Role of some natural anti-oxidants in the down regulation of Kim, VCAM1, Cystatin C protein expression in lead acetate-induced acute kidney injury

Pharmacol Rep. 2020 Apr;72(2):360-367. doi: 10.1007/s43440-020-00072-8. Epub 2020 Feb 27.

Abstract

Background: Lead is a dangerous systemic toxicant and can provoke life-threatening renal injury. The plan of this study was to evaluate the potential impact of curcumin (CRMN) and L-ascorbic acid (L-ascb) alone or together to counteract lead acetate (Pb-acetate)-induced renal damage in rats and to find out the underlying mechanisms of action of these nutraceuticals.

Methods: Pb-acetate (100 mg/kg/day, i.p.) was injected in male rats along with L-ascb (250 mg/kg/day) and/or CRMN (200 mg/kg/day) orally for 7 days.

Results: Pb-acetate administration increased serum urea, creatinine and uric acid. Renal tissue showed a marked depletion in reduced glutathione level and superoxide dismutase activity and elevation in nitric oxide and malondialdehyde levels. Serum C-reactive protein and IL-1β levels were elevated. Up-regulation of the expression of kidney injury molecule, vascular adhesion molecule-1 and Cystatin C were noticed after Pb-acetate administration. DNA fragmentation was also increased in renal tissues. Histopathological examination revealed a destructed partial layer of Bowman's capsule, proximal and distal convoluted tubules. Treatment with the aforementioned antioxidants ameliorated most of the altered measured biomarker levels.

Conclusion: Interestingly, the combination of L-ascb and CRMN showed the superlative protective effect against Pb-acetate-induced nephrotoxicity.

Keywords: Curcumin; Cystatin C; DNA fragmentation; L-ascorbic acid; Pb-acetate; Vascular adhesion molecule-1.

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / prevention & control*
  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / therapeutic use*
  • Ascorbic Acid / administration & dosage
  • Ascorbic Acid / therapeutic use
  • Cell Adhesion Molecules / genetics
  • Curcumin / administration & dosage
  • Curcumin / therapeutic use
  • Cystatin C / genetics*
  • Down-Regulation
  • Drug Synergism
  • Gene Expression / drug effects*
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Function Tests
  • Lead / toxicity*
  • Male
  • Organometallic Compounds / toxicity*
  • Rats, Wistar
  • Vascular Cell Adhesion Molecule-1 / genetics

Substances

  • Antioxidants
  • Cell Adhesion Molecules
  • Cystatin C
  • Havcr1protein, rat
  • Organometallic Compounds
  • Vascular Cell Adhesion Molecule-1
  • Lead
  • Curcumin
  • Ascorbic Acid
  • lead acetate