Simvastatin and vitamin E effects on cardiac and hepatic oxidative stress in rats fed on high fat diet

Abstract

High fat diet (HFD) is a common cause of metabolic syndrome and type 2 diabetes mellitus. Published data showed that HFD and subsequent dyslipidemia are major triggers for oxidative stress. Forty-eight male Sprague-Dawley rats, weighing 170-200 g, were divided into six groups: control, control with vitamin E (100 mg/kg/day, i.p.), control with simvastatin (SIM) (10 mg/kg of body weight/day), HFD, HFD with vitamin E, and HFD with SIM. Standard and high cholesterol diets were given for 15 weeks and SIM and vitamin E were added in the last 4 weeks. In all rats, serum vitamin E, total cholesterol (TC), triglycerides (TG), low (LDL) and high (HDL) density lipoproteins, alanine (ALT) and aspartate (AST) transaminases, alkaline phosphatase (ALP), and gamma glutamyl transpeptidase (GGT) as well as cardiac and hepatic thiobarbituric acid-reactive substances (TBARS) and antioxidants (reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT)) were measured. Also, electrocardiogram (ECG) was recorded. HFD significantly increased QTc interval, heart rate (HR), serum TC, TG, LDL, ALT, AST, ALP, GGT, liver TG, and cardiac and hepatic TBARS but decreased antioxidants and HDL, while SIM decreased HR, liver TG, serum TC, TG, and LDL and increased HDL in HFD rats. Vitamin E had no effect. Moreover, SIM and vitamin E decreased QTc interval, serum ALT, AST, ALP, GGT, and cardiac and hepatic TBARS and increased antioxidants in HFD rats. Histopathological observations confirm the biochemical parameters. SIM and vitamin E slow progression of hypercholesterolemia-induced oxidative stress in liver and heart and improve their functions.

Liver X Receptor Agonist TO901317 Attenuates Paraquat-Induced Acute Lung Injury through Inhibition of NF-κB and JNK/p38 MAPK Signal Pathways

“…Hypercholesterolemia is well known as a risk factor of oxidative stress which leads to increase of excess formation of ROS [40, 41] and diminished endogenous antioxidant capacity [42, 43]. Since Wang et al [44] reported that the plasma levels of cholesterol significantly increased in PQ poisoned patients in comparison to healthy volunteers, we hypothesize that PQ toxicity may also be associated with the changes of cholesterol metabolism.…”

Functions of Coenzyme Q10 Supplementation on Liver Enzymes, Markers of Systemic Inflammation, and Adipokines in Patients Affected by Nonalcoholic Fatty Liver Disease: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial

“…In contrast to GGT, they did not find a relationship between CoQ10 status and serum AST activity [34]. Moreover, our search found many animal studies that reported the beneficial effects of CoQ10 administration on serum liver enzymes in rats [20,[36][37][38][39][40].…”

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

“…The discrepancies could be attributed to the assessment methods used; basic histological staining in theirs compared to transmission electron microscopy methods in ours. Furthermore, simvastatin was also found to reduce the levels of blood cholesterol and triacylglycerol (Wang et al, 2013), and liver TBARS (Ozansoy 2001), however it failed to increase the antioxidants GSH, glutathione-S-transferase, and glutathione peroxidase in liver tissue homogenates obtained from rats fed on HFD and from aged rats (Abbas & Sakr, 2013, Helmy, 2012. These findings are in total agreement with our data reported here on the effect of simvastatin that showed a reduction in blood lipids, TBARS, but no significant GSH increase with simvastatin (Table I).…”