title: Ameliorative effect of naringin in acetaminophen-induced hepatic and renal toxicity in laboratory rats: role of FXR and KIM-1.
abstract: BACKGROUND
  Acetaminophen (APAP) is an analgesic and antipyretic agent commonly known agent to cause hepatic and renal toxicity at a higher dose. Naringin, a bioflavonoid possesses multiple pharmacological properties such as antioxidant, anti-inflammatory, analgesic and anti-hyperlipidemic activity.
  
  
  OBJECTIVE
  To evaluate the effect of naringin against the APAP-induced hepatic and renal toxicity.
  
  
  METHODS
  Male Wistar albino rats (180-220 g) were divided into various groups, and toxicity was induced by APAP (700 mg/kg, p.o., 14 days). Naringin (20, 40 and 80 mg/kg, p.o.) or Silymarin (25 mg/kg) was administered to rats 2 h before APAP oral administration. Various biochemical, molecular and histopathological parameter were accessed in hepatic and renal tissue.
  
  
  RESULTS
  Naringin pretreatment significantly decreased (p < 0.05) serum creatinine, blood urea nitrogen, bilirubin, aspartate transaminase, alanine transaminase, lactate dehydrogenase, low-density lipoprotein, very low-density lipoprotein, cholesterol and triglycerides as compared with APAP control rats. Decreased level of serum albumin, uric acid, and high-density lipoprotein were also significantly restored (p < 0.05) by naringin pretreatment. It also significantly restores (p < 0.05) the altered level of superoxide dismutase, reduced glutathione, malondialdehyde and nitric oxide in hepatic and renal tissue. Moreover, altered mRNA expression of hepatic farnesoid X receptor and renal injury molecule-1 (KIM-1) were significantly restored (p < 0.05) by naringin treatment. Naringin treatment also reduced histological alteration induced by APAP in the liver and kidney.
  
  
  CONCLUSIONS
  Naringin exerts its hepato- and nephroprotective effect via modulation of oxido-nitrosative stress, FXR and KIM-1 mRNA expression.
authors.affiliation: a Department of Pharmacology, Poona College of Pharmacy , Bharati Vidyapeeth Deemed University , Pune , Maharashtra , India.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Adil
authors.affiliation: a Department of Pharmacology, Poona College of Pharmacy , Bharati Vidyapeeth Deemed University , Pune , Maharashtra , India.
authors.forename: Amit D
authors.initials: AD
authors.lastname: Kandhare
authors.affiliation: a Department of Pharmacology, Poona College of Pharmacy , Bharati Vidyapeeth Deemed University , Pune , Maharashtra , India.
authors.forename: Pinaki
authors.initials: P
authors.lastname: Ghosh
authors.affiliation: a Department of Pharmacology, Poona College of Pharmacy , Bharati Vidyapeeth Deemed University , Pune , Maharashtra , India.
authors.forename: Shivakumar
authors.initials: S
authors.lastname: Venkata
authors.affiliation: a Department of Pharmacology, Poona College of Pharmacy , Bharati Vidyapeeth Deemed University , Pune , Maharashtra , India.
authors.forename: Kiran S
authors.initials: KS
authors.lastname: Raygude
authors.affiliation: a Department of Pharmacology, Poona College of Pharmacy , Bharati Vidyapeeth Deemed University , Pune , Maharashtra , India.
authors.forename: Subhash L
authors.initials: SL
authors.lastname: Bodhankar
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D000410:Alanine Transaminase / Q000097:blood; D018712:Analgesics, Non-Narcotic / Q000633:toxicity*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D003404:Creatinine / Q000097:blood; D044950:Flavanones / Q000008:administration & dosage*; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008099:Liver / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014527:Uric Acid / Q000097:blood; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D000082:Acetaminophen; D000410:Alanine Transaminase; D018712:Analgesics, Non-Narcotic; D001219:Aspartate Aminotransferases; D015815:Cell Adhesion Molecules; D003404:Creatinine; D044950:Flavanones; D005978:Glutathione; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008315:Malondialdehyde; D018160:Receptors, Cytoplasmic and Nuclear; D014527:Uric Acid; D000099150:Receptor, Farnesoid X-Activated; C110936:Havcr1 protein, rat; C005274:naringin
keywords: Antioxidant; FXR; KIM-1; hepatic toxicity; naringin; renal toxicity