Avaliação das toxicidades aguda e subaguda da Olea europaea L. e seu efeito no metabolismo de ratos diabéticos

Abstract

Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, insulin resistance and dyslipidemia. It is widely distributed worldwide, affecting millions of people and can lead to serious complications. Olive (Olea europaea L.) has important pharmacological activities, including antioxidant, anti-inflammatory and hypoglycemic. However, studies about its toxicity are still limited in the literature. Therefore, the aim of this study was to investigate the acute and subacute oral toxicities of the tincture of olive leaves (TOL) and evaluate the effect of TOL in metabolism of diabetic rats induced by high-fat diet and low dose of streptozotocin (STZ). In acute toxicity, a single dose of 2000 mg/kg of TOL was administered and observation was during 14 days, including behavior changes and signs of toxicity. In subacute study, TOL was administered for 28 days in the doses of 100, 200 and 400 mg/kg. Both treatments were by oral gavage in male and female rats and body weight was recorded. At the end of the experiment, blood was collected for biochemical and hematological analyses. The dose of 2000 mg /kg did not induce mortality or signs of toxicity. Animals exposed to repeated doses did not show abnormalities or hematological changes. At dose of 400 mg/kg, TOL increased levels of urea and reduced AST activity in males when compared to the different groups. Glucose levels decreased in males and females treated with TOL at different doses compared to controls. There was no significant change in body weight of animals in acute and subacute treatments. For the induction of experimental DM, animals were fed with a high-fat diet for 4 weeks and then was administered streptozotocin (35 mg/kg), via i.p., while the control group received regular diet and only citrate buffer via i.p. Rats with glucose levels above 200 mg/dL were considered diabetic. The animals were divided into 5 groups: Group I. negative control; Group II. diabetic treated with ethanol (51%); group III. diabetic treated with metformin (250 mg/kg) and groups IV and V. diabetic treated with TOL (200 mg/kg and 400 mg/kg, respectively). The administration was by oral gavage, daily, for 10 weeks. Hematologic and biochemical analyses were performed, as well as lipid peroxidation and antioxidant activity. The ALT activity was reduced in the groups treated with metformin and TOL (200 mg/kg) when compared to the control group and an increase in urea was observed in the group treated with TOL (200 mg/kg) compared to the control group. Treatment with TOL improved the levels of inflammatory markers (IL-6, IL-10, TNF-α and INF-γ) and adipokines (leptin, adiponectin and resistin) when compared to diabetic animals. There was no significant difference in MDA levels and no changes were observed in antioxidant activities. These results indicate that the exposure to a single or repeated doses did not induce toxicity and a potential anti-diabetic activity of tincture of olive leaves, but more studies are needed to validate its clinical effects and its safety for use in humans.