Nesfatin-1 treatment preserves antioxidant status and attenuates renal fibrosis in rats with unilateral ureteral obstruction


Tezcan N., Özdemir-Kumral Z. N. , Yenal N. Ö. , Çilingir-Kaya Ö. T. , Virlan A. T. , Özbeyli D. , ...More

NEPHROLOGY DIALYSIS TRANSPLANTATION, vol.37, pp.1238-1248, 2022 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 37
  • Publication Date: 2022
  • Doi Number: 10.1093/ndt/gfac053
  • Title of Journal : NEPHROLOGY DIALYSIS TRANSPLANTATION
  • Page Numbers: pp.1238-1248
  • Keywords: apoptosis, inflammation, nesfatin-1, oxidative stress, unilateral ureteral obstruction, BLOOD-BRAIN-BARRIER, PROGRESSIVE FIBROSIS, EXPRESSION, INJURY, NEPHROPATHY, DAMAGE, ANTAGONIST, APOPTOSIS, BLOCKADE

Abstract

Background Nesfatin-1 (NES-1), an anorexigenic peptide, was reported to have anti-inflammatory and anti-apoptotic actions in several inflammation models. Methods To elucidate potential renoprotective effects of NES-1, unilateral ureteral obstruction (UUO) was induced in male Sprague Dawley rats by ligating left ureters. The rats were injected intraperitoneally with either saline (SL) or NES-1 (10 mu g/kg/day) for 7 or 14 days (n = 8 in each group). On the 7th or 14th day, obstructed kidneys were removed for the isolation of leucocytes for flow-cytometric analysis and the assessments of biochemical and histopathological changes. Results Opposite to glutathione levels, renal myeloperoxidase activity in the SL-treated UUO group was significantly increased compared with the sham-operated group, while NES-1 treatment abolished the elevation. The percentages of CD8+/CD4+ T-lymphocytes infiltrating the obstructed kidneys were increased in the SL-treated groups but treatment with NES-1 did not prevent lymphocyte infiltration. Elevated tumour necrosis factor-alpha (TNF-alpha) levels in SL-treated UUO group were decreased with NES-1. Although total degeneration scores were similarly increased in all UUO groups, tubular dilatation scores were significantly increased in UUO groups and lowered by NES-1 only in the 7-day treated group. Elevated interstitial fibrosis scores in the SL-treated groups were decreased in both 7- and 14-day NES-1 treated groups, while alpha-smooth muscle actin (alpha-SMA) and apoptosis scores were depressed in both NES-1 treated groups. Conclusion The present data demonstrate that UUO-induced renal fibrosis is ameliorated by NES-1, which appears to involve the inhibition of neutrophil infiltration and thereby amelioration of oxidative stress and inflammation. These data suggest that NES-1 may have a regulatory role in protecting the kidneys against obstruction-induced renal injury.