKI) and is associated with substantial morbidity and mortality. Objective of the study was to evaluate the effect of betulinic acid, a triterpenoid in sepsis-induced AKI using cecal ligation puncture (CLP) mouse model. Mice subjected to CLP developed histologic AKI at 18h after CLP. There was an increase in renal proinflammatory response (nuclear factor-kappa B expression, tumor necrosis factor-alpha, interleukin (IL)-6 and IL-10), matrix metalloproteinase-9, plasma creatinine, renal neutrophil gelatinase-associated lipocalin and oxidant stress response (malondialdehyde, inducible nitric oxide synthase, total nitrite and superoxide); decrease in anti-oxidant levels (superoxide dismutase and catalase) at 18h of CLP. However, BA pretreatment at the doses of 10 and 30mg/kg prevented the CLP-induced kidney damage by restoring the aforementioned inflammatory mediators, oxidant and anti-oxidant imbalance. These evidences suggest that, the protective effects of BA on kidney are associated with defending action against inflammatory and oxidative stress response in CLP mice and BA could be potential therapeutic agent in sepsis-induced AKI.
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly, UP 243 122, India.
authors.forename: Madhu Cholenahalli
authors.initials: MC
authors.lastname: Lingaraju
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly, UP 243 122, India.
authors.forename: Nitya Nand
authors.initials: NN
authors.lastname: Pathak
authors.affiliation: Division of Bacteriology and Mycology, Indian Veterinary Research Institute, Izatnagar, Bareilly, UP 243 122, India.
authors.forename: Jubeda
authors.initials: J
authors.lastname: Begum
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly, UP 243 122, India.
authors.forename: Venkanna
authors.initials: V
authors.lastname: Balaganur
authors.affiliation: Division of Animal Biotechnology, Indian Veterinary Research Institute, Izatnagar, Bareilly, UP 243 122, India.
authors.forename: Harish Darasaguppe
authors.initials: HD
authors.lastname: Ramachandra
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly, UP 243 122, India.
authors.forename: Rafia Ahmad
authors.initials: RA
authors.lastname: Bhat
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly, UP 243 122, India.
authors.forename: Mahendra
authors.initials: M
authors.lastname: Ram
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly, UP 243 122, India.
authors.forename: Vishakha
authors.initials: V
authors.lastname: Singh
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly, UP 243 122, India.
authors.forename: Kannan
authors.initials: K
authors.lastname: Kandasamy
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly, UP 243 122, India.
authors.forename: Dhirendra
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly, UP 243 122, India.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly, UP 243 122, India. Electronic address: sktandan@ivri.res.in.
authors.forename: Surendra Kumar
authors.initials: SK
authors.lastname: Tandan
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D060085:Coinfection / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D053978:Pentacyclic Triterpenes; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D000094062:Betulinic Acid
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D000094062:Betulinic Acid
keywords: Cecal ligation and puncture; Cytokines; Inflammation; Oxidative stress; Septic kidney damage; Triterpenoid