Avaliação dos efeitos antiinflamatório, hipoglicemiante e hipolipemiante da lovastatina em roedores

Abstract

The anti-inflammatory, hypoglicemic and hypolipidemic effects of lovastatin were evaluated on animal models of carrageenan-induced peritonitis and paw edema and alloxan induced diabetes. Lovastatin reduced the paw edema, mL, induced by carrageenan at the doses of 2, 5 and 10 mg/kg during the period of measures: 2nd h (1,33 ± 0,12; 1,03 ± 0,19; 1,19 ± 0,21; respectively), 3rd h (2,30 ± 0,17; 1,76 ± 0,23; 1,93 ± 0,21) and 4th h (2,44 ± 0,12; 1,85 ± 0,21; 2,06 ± 0,35) when compared to control group (1,83 ± 0,21; 2,86 ± 0,24 e 3,26 ± 0,13). Indometacin used as reference drug also reduced the edema (0,96 ± 0,09; 1,28 ± 0,23 e 1,36 ± 0,17). Lovastatin reduced carrageenan-induced neutrophil migration at the doses of 2 mg/kg (16,0 ± 2,1 x 103/mm3), 5 mg/kg (16,1 ± 2,0 x 103/mm3) e 10 mg/kg (15,5 ± 2,3 x 103/mm3) when compared to control group (58,7 ± 10,5 x 103/mm3). Dexametasone used as reference drug showed similar results (14,3 ± 3,5 x 103/mm3). To evaluate the hypoglycemic and hypolipidemic effects a metabolic disorder was induced by injection of alloxan (40 mg/kg, i.v.) and different treatments schedules with lovastatin were used. On curative treatment, lovastatin reduced the alloxan induced-hyperglycemia, mg/dL on the fifth day of treatment at the doses of 2 mg/kg (reduction de 41,7%), 5 mg/ kg (43,3%), 10 mg/kg (45,3%) and 20 mg/kg (42,2%). Control group keep the level of hyperglycemia (334,1 ± 27,7; 335,5 ± 24,1). Similar results were found above triglycerides levels : 2 mg/kg (reduction of 70%), 5 mg/kg (55,4%), 10 mg/kg (47,6%) and 20 mg/kg (31%); Over cholesterol levels: 2 mg/kg (reduction of 33,6%), 5 mg/kg (36,7%), 10 mg/kg (35%) and 20 mg/kg (39,8%); Over AST levels: 2 mg/kg (reduction of 36%), 5 mg/kg (45%), 10 mg/kg (43%) and 20 mg/kg (37,8%). Over ALT levels only the dose of 20 mg/kg showed reduction (38,9%). A five-day preventive treatment with lovastatin (2 mg/kg) was carried out before the diabetes induction. Lovastatin prevent the hyperglycemia (170,7 ± 28,2 mg/dL) when compared to control (312,4 ± 22,0). The same happened to triglycerides 252,8 ± 46,7 e 461,3 ± 34,7, LOV e control, respectively) and cholesterol (112,4 ± 9,7 e 191,6 ± 18,9), however no difference between the groups were found when analyzing AST (34,4 ± 1,3 e 35,7 ± 2,1 UI/L) and ALT (44,2 ± 1,1 e 43,9 ± 1,2 UI/L). Also a subchronic treatment with lovastatin was undertaken. The parameters were evaluated at the day 0, day 5 and day 23. On glycemia lovastatin at the doses of 2 mg/kg (309,2 ± 30,5; 172,0 ± 38,0 e 176,7 ± 33,1) and 5 mg/kg (346,3 ± 21,5; 226,7 ± 25,8 e 125,8 ± 20,4) showed reduction when compared to control group (373,0 ± 47,5; 347,5 ± 26,2 e 338,6 ± 25,3). The same occured with triglycerides: 2 mg/kg (373,1 ± 97,6; 67,0 ± 48,4 e 179,8 ± 40,3), 5 mg/kg (606,9 ± 102,0; 195,2 ± 30,5 e 56,1 ± 10,0) and control (573,0 ± 27,2; 485,7 ± 54,2 e 459,7 ± 33,7); Cholesterol: 2 mg/kg (108,0 ± 8,4; 74,0 ± 5,8 e 73,4 ± 5,1), 5 mg/kg (117,5 ± 7,2; 75,9 ± 4,9 e 74,3 ± 6,4) and control (130,0 ± 6,3; 121,8 ± 4,9 e 116,4 ± 7,8). The treatment showed effect only over AST levels: 2 mg/kg (30,4 ± 2,3; 38,4 ± 3,4 e 29,4 ± 1,1), 5 mg/kg (38,7 ± 7,7; 46,7 ± 3,5 e 32,5 ± 5,5) and control (41,8 ± 1,8; 40,9 ± 6,3 e 69,6 ± 2,4). The association of lovastatin (2 mg/kg) and glybenclamide (5 mg/kg) did not enhance the effects of both drugs alone on glucose levels at the day 5 of treatment: LOV 2 (reduction of 64,5%), GLIB 5 (78%) e LOV + GLIB (77,6%). A similar effect was found when lovastatin was associated to metformin (50 mg/kg): LOV 2 (reduction of 64,5%), METF 50 (72%) e LOV + METF (75%). The results found show that the anti-inflammatory effect of lovastatin is an important parallel action, especially to prevent and treat vascular inflammatory disorders associated to atherosclerosis and diabetes. Besides that, the hypoglycemic effect of the drug seems to be independent of its hypolipidemic actions, suggesting an auxiliary action to treat diabetic patients.