Effect of curcumin on triton WR 1339 induced hypercholesterolemia in mice

JB Majithiya, AN Parmar, R Balaraman 
 Pharmacy Department, Faculty of Technology and Engineering, Maharaja Sayajirao University of Baroda, Kalabhavan, Baroda - 390001, Gujarat, India

Correspondence Address:
J B Majithiya
Pharmacy Department, Faculty of Technology and Engineering, Maharaja Sayajirao University of Baroda, Kalabhavan, Baroda - 390001, Gujarat
India

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Sir,

Curcumin (diferuloylmethane), a major component of turmeric, is a yellow pigment obtained from rhizomes of Curcuma longa, is commonly used in Indian cuisine as a spice and food-coloring agent. Curcumin and its analogues have a variety of physiological and pharmacological activities such as antioxidant, antiinflammatory, and anticarcinogenic properties.[1] The ability of curcumin to inhibit LDL oxidation and hypocholesterolemic effect in rabbits has been studied. Administration of curcumin to streptozotocin diabetic rats improves lipid profile. The ability of curcumin to decrease serum cholesterol, triglycerides and lipids has been studied extensively in various animal models by different authors.[1],[3] But the effect of curcumin on hyperlipidemia induced by triton WR 1339 (Tyloxapol: a nonionic detergent, oxyethylated tertiary octyl phenol formaldehyde polymer) has not yet been studied. In this model to study the hypolipidemic drugs, triton WR 1339 is administered i.v. or i.p. in rodents to produce hypercholesterolemia by accelerating hepatic cholesterol synthesis[5] while in other models, hyperlipidemia is produced by feeding high cholesterol or high fat diet. Moreover Paoletti[4] suggested the use of triton WR 1339 induced hyperlipidaemia as an important approach to screen the action of hypolipidemic drugs. Hence in the present study, the effect of curcumin on serum triglycerides and total cholesterol was studied in triton WR 1339 induced hyperlipidemic mice.

The experiments and protocols described in present report were approved by the Institutional Animal Ethics Committee and are in accordance with guidance of Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA). The study was carried out in in-bred, male, Swiss albino mice (25 ± 4 g). All animals were housed in group of 6 and maintained under standardized condition (12/12 h light/dark cycle, 24° C) with free access to pellet food (CHAKKAN diet, Pranav Agro Pvt. Ltd., India) and water. triton WR 1399 (Tyloxapol) was obtained from Sigma, St. Louis, MO, USA. Curcumin was obtained as a gift sample from Cherrain Chemicals Ltd., India. Curcumin was orally administered in 0.5% sodium carboxy methyl cellulose suspension.

Hyperlipidemia was induced by single intravenous injection of 200 mg/kg of triton WR 1339 in normal saline. Control animals were injected with normal saline

The animals were divided into following groups.

ControlTriton controlTriton treated + curcumin 100 mg/kgTriton treated + curcumin 200 mg/kgTriton treated + curcumin 400 mg/kg

Curcumin (100, 200 and 400 mg/kg) was orally administered, immediately as well as 24 h after triton injection. Mice were not fed but had free access to water during the experiment period (44 h). Forty four hours after triton injection, blood was collected from anaesthetized mice by cardiac puncture. Serum cholesterol and triglycerides were estimated using commercially available kits (SPAN Diagnostics Pvt. Ltd.)

The results are expressed as mean ± SEM. The difference between groups was analyzed by one-way analysis of variance (ANOVA) followed by Dennett's test with 5% level of significance (Pet al[2] have previously shown the hypocholesterolemic effect of curcumin in human volunteers. Curcumin is reported to have hypolipidemic effect in cholesterol fed rabbits, hypercholesterolemic rats and streptozotocin diabetic rats. This could be due to an increase in HDL cholesterol[3], indicating that curcumin may be mobilizing cholesterol from extra hepatic tissues to the liver where it is catabolised. Curcumin is reported to activate the rate limiting step in cholesterol catabolism, that is, cholesterol 7- -hydroxylase thereby stimulating the conversion of cholesterol to bile acid, an important pathway in the degradation of cholesterol.[7] The present study shows that the reduction in total cholesterol and triglycerides by curcumin is not attributed to a decrease in absorption of lipids from diet, as lipids (diet) were not administered during the study. Hepatic cholesterol synthesis is accelerated by triton WR 1339. Moreover, triton physically alters very low density lipoproteins rendering them refractive to the action of lipolytic enzymes of blood and tissues, preventing or delaying their removal from blood.[6] Hence the hypolipidemic effect of curcumin administration could be due to an increased catabolism of cholesterol into bile acids.

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