Beneficial Effects of Dietary Nitrite on a Model of Nonalcoholic Steatohepatitis Induced by High-Fat/High-Cholesterol Diets in SHRSP5/Dmcr Rats: A Preliminary Study

• Published in: International journal of molecular sciences 2022-03, Vol.23 (6), p.2931
• Main Authors: Sonoda, Kunihiro, Kono, Yuka, Kitamori, Kazuya, Ohtake, Kazuo, Shiba, Sachiko, Kasono, Keizo, Kobayashi, Jun
• Format: Article
• Language: English
• Subjects: Adenine; Animals; Blood pressure; Captopril; Captopril - pharmacology; Cardiovascular system; Cholesterol; Cirrhosis; Diet; Diet, High-Fat - adverse effects; Disease Models, Animal; Drinking water; Evaluation; Fibrosis; Heart; Hepatocellular carcinoma; Hepatocytes; High cholesterol diet; High fat diet; Hypertension; Inflammation; Kinases; Liver; Liver - metabolism; Liver cirrhosis; Liver Cirrhosis - drug therapy; Liver Cirrhosis - etiology; Liver diseases; NAD(P)H oxidase; NADPH-diaphorase; Nicotinamide; Nitrites; Non-alcoholic Fatty Liver Disease - drug therapy; Non-alcoholic Fatty Liver Disease - etiology; Non-alcoholic Fatty Liver Disease - metabolism; Oxidative stress; Pathology; Rats; Rats, Inbred SHR; Rodents; Signal transduction; Ventricle
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23062931

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease that leads to liver cirrhosis and hepatocellular carcinoma. Endothelial dysfunction caused by hepatic lipotoxicity is an underlying NASH pathology observed in the liver and the cardiovascular system. Here, we evaluated the effect of dietary nitrite on a rat NASH model. Stroke-prone, spontaneously hypertensive 5/Dmcr rats were fed a high-fat/high-cholesterol diet to develop the NASH model, with nitrite or captopril (100 mg/L, each) supplementation in drinking water for 8 weeks. The effects of nitrite and captopril were evaluated using immunohistochemical analyses of the liver and heart tissues. Dietary nitrite suppressed liver fibrosis in the rats by reducing oxidative stress, as measured using the protein levels of nicotinamide adenine dinucleotide phosphate oxidase components and inflammatory cell accumulation in the liver. Nitrite lowered the blood pressure in hypertensive NASH rats and suppressed left ventricular chamber enlargement. Similar therapeutic effects were observed in a captopril-treated rat NASH model, suggesting the possibility of a common signaling pathway through which nitrite and captopril improve NASH pathology. In conclusion, dietary nitrite attenuates the development of NASH with cardiovascular involvement in rats and provides an alternative NASH therapeutic strategy.