Introduction

Hyperlipidemia is an elevation of one or more of the plasma lipids, including cholesterol, cholesterol esters, triglycerides and phospholipids ₁ , in which statins plays an important role for the treatment. Simvastatin ₂ and atorvastatin ₃ are lipid lowering agents, which act by inhibiting HMG-CoA reductase, which catalyses the conversion of HMG-CoA to mevalonate, an important rate-limiting step in cholesterol biosynthesis. They are used in the treatment of hyperlipidemia, atherosclerosis or cardiovascular complications like coronary heart disease. Among the available HMG-COA reductase inhibitors, Simvastatin and atorvastatin are the major two lipid lowering drugs to reduce the elevated lipid profiles in hyperlipidemic conditions. Statins, by inhibiting the synthesis of cholesterol, consistently reduce plasma low density lipoprotein (LDL)-cholesterol and total cholesterol levels ₄ (Davignon et al., 1992). However, their ability to reduce triglyceride concentrations depends on the baseline triglyceride levels and on the potency and efficacy of the statin used ₅₆₇ . The percentage reduction of lipid levels of these two drugs may relate to the differences in efficacy and duration of action. So far, few studies were conducted to compare the efficacy of these two drugs in animal models ₈ . In order to compare the efficacy or lipid lowering activity of these drugs in animals, we induced hyperlipidemia in rats successfully using the standard cholesterol diet (coconut oil/ cholesterol feed) ₉ .

Materials and methods

Atorvastatin pure drug (Dr. Reddy's Pharmaceutical Ltd, Hyderabad) and simvastatin pure drug (Orchid Pvt. ltd India) were obtained as a kind gift. Cholesterol kit (Enzymatic Method), HDL-C kit was procured from Qualigens Diagnostics, Mumbai. Triglycerides kit was obtained from E-Merck Limited, Mumbai, India.

Experimental animals

Male wistar albino adult rats weighing 200-230 g were selected and allowed to acclimatize to the environment for 7 days and supplied with a standard pellet diet and water ad libitum. The standard cholesterol diet along with butter (0.5 ml twice a day) was administered for 30 days to induce hyperlipidemia. At the end of one month blood was withdrawn from the tail vein to analyze ₁₀ for lipid profiles (Total Cholesterol (TC), triglycerides (TG), low density lipoproteins (LDL-C) and high density lipoproteins (HDL-C) levels) to confirm the induction of hyperlipidemia. Now the hyperlipidemic rats were divided into three groups of six each and treated with daily dose of atorvastatin or simvastatin for 7 days.

Group I: (HL) Control group of Hyperlipidemic rats received a dose of 1.5% carboxy methyl cellulose

Group II: (ST) Hyperlipidemic (HL) rats treated with simvastatin (80 mg/kg).

Group III: (AT) Hyperlipidemic (HL) rats treated with atorvastatin (80 mg/kg).

Collection of Blood samples

Biochemical analysis

Results

The effect of standard cholesterol diet on plasma lipid levels were shown in table 1 and lipid parameters of atorvastatin and simvastatin in hyperlipidemic rats were shown in table 2.

Figure 1

Table 1: Effect of standard cholesterol diet on plasma lipid levels (n = 25)

The plasma TC, TG, LDL-C levels and HDL-C levels were 0.98, 0.94, 1.54 and 0.7 fold respectively than normal rats after 1 month of standard cholesterol diet feed suggest the successful induction of hyperlipidemia in rats (table-1).

Figure 2

Table 2: Pharmacodynamic parameters of atorvastatin and Simvastatin day 8 (n = 6)

The plasma TC, TG and LDL-C levels were significantly reduced and HDL-C levels were increased by both statins. The decrease in plasma TC, TG and LDL-C levels was more (8%, 9.6% and 10.8%) in simvastatin treated group than atorvastain treated group. In contrast, the HDL-C levels were significantly more in AT treated group than ST group.

Discussion

Rats fed a standard cholesterol diet (coconut oil/cholesterol diet) develop hypercholesterolemia with increase in TG, LDL-C and HDL-C as shown in this and previous studies ₉. In cholesterol fed rats the increase in lipid levels are associated with diminished LDL receptor function and addition of oils containing saturated fatty acids causes a large down regulation of LDL receptor which led to higher cholesterol levels. Further, the amount of cholesterol returning to liver is increased and thus plasma HDL-C raises ₁₄ . The increase in plasma TG with this diet is due to the overproduction of VLDL ₁₅₁₆ . Treatment of standard cholesterol diet fed rats with AT and ST markedly decreased the plasma TC, TG and LDL-C levels relative to control animals.

The present results suggest that HMG-COA reductase inhibitors prevent the progression of hypercholesterolemia during treatment, though the plasma lipid levels remain much higher than in normolipidemic rats. This may due to the decreased HMG-COA reductase activity and LDL receptor function in chronically fed cholesterol rats ₁₇ . The decrease in plasma lipid levels was more in simvastatin treated group than atorvastain treated group. This may due to the ability of simvastatin to increase lipoprotein lipase activity in animals ₁₈₁₉ .

In conclusion, we have studied the comparative anti-hyperlipidemic activity of atorvastatin with simvastatin in rats. The significant finding was that, maximum percentage reduction of lipid levels were observed with simvastatin treatment than atorvastain.

Correspondence to

(Dr). Vollala Venkata Rajesham, M.Pharm, (PhD). Assistant Professor Srikrupa Institute of Pharmaceutical Sciences Velkatta, Medak dist, Andhra Pradesh, INDIA. Phone: 08457 210866 E-mail: anreddykuc@gmail.com vollala_rajesham@yahoo.co.in