title: Ameliorative effect of berberine against gentamicin-induced nephrotoxicity in rats via attenuation of oxidative stress, inflammation, apoptosis and mitochondrial dysfunction.
abstract: BACKGROUND
  Gentamicin (GM) is the commonly used antibiotics against Gram-negative infection, but the nephrotoxic potential of drug limit its clinical interest. The aim of this study was to investigate the protective effect of berberine (BER) against GM-induced nephrotoxicity and possible underlying mechanisms.
  
  
  METHODS
  The rats were divided into various group, namely normal, GM-control, GM + BER (10, 20, and 40 mg/kg). Nephrotoxicity was induced by intraperitoneal administration of GM (120 mg/kg) for 7 consecutive days. BER (10, 20, and 40 mg/kg; p.o.) was also administered for the 7 days. Various biochemical, molecular, and histological parameters were assessed in serum and kidney.
  
  
  RESULTS
  GM-administration significantly increased (p < 0.001) the serum creatinine and blood urea nitrogen (BUN) as well as renal malonaldehyde (MDA), nitric oxide (NO) along with Kidney Injury Molecule-1 (KIM-1), Neutrophil gelatinase-associated lipocalin (NGAL), and nuclear factor-kappa B (NF-KB) renal mRNA expressions. In addition, GM also significantly decreased (p < 0.001) the renal superoxide dismutase (SOD), reduced glutathione (GSH), B-cell lymphoma 2 (Bcl-2) mRNA expression, and mitochondrial enzymes (NADH dehydrogenase and cytochrome c oxidase) activities. Rats treated with BER (20 and 40 mg/kg; p.o.) significantly and dose-dependently (p < 0.05 and p < 0.01) restore the altered levels of antioxidant, inflammatory, apoptosis, AKI markers as well as depleted mitochondrial enzymes. Histopathological abbreviations were also ameliorated by BER administration.
  
  
  CONCLUSIONS
  Berberine exerts renoprotective effects through its anti-oxidant, anti-inflammatory, and anti-apoptotic properties.[Formula: see text].
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: Gautami
authors.initials: G
authors.lastname: Dalvi
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: D000209:Acute-Phase Proteins / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D001599:Berberine / Q000494:pharmacology*; D001806:Blood Urea Nitrogen; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D064420:Drug-Related Side Effects and Adverse Reactions / Q000517:prevention & control*; D005839:Gentamicins / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D007677:Kidney Function Tests; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000209:Acute-Phase Proteins; D000900:Anti-Bacterial Agents; D001599:Berberine; D015815:Cell Adhesion Molecules; D003404:Creatinine; D005839:Gentamicins; D005978:Glutathione; D000071068:Lipocalin-2; D054834:Lipocalins; D008315:Malondialdehyde; D011518:Proto-Oncogene Proteins; D013482:Superoxide Dismutase; C110936:Havcr1 protein, rat; C097278:Lcn2 protein, rat
keywords: Bcl-2; KIM-1; NF-KB; NGAL; berberine; gentamicin; nephrotoxicity