Monkfish (Lophius litulon) Peptides Ameliorate High-Fat-Diet-Induced Nephrotoxicity by Reducing Oxidative Stress and Inflammation via Regulation of Intestinal Flora.

BACKGROUND: Renal damage and intestinal flora imbalance due to lipotoxicity are particularly significant in terms of oxidative stress and inflammation, which can be alleviated with bioactive peptides. The monkfish (Lophius litulon) is rich in proteins, which can be used as a source of quality bioactive peptides. This study aimed to examine the protective effect of monkfish peptides on renal injury and their potential role in regulating gut microbiota. METHODS: Monkfish meat was hydrolyzed using neutral protease and filtered, and the component with the highest elimination rate of 2,2-diphenyl-1-picrylhydrazyl was named lophius litulon peptides (LPs). Lipid nephrotoxicity was induced via high-fat diet (HFD) feeding for 8 weeks and then treated with LPs. Oxidative stress, inflammatory factors, and intestinal flora were evaluated. RESULTS: LP (200 mg/kg) therapy reduced serum creatinine, uric acid, and blood urea nitrogen levels by 49.5%, 31.6%, and 31.6%, respectively. Renal vesicles and tubules were considerably improved with this treatment. Moreover, the activities of superoxide dismutase, glutathione peroxidase, and total antioxidant capacity increased significantly by 198.7%, 167.9%, 61.5%, and 89.4%, respectively. LPs attenuated the upregulation of HFD-induced Toll-like receptor 4 and phospho-nuclear factor-kappa B and increased the protein levels of heme oxygenase 1, nicotinamide quinone oxidoreductase 1, and nuclear factor erythroid 2-related factor 2. The dysbiosis of intestinal microbiota improved after LP treatment. CONCLUSIONS: LPs significantly improve antioxidant activity, reduce inflammatory cytokine levels, and regulate intestinal dysbiosis. Thus, LPs are potential compounds that can alleviate HFD-induced renal lipotoxicity.

Using Collagen Peptides From the Skin of Monkfish (Lophius litulon) to Ameliorate Kidney Damage in High-Fat Diet Fed Mice by Regulating the Nrf2 Pathway and NLRP3 Signaling.

BACKGROUND: Oxidative stress and inflammation play important roles in high-fat diet (HFD) induced kidney damage. Previous studies show that the collagen extracted from the skin of monkfish (Lophius litulon) with pepsin (pepsin-solubilized collagen, PSC) exhibits good biological activities. This study investigates the protective effect of PSCP against chronic kidney injury in HFD-fed mice. METHODS: Pepsin-solubilized collagen was further hydrolyzed into collagen peptides, and the compound with the best 2,2-diphenyl-1-picrylhydrazyl (DPPH) clearance rate was named pepsin-solubilized collagen peptide (PSCP). A group of mice were fed an HFD for 4 weeks, and then for another 6 weeks PSCP was added to their diet at the amount of either 100 or 200 mg/kg. RESULTS: Pepsin-solubilized collagen peptide treatment (200 mg/kg) reduced the mice's serum levels of uric acid (UA), creatinine (CRE), and blood urea nitrogen (BUN) by 27, 20, and 37%, respectively. This treatment also remarkably improved renal histopathology. Moreover, the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) were increased by 96, 52, and 74%, respectively, and decreased the malondialdehyde (MDA) level by 36%. Additionally, PSCP activated the Nrf2 pathway and inhibited NLRP3 signaling to significantly reduce the levels of inflammatory cytokines IL-1ß, IL-6, and TNF-α. CONCLUSIONS: Our results indicate that compound PSCP has the potential to prevent or control chronic kidney damage.