Differential Therapeutic Effects of Crataegus aronia and Simvastatin on the Hepatocyte Ultrastructure in Hepatic Steatosis

Abstract

SUMMARY:Complications of fat accumulation in liver, hepatic steatosis such as liver cirrhosis and liver failure are among the common public health problems. We sought to investigate the damage to the hepatocyte ultrastructure induced by high fat diets (HFD) and compared the therapeutic effects at the cellular level of two antioxidant and lipid lowering agents; Crataegus aronia extracts and simvastatin on hepatic steatosis. Rats were either fed with HFD (model group) or low fat diets (LFD) (control group) for 15 weeks before being sacrificed and therapeutic groups started the treatment with these agents after week 11 until the sacrifice day. Harvested liver tissues were examined using transmission electron microscopy (TEM) and liver homogenates were assayed for markers of antioxidative stress that are known to be modulated in liver injury. TEM examinations of the model group showed a profound damage to the hepatocytes compared to the control group as demonstrated by steatosis, damaged mitochondria and vaculated cytoplasm, disrupted rough and smooth endoplasmic reticulum and nuclear membrane, dilated intercellular space between hepatocytes, and alterations in lysosomes. In addition, HFD ameliorated the anti-oxidant glutathione (GSH) and augmented the oxidative stress TBARS biomarkers. Both Crataegus aronia and simvastatin significantly reduced lipids and TBARS, and treated damage to hepatic cells, but hepatocyte structures were differentially responded to these agents. However, only Crataegus aronia induced GSH (p=0.001). We conclude that HFD-induced hepatic steatosis caused a substantial damage to the hepatocyte's ultrastructures, and Crataegus aronia and simvastatin treatments differentially reversed hepatic injuries.

Vitamin E Protects Against Hepatocyte Ultrastructural Damage Induced by High Fat Diet in a Rat Model of Pre-Diabetes

“…Similarly, our data that point to the elevation of MDA, TNF-α, and dyslipidemia in pre-diabetes-induced NAFLD (Figs. 1 and 3) are in agreement with our recent reports (Al Humayed et al, 2017;Dallak, 2018;Dallak et al, 2018) and others (Noeman et al, 2011;Oh et al, 2014). However, conflicting data on the beneficial therapeutic use of vitamin E to treat NAFLD and NASH in humans were reported (Townsend & Newsome, 2017).…”

Cinnamon Reduces Dyslipidemia and Liver Steatosis Induced by High Fat Diet in Albino Rats: Histological, Ultrastructural, and Biochemical Studies

“…Most of hepatocytes of HFD-fed rats appeared with abnormal nuclei, irregular nuclear envelope, degenerated mitochondria, dilated rough endoplasmic reticulum, large number of lysosomes, and rarified cytoplasm, in addition to accumulation of lipid droplets that increased in size forming large lipid vacuoles. Similarly, Abd Ellatif et al [22] and Al Humayed et al [23] found similar ultrastructural observations and indicating that HFD induced NAFLD in rats causing steatosis that damaged the ultrastructure of the hepatocytes possibly via augmentation of lipid and oxidative stress. Ahishali et al [24] found similar ultrastructural features in nonalcoholic fatty liver in humans and reported that hepatosteatosis impaired oxidative phosphorylation and leading to increase the levels of ROS, inflammation, fibrosis, and mitochondrial abnormalities.…”

Potential Roles and Key Mechanisms of Hawthorn Extract against Various Liver Diseases

“…C. aronia and C. monogyna attenuated hepatic fat content by regulating hepatic GSH and TBARS and hepatic total thiol molecules, respectively, in Wistar rats [30,37]. Specifically, the antioxidant activity of 200 mg/kg C. aronia was more potent than that of 4 mg/kg of simvastatin [37] (Figure 2, Table 2).…”

“…Histological analysis of liver tissues using high fat/cholesterol/fructose diet-induced rodents revealed that hepatocytes highly express pyknotic nuclei, vacuolation, sinusoidal distension, necrosis, damaged endoplasmic reticuli, swollen and pleomorphic mitochondria, distorted intercellular spaces, irregular nuclear membranes, nuclear chromatin condensation, and cellular degeneration, suggesting that these diets contribute to liver damage. Hawthorn extracts improved these hepatic tissue injuries through antioxidant mechanisms, including the regulation of Nrf2 and ARE expression [30,36,37]. Remarkably, polyphenols obtained from hawthorn peels and flesh exerted a potent hepatoprotective action by efficiently ameliorating biochemical markers, hepatic lipid peroxidation, and liver tissue injury via the regulation of apoptosis-related proteins and antioxidant enzymes dysregulated by a high-fructose diets [38].…”

“…aronia, C. cuneata, and C. oxyacantha extracts also reduced the susceptibility of hepatocytes to steatosis induced by high-fat and high-atherogenic diets, mainly via mediating hepatic activity of HMG-CoA reductase, ACAT, and CYP7A1; hepatic cholesterol biosynthesis; and lipid excretion into bile acids [30,37,[68][69][70]. C. aronia and C. monogyna attenuated hepatic fat content by regulating hepatic GSH and TBARS and hepatic total thiol molecules, respectively, in Wistar rats [30,37]. Specifically, the antioxidant activity of 200 mg/kg C. aronia was more potent than that of 4 mg/kg of simvastatin [37] (Figure 2, Table 2).…”