COMPARATIVE STUDY OF EFFECT OF SWERTIA CHIRATA LEAF EXTRACT ON INDINAVIR TREATED RATS
Background: Indinavir is widely used for the treatment of human immunodeficiency virus (HIV) infection. It is known to cause hyperglycemia or insulin resistance and hyperlipidemia.
Aim and Objectives: To study the effect of Swertia chirata leaf extract with metformin and pioglitazone on indinavir treated rats.
Methods: Swiss albino rats were divided into five Groups of six animals each. All the groups (except control) were treated with indinavir 216 mg/kg (oral) for 15 days. Group I (control) received normal saline (oral) from day 8 to day 15, Group II received indinavir 216 mg/kg (oral), Group III received S. chirata plant extract 500 mg/kg (oral) from day 8 to day 15, Group IV received pioglitazone 4 mg/kg (oral) from day 8 to day 15, and Group V received metformin 36 mg/kg (oral) from day 8 to day 15. The biochemical parameters such as serum glucose, insulin, and lipid levels were measured on day 15. Results were analyzed using one-way analysis of variance followed by Bonferroni's multiple comparison test.
Results: Indinavir (216 mg/kg) treated rats showed a significant (p<0.05) increase in glucose and insulin levels and also altered lipid levels. This indicates indinavir produces diabetic-like state in rats. S. chirata extract (500 mg/kg) decreases glucose and insulin levels and also improves lipid levels the effect is almost similar to metformin and pioglitazone.
Conclusion: Indinavir causes elevated glucose, insulin and lipid levels, so care must be taken while prescribing indinavir for HIV patients. Treatment with S. chirata extract improved the altered glucose, insulin, and lipid profile in indinavir treated rats.
Key words: Indinavir, Insulin resistance, Diabetes dyslipidemia, Glucose intolerance.
2. H.L.Sharma, K.K.Sharma. HIV and antiretroviral drugs, principles of Pharmacology, 1st edition, Paras Medical Publisher, New Delhi: 2007;809-820.
3. Dube MP, Johnson DL, Currier JS, Leedom JM. Protease inhibitor associated Hyperglycaemia. Lancet 1997; 350:713â€“714.
4. Noor MA, Lo JC, Mulligan K, Schwarz J-M, Halvorsen R, Schambelan M, et al. Metabolic effects of indinavir in healthy HIV-seronegative men. AIDS. 2001; 15(7): 11-18
5. Schwarz JM, Lee GA, Park S, Noor MA, Lee J, Wen M, et al. Indinavir increases glucose production in healthy HIV-negative men. AIDS. 2004 ; 18(13):1852-4
6. D Nolan. Metabolic complications associated with HIV Protease inhibitor therapy. Drugs. 2003; 63(23): 2555-2574
7. Dr.Michael P.Dube. Disorders of glucose metabolism in patients infected with human immunodeficiency virus. Oxford Journals Medicine Clinical Infectious Diseases. 31(6): 1467-1475
8. Christos Mantzoroz, Scott Hammer, Mathew Samore. Effects of protease inhibitors on Hyperglycemia,Hyperlipidemia, and Lipodystrophy. Arch Intern Med. 2000;160: 2050-2056
9. SK Mastan ,K Eswar Kumar, Relative potency of protease inhibitors on glucose-insulin homeostasis, hemoglobin and glycosylated hemoglobin in normal rats. Der Pharmacia Letter. 2009; 1(1): 108-116
10. Brown TT, Cole SR, Li X, Kingsley LA, Palella FJ, Riddler SA, et al. Antiretroviral therapy and the prevalence and incidence of diabetes mellitus in the multicenter AIDS cohort study. Arch Intern Med. 2005; 165(10):1179â€“84.
11. Palella FJ, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. New Eng Journal Med.1998; 338: 853-60.
12. Gren ML. Evaluation and management of dyslipidemia in patients with HIV infection. J Gen Intern Med 2002; 17(10):717-810.
13. Justman JE, Benning L, Danoff A, et al. Protease Inhibitor use and the incidence of diabetes mellitus in a large cohort of HIV-infected women. J Acquir Immune Defic Syndr. 2003; 32:298-302.
14. Gawly HW, Tawfik MK, Rashwan ME, Baruzaig AS, et al. The effect of pioglitazone on the liver of streptozotocin-induced diabetic albino Wistar rats. European Review for Medical and Pharmacological Sciences. 2009;13(6):443-51.
15. Juei-Tang Cheng, Ching-Chiu Huang, I-Min Liu, Thing-Fong Tzeng andChih Jen Chang. Novel Mechanism for Plasma Glucoseâ€“Lowering Action of Metformin in Streptozotocin-Induced Diabetic Rats, Diabetes.2006; 55(3):819-825.
16. Grunfeld. Insulin Resistance in HIV Infection: drugs, Host responses or restoration to health, International AIDS Societyâ€“USA. 2008; 16 (2):89-94.
17. sanjay karla, bharti karla, navneet agrawal ,AG unnikrishnan,Understanding of diabetes in patients with HIV/AIDS, Diabetology and metablic syndrome.2011;3:1-7
18. Ismail wiw, Pillay TS, Insulin resistance induced by antiretroviral drugs: Current understanding of molecular mechanisms, JEMDSA. 2009; 14(3):129-132.
19. Alessandra vigano, Paolo brambilla, giulia pattarino, sara stucchi, silvia fasm, Long term evaluation of glucose homeostasis in cohort of HAART-Treated HIV- Infected children, Clin drug invest. 2009;29(2):101-109
20. J.Gomez vera, A.de.alarcon.M.E.Jimenez, D.Acasta, D.Prados and P.Viciana, Hyperglycemia associated with protease inhibitors in HIV-1-infected patients, clinical microbiology and infectious diseases. 2000;6(7): 389-393
21. H.B.Maurice, Molecular interaction between insulin receptor and protease inhibitors that leads to diabetes in people taking ARVS, TAJONAS. 2010;1(1): 51-56
22. Paul w. Hruz, Haruhiko murata, Indinavir Induces Acute and Reversible Peripheral Insulin Resistance in Rats. DIABETES.2002; 51:937-943
23. Young Hee Choi, Myung Gull Lee, Inchul Lee, Effects of Diabetes Mellitus Induced by Alloxan on the Pharmacokinetics of Metformin in Rats: Restoration of Pharmacokinetic Parameters to the Control State by Insulin Treatment, J Pharm Pharmaceut Sciences.2008;11(1): 88-103.
24. Sekar BC, Mukherjee B, Chakravarti RB, et al. Effect of different fractions of Swertia chirata on blood sugar level of albino rats. Journal Etnopharmacology.1987; 21: 175-81.
25. Kavitha.K.N, Dattari.A.N, Experimental evaluation of antidiabetic activity ofswertia chirata aquous extract, Journal of public health and medical research, 2013;1(2):71-75
26. Rafatullah.S, Mass J.S, Tariq M, Aleyaha M.A, Ageel A.M, Protective effect of swertia chirata against indomethacin and other ulcerogenic agents induced gastric ulcers, Experimental clinical research. 1993;19(2):69-73
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