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. 2022 Jun 23;37(7):1238-1248.
doi: 10.1093/ndt/gfac053.

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

Neslihan Tezcan  1 , Zarife Nigâr Özdemir-Kumral  2 , Naziye Özkan Yenal  3 , Özlem T Çilingir-Kaya  4 , Aysin Tulunay Virlan  5 , Dilek Özbeyli  3 , Şule Çetinel  4 , Berrak Ç Yeğen  2 , Mehmet Koç  2   6
Affiliations

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

Neslihan Tezcan et al. Nephrol Dial Transplant. .

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 µg/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-α) 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 (α-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.

Keywords: apoptosis; inflammation; nesfatin-1; oxidative stress; unilateral ureteral obstruction.

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