Naringin ameliorates sodium arsenite-induced renal and hepatic toxicity in rats: decisive role of KIM-1, Caspase-3, TGF-β, and TNF-α.
Chronic exposure of a naturally occurring metal arsenic leads to renal and hepatic diseases. Naringin, a flavanone glycoside, possesses anti-inflammatory and anti-oxidant potential. The aim of this investigation was to evaluate the protective effect of naringin against arsenic-induced renal and hepatic toxicity in rats. Renal and hepatic toxicity was induced in rats by sodium arsenite (5 mg/kg, p.o.). Rats were treated orally with either vehicle or naringin (20, 40, and 80 mg/kg) or Coenzyme Q10 (10 mg/kg) for 28 days. Various biochemical, histological, and molecular biomarkers were assessed in kidney and liver. Treatment with naringin (40 and 80 mg/kg) significantly and dose-dependently restored (p < 0.01 and p < 0.001) altered levels of kidney (serum creatinine, urine creatinine, BUN, uric acid, and creatinine clearance) and liver function test (AST and ALT) induced by sodium arsenite. Elevated levels of oxido-nitrosative stress in renal and hepatic tissue was significantly and dose-dependently decreased (p < 0.01 and p < 0.001) by naringin (40 and 80 mg/kg) treatment. It significantly and dose-dependently down-regulated (p < 0.01 and p < 0.001) renal KIM-1, Caspase-3, TGF-β, and TNF-α mRNA expression. Histopathological alteration induced in kidney and liver by sodium arsenite was reduced by naringin (40 and 80 mg/kg) treatment. In conclusion, naringin treatment ameliorates arsenic-induced renal and hepatic damage in rats due its antioxidant and anti-inflammatory properties via down-regulation of elevated oxido-nitrosative stress, KIM-1, Caspase-3, TGF-β, and TNF-α levels.
a Department of Pharmacology , Poona College of Pharmacy, Bharati Vidyapeeth Deemed University , Pune , Maharashtra , India.
Mohammad
M
Adil
a Department of Pharmacology , Poona College of Pharmacy, Bharati Vidyapeeth Deemed University , Pune , Maharashtra , India.
Amit D
AD
Kandhare
a Department of Pharmacology , Poona College of Pharmacy, Bharati Vidyapeeth Deemed University , Pune , Maharashtra , India.
Asjad
A
Visnagri
a Department of Pharmacology , Poona College of Pharmacy, Bharati Vidyapeeth Deemed University , Pune , Maharashtra , India.
Subhash L
SL
Bodhankar
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D018053:Arsenites / Q000633:toxicity*; D053148:Caspase 3 / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D044950:Flavanones / Q000008:administration & dosage*; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D007677:Kidney Function Tests; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008111:Liver Function Tests; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017670:Sodium Compounds / Q000633:toxicity*; D016212:Transforming Growth Factor beta / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000975:Antioxidants; D018053:Arsenites; D053148:Caspase 3; D015815:Cell Adhesion Molecules; D044950:Flavanones; D017670:Sodium Compounds; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C110936:Havcr1 protein, rat; C017947:sodium arsenite; C505410:Casp3 protein, rat; C005274:naringin
Caspase-3; KIM-1; Naringin; TGF-β; TNF-α; renal toxicity; sodium arsenite