Abstract
Hyperlipidaemia is a major risk factor for cardiovascular diseases, the leading cause of death globally. Celecoxib attenuated hypercholesterolaemia associated with CCl4-induced hepatic injury in rats without improving liver function in our previous study. This present study investigated the lipid lowering potential of celecoxib in normal rats fed with coconut oil subjected to five deep-frying episodes. Male Sprague Dawley rats were randomly assigned to groups (n = 6 rats/group) which received physiological saline (10 mL/kg), unheated coconut oil (UO, 10 mL/kg) or heated coconut oil (HO, 10 ml/kg) for 60 days. Groups that received HO were subsequently treated with either physiological saline, atorvastatin (25 mg/kg), celecoxib (5 mg/kg) or celecoxib (10 mg/kg) in the last fifteen days of the experiment. Rats were sacrificed 24 hours after last treatment and blood and tissue samples collected for analysis. HO consumption produced significant hyperlipidaemia and elevation in marker enzymes of hepatic function. Celecoxib ameliorated the hyperlipidaemia as shown by the significantly (P<0.05) lower total cholesterol, triglycerides, low and very low density lipoprotein in the celecoxib-treated rats when compared with HO-fed rats that received saline. Celecoxib also reduced (P<0.05) alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and liver weight of hyperlipidaemic rats. Similarly, hepatocellular damage with the hyperlipidaemia was significantly reversed by celecoxib. However, serum TNF-α and IL-6 did not change significantly between the various groups. Taken together, data from this study suggest that celecoxib may exert therapeutic benefit in hyperlipidaemia and its attendant consequences.
Highlights
Hyperlipidaemia, recognised as dyslipidaemia, describes the manifestation of different disorders of lipoprotein metabolism [1]
The celecoxib as well as atorvastatin did not alter the levels of the cytokines significantly (Fig 6)
We examined if the observed hypocholesterolaemic property of celecoxib in our previous study was unrelated to its hepatoprotective effect by evaluating its lipid lowering potential in rats fed with high fat and without chemically-mediated hepatic injury
Summary
Hyperlipidaemia, recognised as dyslipidaemia, describes the manifestation of different disorders of lipoprotein metabolism [1]. Bile acid sequestrants and nicotinic acid which constitute the major alternative modalities of treatment have some side effects [12] This notwithstanding, their control of lipid levels is far from satisfactory and calls for increased search for newer drugs with hypolipidaemic properties or repurposing of existing drugs for use in hyperlipidaemic conditions. Considering the huge cost, time, safety and legal challenges associated with discovery of newer drugs, repurposing of already existing drugs in clinical use for newer indications provides rapid alternative to ensure improved access to medicines with relatively minimal resources It is on this basis that we evaluate the FDA-approved selective COX-2 inhibitor, celecoxib, as a potential addition to the already existing pharmacotherapy for hyperlipidaemia in the current study
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