Nesfatin-1 alleviates extrahepatic cholestatic damage of liver in rats

Abstract

Obstructive jaundice (OJ) can be defined as cessation of bile flow into the small intestine due to benign or malignant changes. Nesfatin-1, recently discovered anorexigenic peptide derived from nucleobindin-2 in hypothalamic nuclei, was shown to have anti-inflammatory and antiapoptotic effects. This study is aimed to investigate the therapeutic effects of nesfatin-1 on OJ in rats. Twenty-four adult male Wistar-Hannover rats were randomly assigned to three groups: sham (n = 8), control (n = 8), and nesfatin (n = 8). After bile duct ligation, the study groups were treated with saline or nesfatin-1, for 10 days. Afterward, blood and liver tissue samples were obtained for biochemical analyses, measurement of cytokines, determination of the oxidative DNA damage, DNA fragmentation, and histopathologic analyses. Alanine aminotransferase and gamma-glutamyl transferase levels were decreased after the nesfatin treatment; however, these drops were statistically non-significant compared to control group (p = 0.345, p = 0.114). Malondialdehyde levels decreased significantly in nesfatin group compared to control group (p = 0.032). Decreases in interleukin-6 and tumor necrosis factor-α levels from the liver tissue samples were not statistically significant in nesfatin group compared to control group. The level of oxidative DNA damage was lower in nesfatin group, however this result was not statistically significant (p = 0.75). DNA fragmentation results of all groups were similar. Histopathological examination revealed that there was less neutrophil infiltration, edema, bile duct proliferation, hepatocyte necrosis, basement membrane damage, and parenchymal necrosis in nesfatin compared to control group. The nesfatin-1 treatment could alleviate cholestatic liver damage caused by OJ due to its anti-inflammatory and antioxidant effects.

Nesfatin-1 ameliorates sepsis-induced remote organ injury: The role of oxidant-antioxidant status and neutrophils

“…In addition, protective effect of nesfatin-1 on gastric (11), intestinal (15), cardiac (17), cerebral (12) and dermal (10) damage was attributed to its role in supporting antioxidant capacity of the related tissues. However, in a cholestatic liver injury model, 10-day nesfatin-1 treatment has decreased hepatic MDA levels and hepatocyte necrosis without significantly altering the oxidative DNA damage (36). In parallel to their results, our data demonstrate that histopathologically verified alleviation of sepsis-induced hepatic injury by nesfatin-1does not appear to involve an antioxidant action, suggesting the presence of other anti-inflammatory mechanisms operating in the hepatic cells, which require further investigation.…”

Beneficial impact of Nesfatin-1 on reproductive dysfunction induced by nicotine in male rats: Possible modulation of autophagy and pyroptosis signaling pathways

“…Interestingly, the present study recorded that in the NTþnesfatin-1 group, nesfatin-1 notably elevated the serum levels of testosterone, LH and FSH, in addition to restoring the activities of the steroidogenic enzymes 3b-HSD and 17b-HSD. This might be ascribed to its anti-apoptotic, anti-inflammatory, antioxidant effects [7,8] and its stimulating effect on autophagy in testicular tissue, as shown in our results. It was reported that autophagy enhances the uptake of cholesterol into the Leydig cells; hence it activates the steroidogenic enzymes with subsequent increase of synthesis of testosterone [11].…”

“…As displayed in our results, nesfatin-1 treatment significantly restored the sperm parameters in NT-treated rats. The restoration of normal sperm parameters by nesfatin-1 might be explained by its antioxidant, anti-apoptotic, anti-inflammatory effects [7,8] and its stimulating effect on autophagy that has a prime role in the conservation of healthy sperms [43], as revealed in our results. The histopatholological analyses of the testicular tissue confirmed our aforementioned findings.…”

“…the hypothalamus, and in peripheral tissues such as the digestive system, adipose tissue and reproductive organs in females and males. Previous studies showed that it has anti-inflammatory, anti-apoptotic and antioxidant effects [7,8].…”

<p>Antioxidant, Anti-Inflammatory and Anti-Apoptotic Activities of Nesfatin-1: A Review</p>

“…101 Because of this, various antioxidants have been tested in experimental obstructive jaundice models. [102][103][104] Solmaz et al 105 found that nesfatin-1 reduced the oxidative damage of the liver through its anti-inflammatory and antioxidant effects, 105 and may become a potential drug for the treatment of obstructive jaundice.…”