G Rajyalakshmi, A Reddy, V Rajesham
atorvastatin, hyperlipidemia, lipid lowering activity, simvastatin
G Rajyalakshmi, A Reddy, V Rajesham. A Comparative Antihyperlipidemic Activity Of Atorvastatin With Simvastatin In Rats. The Internet Journal of Pharmacology. 2008 Volume 6 Number 2.
The present study was aimed at comparing the pharmacodynamics of simvastatin (S) with atorvastatin in hyperlipidemic rats. The standard cholesterol diet was used to induce hyperlipidemia in Wister rats. The blood samples were collected from simvastatin and atorvastatin treated rats and analyzed for pharmacodynamics (lipid profiles) of using reported methods. Simvastatin produced a more significant change in lipid profiles than atorvastatin.
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.
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
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
On 8 th day, blood samples were withdrawn from the retro-orbital sinus into heparinized eppendorff tubes and plasma was obtained by immediate centrifugation of blood samples using Remi ultra cooling centrifuge at 3000 rpm for 5 minutes at room temperature. All samples were stored at 4C until analysis.
Plasma lipid levels include TC, TG and HDL-C were carried out 5 using respective diagnostic commercial kits and LDL-C in plasma was calculated as per Friedewald estimation 1112
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.
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).
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.
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.
(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: firstname.lastname@example.org email@example.com