Hypolipidemic effects of nimesulide and celecoxib in experimentally induced hypercholesterolemia in rabbits

Abstract

IntroductionAtherosclerosis, leading to myocardial infarction and stroke, is one of the most important causes of death due to cardiovascular diseases (1). The association of hypercholesterolemia with atherosclerosis is well known (2). Studies suggest that elevated lipoproteins in blood, and especially low-density lipoproteins (LDL), play an important role in the pathogenesis of atherosclerosis as indicated by their accumulation in atherosclerotic lesions (3,4). Therefore, reduction of LDL-cholesterol is an important target for the prevention and treatment of atherosclerosis.Nonsteroidal antiinflammatory drugs (NSAIDs) are used clinically as antiinflammatory, antipyretic, and antirheumatic agents (5). They exert their effect by inhibiting cyclooxygenase (COX) activity with subsequent inhibition of the formation of prostaglandins, prostacyclins, and thromboxanes (6). Several studies have shown that indomethacin or ibuprofen reduces the plasma cholesterol levels in humans or laboratory animals (7,8). Indomethacin can lower the cholesterol content of atherosclerotic blood vessels and liver in monkeys and rabbits (9), and when combined with inhibitors of angiotensin converting enzymes, indomethacin lowers blood cholesterol levels in humans (8). NSAIDs, especially flufenamic acid and indomethacin, increase LDL binding, cell association, and degradation by increasing the expression of the mRNA of the LDL receptor protein in HepG2 cells (5). Celecoxib, a selective COX-2 inhibitor, lowers plasma cholesterol during carbon tetrachlorideassociated hepatotoxicity in rats (10). Therefore, these studies suggest that COX inhibition may be useful in treating hypercholesterolemia.Reduction in the LDL levels can be achieved by the use of statins, which are the currently employed widely for the Background/aim: Hypercholesterolemia plays an important role in the development of atherosclerotic disease, which is one of the leading causes of mortality in the world. Previous studies showed that cyclooxygenase (COX) inhibitors could be used in treating hypercholesterolemia. The present study was designed to test whether COX-2 inhibition can improve lipid profiles in hypercholesterolemia.Materials and methods: Rabbits were fed a high-cholesterol diet to produce hypercholesterolemia. The role of COX-2 was evaluated using celecoxib and nimesulide. Rabbits were divided into 4 groups: the first with normal healthy rabbits, second with high-cholesterol diet and pretreatment with saline, third with high-cholesterol diet and pretreatment with celecoxib, and fourth with high-cholesterol diet and pretreatment with nimesulide. Total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglyceride levels were measured at 2-week intervals in all the groups.Results: Results show significantly high levels of serum cholesterol, LDL, and triglyceride but low levels of HDL in hypercholesterolemic rabbits pretreated with saline. Rabbits pretreated with nimesulide and celecoxib showed improvement compared to the saline-treated gro...

Dietary Cholesterol and the Lack of Evidence in Cardiovascular Disease

“…Cardiovascular disease (CVD) is a leading cause of death in the US with approximately one in every four deaths occurring from heart diseases [ 1 ]. According to the CDC, 610,000 individuals die from CVD in the US [ 2 ]. The landmark of CVD is atherosclerosis, which is a chronic inflammatory condition instigated by deposition of cholesterol and fibrous tissues in the arterial walls which build up and eventually lead to narrowing and thickening or blocking of the arterial lumen.…”

Celecoxib exhibits therapeutic potential in experimental model of hyperlipidaemia

“…All these markers are known to be up-regulated in inflammatory conditions and other disorders which have inflammatory subsidiaries. Some NSAIDs such as ibuprofen have been shown to lower plasma cholesterol levels and reduce the progression of atherosclerosis [ 15 – 17 ] while others like indomethacin lower cholesterol content in liver and atherosclerotic blood vessels [ 18 , 19 ].…”

“…There has been a general assumption that COX-2 inhibitors may be beneficial in atherosclerosis, liver disease and hypercholesterolaemia since pathogenesis of these diseases is closely linked with prostaglandins [ 15 ] and since upregulation of COX-2 expression has also been demonstrated in hyperlipidaemia [ 26 ]. In our previous study, celecoxib was observed to significantly attenuate hypercholesterolemia and lipid peroxidation associated with liver injury during carbon-tetrachloride–associated hepatotoxicity in rats [ 27 ].…”

Hypercholesterolemia and hypertriglyceridemia as biochemical markers of disease in companion rabbits

“…Decreased HDL cholesterol and increased serum amyloid A (SAA) and TG concentrations have been demonstrated in rabbits in response to inflammatory stimuli . Cyclooxygenase inhibitors, which reduce prostaglandin synthesis in many inflammatory pathways, decreased serum TG and CHOL levels in rabbits with experimental diet‐induced hypercholesterolemia, although the mechanism was not determined . Pet rabbits can develop various infectious and inflammatory conditions such as bacterial abscesses, gastrointestinal dysbiosis, and protozoal infections that could be useful in evaluating the relationship between lipids and inflammation in this species.…”