Assessment of the Prophylactic Role of Aspirin and/or Clopidogrel on Experimentally Induced Acute Myocardial Infarction in Hypercholesterolemic Rats

Abstract

IntroductionHyperlipidemia is a risk factor for cardiovascular diseases such as acute infarction. Inflammation and platelet activation are critical phenomena in acute myocardial infarction (AMI).AimThe aim of the study was to assess potential protective effects of aspirin and/or clopidogrel on AMI in hypercholesterolemic rats.MethodsForty adult male Wistar rats were divided into five groups (eight rats in each). Group I included normal healthy rats. The other 32 rats were subjected to induction of hypercholesterolemia by high-fat diet for 3 weeks, followed by induction of AMI by subcutaneous injections of isoproterenol (85 mg/kg/day, for 2 days). Rats were divided into the following groups: group II, rats with induced hypercholesterolemia and AMI; group III, hypercholesterolemic rats that received aspirin 30 mg/kg/day orally for 7 days before induction of AMI; group IV, hypercholesterolemic rats that received clopidogrel 10 mg/kg/day orally for 7 days before induction of AMI; and group V, hypercholesterolemic rats treated with both aspirin and clopidogrel in the same doses for 7 days before induction of AMI. Serum levels of pentraxin 3 (PTX3), transforming growth factor-β1 (TGF-β1), creatine kinase (CK), lactate dehydrogenase (LDH), total cholesterol and triglycerides were estimated in all rats.ResultsIsoproterenol-induced AMI in hypercholesterolemic rats was associated with an increase in serum levels of PTX3, TGF-β1, CK and LDH. Aspirin and/or clopidogrel pretreatment for 1 week led to a reduction of their levels as compared with non-treated rats. However, the reduction caused by combination of aspirin and clopidogrel was more than that caused by each drug separately.ConclusionCombination of aspirin and clopidogrel could be a therapeutic option for hypercholesterolemic patients to attenuate the complex vascular inflammatory process which is a key step in the setting of AMI.

Hypolipidemic, antioxidant and anti-atherosclerogenic effect of aqueous extract leaves of Cassia. occidentalis Linn (Caesalpiniaceae) in diet-induced hypercholesterolemic rats

“…This reduction of cholesterol is found on the level of the TC, the LDL-c and Triglycerides. These results are similar with those of several works completed with other plant extracts, such as the aqueous extract of Dunaliella salina [27] and the ethanolic extract of Crataegus pinnatifida [28], in rats subjected to a feeding regime enriched with lipids. Considering that abnormal lipid profiles constituting the hallmark of HC-induced metabolic syndrome were also prevented in the liver by the extract concomitantly with a marked increase in total cholesterol excreted, we hypothesized that hypolipidemic activity of the extract may be mediated by reducing or inhibiting intestinal cholesterol absorption and increasing reverse cholesterol transport, as observed with agents inducing comparable hypolipidemic effects together with antioxidant effects such as Ezetimibe [29, 30] and bile acid sequestering cholestyramine [22, 31].…”

Drug-induced mitochondrial toxicity: Risks of developing glucose handling impairments

“…However, therapeutic doses administered in humans did not exhibit any mitochondrial respiratory chain impairment (113). Clopidogrel reactive metabolites depleted cellular glutathione content in HepG2 cells and primary human hepatocytes leading to the accumulation of ROS and mitochondrial impairment (65,113). A study conducted by Maseneni et al et al (113) in human lymphocytes and neutrophil granulocytes observed a reduction in inner mitochondrial membrane potential, induced release of cytochrome c, and enhanced production of ROS in the presence of clopidogrel.…”

“…However, therapeutic doses administered in humans did not exhibit any mitochondrial respiratory chain impairment ( 113 ). Clopidogrel reactive metabolites depleted cellular glutathione content in HepG2 cells and primary human hepatocytes leading to the accumulation of ROS and mitochondrial impairment ( 65 , 113 ). A study conducted by Maseneni et al.…”

The Multiple Pharmacologic Functions and Mechanisms of Action of Guizhi Fuling Formulation

“…High cholesterol concentrations in serum have key roles in the progression of hypercholesterolemia and nonalcoholic fatty liver disease (NAFLD), which are critical risk factors for many cardiovascular diseases, including atherosclerosis, hypertension, and myocardial infarction [82]. One study reported that GZFL improved atherosclerosis by downregulating the levels of triglyceride (TG), alkaline phosphatase (ALP), alanine aminotransferase (ALT), and ICAM-1 (a marker of activation of the endothelial cell) in the serum, as well ICAM-1 expression in the aorta, of rats fed a highcholesterol diet [83].…”