Niacin ameliorates oxidative stress, inflammation, proteinuria, and hypertension in rats with chronic renal failure

Am J Physiol Renal Physiol. 2009 Jul;297(1):F106-13. doi: 10.1152/ajprenal.00126.2009. Epub 2009 May 6.

Abstract

Significant reduction of renal mass causes progressive deterioration of renal function and structure which is mediated by systemic and glomerular hypertension, hyperfiltration, oxidative stress, inflammation, and dyslipidemia. Niacin is known to improve lipid metabolism and exert antioxidant/anti-inflammatory actions. Therefore, we considered that niacin supplementation may attenuate oxidative stress, inflammation, and tissue injury in the remnant kidney. To this end, 56 nephrectomized [chronic kidney disease (CKD)] rats were randomly assigned to niacin-treated (50 mg x kg(-1) x day(-1) in the drinking water for 12 wk) and untreated groups. Sham-operated rats served as controls. The untreated CKD rats exhibited azotemia, hypertension, hypertriglyceridemia, proteinuria, glomerulosclerosis, tubulointerstitial damage, upregulation of MCP-1, plasminogen activator inhibitor-1 (PAI-1), transforming growth factor (TGF)-beta, cyclooxygenase (COX)-1, COX-2, and NAD(P)H oxidase (NOX-4, gp91(phox), p47(phox) and p22(phox) subunits) and activation of NF-kappaB (IkappaB phosphorylation). Niacin administration reduced MCP-1, PAI-1, TGF-beta, p47(phox), p22(phox), COX-1, and NF-kappaB activation, ameliorated hypertension, proteinuria, glomerulosclerosis, and tubulointerstitial injury. Although niacin lowered serum creatinine and raised creatinine clearance, the differences did not reach statistical significance. Thus niacin supplementation helps to attenuate histological injury and mitigate upregulation of oxidative and inflammatory systems in the remnant kidney.

MeSH terms

  • Animals
  • Chemokine CCL2 / metabolism
  • Creatinine / metabolism
  • Disease Models, Animal
  • Hypertension / drug therapy*
  • Hypertension / etiology
  • Inflammation / drug therapy*
  • Inflammation / etiology
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / drug therapy*
  • Kidney Failure, Chronic / metabolism
  • Male
  • NF-kappa B / metabolism
  • Nephrectomy
  • Niacin / pharmacology
  • Niacin / therapeutic use*
  • Oxidative Stress / drug effects*
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Proteinuria / drug therapy*
  • Proteinuria / etiology
  • Rats
  • Rats, Sprague-Dawley
  • Transforming Growth Factor beta / metabolism
  • Vitamin B Complex / pharmacology
  • Vitamin B Complex / therapeutic use*

Substances

  • Ccl2 protein, rat
  • Chemokine CCL2
  • NF-kappa B
  • Plasminogen Activator Inhibitor 1
  • Transforming Growth Factor beta
  • Vitamin B Complex
  • Niacin
  • Creatinine