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

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 leukocytes for flow-cytometric analysis and for 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 to sham-operated group, while NES-1 treatment abolished the elevation. The percentages of CD8+/CD4+ T-lymphocytes infiltrating the obstructed kidneys were increased in SL-treated groups but treatment with NES-1 did not prevent lymphocyte infiltration. Elevated TNF-a levels in SL-treated UUO group was 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.

Nesfatin-1 mitigates calcific aortic valve disease via suppressing ferroptosis mediated by GSH/GPX4 and ZIP8/SOD2 axes

“…Recent studies have demonstrated the antioxidant properties of Nesfatin-1, highlighting its involvement in the development and progression of various diseases [29]. For instance, Nesfatin-1 has been shown to preserve antioxidant status and attenuate renal fibrosis in rats with unilateral ureteral obstruction [30]. Additionally, treatment with Nesfatin-1 has been found to alleviate cerebral ischemia-reperfusion injury by inhibiting neuronal cell death and enhancing antioxidant defenses [31].…”

Nesfatin‐1 alleviates hyperoxia‐induced bronchopulmonary dysplasia (BPD) via the nuclear factor‐κB (NF‐κB) p65 signaling pathway

“…It also suppresses free radical formation. [27,38] On the other hand, Nesfatin-1 inhibits inflammation by modulation of various inflammation-related signaling pathways, including the NF-κB pathway, Akt/GSK-3β pathway, and CREB signaling pathway. This leads to a decrease in the subsequent release of inflammatory mediators such as IL-1β and TNF-α.…”

Research progress on the mechanism of renal interstitial fibrosis in obstructive nephropathy

“…Dapagliflozin attenuated renal fibrosis by inhibiting RIP1-RIP3-MLKL signaling pathway-mediated necroinflammation in unilateral ureteral obstruction [ 79 ]. Nesfatin-1 (NES-1) ameliorated UUO-induced renal fibrosis, which may be associated with the inhibition of neutrophil infiltration, thereby ameliorating oxidative stress and inflammation [ 80 ]. Dual soluble epoxide hydrolase inhibitor-PPAR-γ agonist (RB394) alleviated renal fibrosis by reducing renal inflammation, oxidative stress, tubular injury and vascular injury [ 81 ].…”