Department of Food and Nutritional Environment, College of Human Life and Environment, Kinjo Gakuin University, Nagoya 463-8521, Japan.
Division of Physiology, School of Pharmaceutical Sciences, Faculty of Pharmaceutical Science, Josai University, Saitama 350-0248, Japan.
Int J Mol Sci. 2022 Mar 8;23(6):2931. 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.
非酒精性脂肪性肝炎（NASH）是一种慢性肝病，可导致肝硬化和肝细胞癌。肝脂肪毒性引起的内皮功能障碍是在肝脏和心血管系统中观察到的 NASH 病理学的潜在原因。在这里，我们评估了饮食中亚硝酸盐对大鼠 NASH 模型的影响。易发生中风的自发性高血压 5/Dmcr 大鼠喂食高脂肪/高胆固醇饮食以建立 NASH 模型，同时在饮用水中补充亚硝酸盐或卡托普利（各 100mg/L）8 周。使用肝脏和心脏组织的免疫组织化学分析评估亚硝酸盐和卡托普利的作用。饮食中亚硝酸盐通过降低氧化应激来抑制大鼠的肝纤维化，这可以通过烟酰胺腺嘌呤二核苷酸磷酸氧化酶成分的蛋白水平和肝脏中炎症细胞的积累来衡量。亚硝酸盐降低了 NASH 高血压大鼠的血压并抑制了左心室腔扩大。在卡托普利治疗的大鼠 NASH 模型中观察到类似的治疗效果，表明亚硝酸盐和卡托普利通过共同的信号通路改善 NASH 病理学的可能性。总之，饮食中亚硝酸盐可减轻伴有心血管受累的大鼠 NASH 的发展，并为 NASH 的治疗提供了一种替代策略。
