The outcome of ketogenic diets on the liver and the protecting role of atorvastatin: A histological, immunohistochemical and ultrastructural study

Abstract

The current study investigated structural and functional modifications of the liver following long-term ketogenic diet (KD) and every-otherday ketogenic diet (EODKD) usage. The probable role of atorvastatin (ATO) in the adjustment process was also investigated. It was carried out on 24 Sprague-Dawley rats, which were divided into four groups: control, KD, EODKD, and ATO. Various biochemical, histological, and immunohistochemical analysis were performed on the liver. The blood was tested for aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglycerides, cholesterol, inflammatory markers, Bax, BCL2, NLRP3 inflammasome, and oxidative stress markers. KDs induced damages to the liver mainly due to oxidative stress (increase TBARS, MDA/decrease SOD/GSH) and inflammation. In addition, the hepatic triglycerides and cholesterol levels are decreased. The KD group was worse off than the EODKD group. ATO administered concurrently with KD preserved liver architecture, reduced oxidative stress, normalized NLRP3, and further reduced intrahepatic triglycerides and cholesterol levels. Both KD and EODKD cause structural liver damage that is accompanied by an elevation of hepatic markers (AST and ALT) and a decrease in hepatic triglycerides, hepatic cholesterol, and serum cholesterol. KD has a more destructive effect. Oxidative stress, inflammation, and high fat concentrations are contributing factors to hepatic injury in these diets. ATO with KD is beneficial.