title: Betulinic acid attenuates renal fibrosis in rat chronic kidney disease model.
abstract: BACKGROUND
  Most chronic kidney diseases (CKDs), regardless of the nature of the initial injury, progress to end-stage renal disease (ESRD) characterized by fibrosis with irreversible loss of tissue and function. Thus, improved and more effective therapies are critical. Betulinic acid (BA), a pentacyclic triterpene is a compound in the pipeline of anti-cancer drug development. It has been shown to a possess variety of beneficial effects in many disease conditions. However, its efficacy against CKD is yet to be explored.
  
  
  OBJECTIVE
  The present study was undertaken to investigate the effect of BA on renal fibrosis in the rat model of adenine-induced CKD.
  
  
  RESULTS
  CKD rats gained significantly less weight during the experimental period when compared to control rats and BA treatment did not significantly increase the weight gain in CKD rats. CKD rats showed elevated levels of serum blood urea nitrogen (BUN), creatinine and uric acid along with increased levels of kidney injury markers such as cystatin C and neutrophil gelatinase-associated lipocalin (NGAL). Further, in comparison to control rats, kidney samples from CKD rats revealed increased profibrotic protein levels like transforming growth factor-beta (TGF-β), connective tissue growth factor (CTGF), fibronectin, collagen type I and hydroxyproline indicating a progressive fibrotic response. These data are further fortified by histological findings where kidney damage and fibrosis are clearly evident as dilatation of tubules, glomerular degeneration and vacuolation along with deposition of collagen fibers. However, the above-mentioned findings in CKD rats were significantly reversed by BA-treatment revealing its nephroprotective potential and anti-fibrotic activity.
  
  
  CONCLUSIONS
  The biochemical mechanism of the nephroprotective and anti-fibrotic effect of BA in the adenine-induced CKD rats might be mediated by inhibition of pro-fibrotic protein production thereby hindering the kidney tissue damage along with improvement in kidney function. Thus, BA could be an adjunct agent to retard fibrosis in CKD subjects.
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243 122, UP, India.
authors.forename: Anshuk
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243 122, UP, India.
authors.forename: Richa
authors.initials: R
authors.lastname: Thakur
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243 122, UP, India. Electronic address: maddyvet@gmail.com.
authors.forename: Madhu C
authors.initials: MC
authors.lastname: Lingaraju
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243 122, UP, India.
authors.forename: Dhirendra
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Centre for Wildlife Conservation Management and Disease Surveillance, Indian Veterinary Research Institute, Izatnagar, 243 122, UP, India.
authors.forename: Karikalan
authors.initials: K
authors.lastname: Mathesh
authors.affiliation: CADRAD, Indian Veterinary Research Institute, Izatnagar, 243 122, UP, India.
authors.forename: Avinash G
authors.initials: AG
authors.lastname: Telang
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243 122, UP, India.
authors.forename: Thakur Uttam
authors.initials: TU
authors.lastname: Singh
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243 122, UP, India.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Kumar
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005355:Fibrosis / Q000188:drug therapy* / Q000517:prevention & control; D005786:Gene Expression Regulation / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D015394:Molecular Structure; D009929:Organ Size / Q000187:drug effects; D053978:Pentacyclic Triterpenes; D051381:Rats; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy*; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*; D000094062:Betulinic Acid
chemical_list: D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D000094062:Betulinic Acid
keywords: Chronic kidney disease; Collagen; Fibrosis; Rats; Transforming growth factor-beta