Abstract

In the present study, the antioxidant activity of a methanol soluble fraction (MSF) from Cissus verticillata, used in Brazil and elsewhere as a hypoglycemic and antidiabetic medicinal plant, and tyramine (TYR), one of its main bioactive constituents, was assessed. For this, male Wistar rats were submitted to alloxan injection (40 mg/kg, i.v.) in order to induce a diabetic state and, 48 h later, glycemia was determined. Animals were distributed into groups: normal controls (NC); diabetic controls (DC); DC plus MSF; and DC plus TYR. Another group was treated with glibenclamide (GLI), used as a positive control. After 5-day treatments, animals were sacrificed for liver dissection, and determination of antioxidant markers such as thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), catalase and nitrite concentrations. The antioxidant effect was also evaluated on the pentobarbital-induced sleeping time, before and after CCl4 treatment. Under our experimental conditions, diabetic rats did not present any alteration in liver lipid peroxidation, before (DC) or after treatments with the MSF; TYR or GLI, as compared to normal controls (NC). Levels of GSH were significantly increased in 79% in DC, as related to NC, and the effects were partially reversed in diabetic rats, after MSF treatments at the higher dose. However, while similar effects were observed after TYR and GLI, both drugs brought values of GSH to normality. The DC group had increased liver catalase activity, as compared to NC, and these effects were partially reversed by MSF and almost completely by TYR and GLI. Significant increases were also detected in nitrite concentrations in livers of DC, as an index of free radical formation, and a large reduction was observed after MSF, TYR and GLI treatments of diabetic rats, as compared to NC. MSF and TYR also prevented prolongation of the pentobarbitalinduced sleeping time by CCl4, suggesting hepatoprotective and anti-oxidative effects. In conclusion, we showed that the antioxidant activity probably plays an important role in the antidiabetic effect of C. verticillata, and TYR is at least in part responsible for this property.

Highlights

  • Diabetes is associated with a significant oxidative stress, and this oxidative damage may contribute to several diabetic complications [1]

  • Since in previous studies we showed no alteration in serum hepatic transaminases from alloxan-induced diabetic rats after treatment with methanol soluble fraction (MSF) or TYR, we decided to investigate the alloxan-induced hepatotoxicity, in the absence and presence of

  • In Fig. (1), we present the effects of MSF, TYR and GLI on the formation of thiobarbituric acid reactive substances (TBARS), a parameter used to measure the aloxan-induced lipoperoxidation

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Summary

Introduction

Diabetes is associated with a significant oxidative stress, and this oxidative damage may contribute to several diabetic complications [1]. Reactive oxygen species are known to be an important part of the defense mechanisms against infection, but excessive generation of free radicals or unsaturated fatty acids have been implicated in the pathogenesis of vascular diseases [2]. Diabetic patients have an increased incidence of vascular diseases, and it has been shown that free radical activity is elevated during diabetes [3]. Free radicals seem to be responsible for the development of diabetic macroangiopathy as well as microangiopathy [4]. Previous studies [5, 6] demonstrated that increased freeradical reactions in patients with DM type II were responsible for the development of vascular changes. As a matter of fact, oxygen-derived free radicals have been suggested to

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