Experimental diabetes treated with ficus carica extract: effect on oxidative stress parameters

Outline

• Abstract
• Keywords
• Introduction
• Materials and Methods
• Animals
• Fig Leaf Processing
• Extract Administration
• Blood Processing
• Biochemical Analyses
• Statistical Analysis
• Results
• Discussion
• References

Discussion

Our results show that aqueous (basic) and organic (chloroform) extracts of Ficus carica leaves have similar effects in reducing hyperglycaemia in diabetic rats, whereas the chloroform extract has a greater effect in reducing fatty acid levels. As of now, we know neither the mechanism of action nor the chemical composition of the extracts.

There is evidence that oxidative stress plays a major role in the aetiology of diabetic complications [18]. Several studies have shown an increase in lipoperoxidation products in diabetic patients [19], while others have not shown any such differences [20], or an increase only in diabetic patients with complications [21] or who were poorly controlled [22]. Balashova et al. [23] reported that catalase activity rises by approximately 50% in insulin-dependent patients with angiopathies. The antioxidant status is fairly poor in both glucose intolerance and non-insulin-dependent diabetes, and it is possible that antioxidant therapy mitigates or retards the progress of glucose intolerance [24]. In studies on non insulin-dependent diabetics who underwent insulin therapy for three days, there was a slight decline in their high levels of malondialdehyde and a rise in the levels of vitamin E, but there were no modifications in the activities of catalase or superoxide dismutase [25].

In our present work, the erythrocyte catalase activity in diabetic animals was significantly greater than that of the control group. This indicates a greater activation of the oxidative defences, in agreement with the suggestion of Ohrvall et al. [26].

One way of comparing different individuals is to consider the ratio between the erythrocyte catalase activity and the haemoglobin content. Our data regarding this ratio still indicate a greater enzyme activity in the diabetic animals relative to the normal controls. On considering, however, the values for the animals who received the basic and the chloroform fractions, we found a decline with respect to the values for the diabetic animals, there being no such difference relative to the normal animals. It is not easy to draw clear conclusions from these data: given the erythrocyte half-life, we cannot explain how a single intraperitoneal injection of a Ficus carica extract can change either the total erythrocyte catalase content or its activity, although, in the absence of other data, the latter seems the more plausible cause.

There are many free radical generating mechanisms, but their presence is translated into a series of lipid peroxidation products which include malondialdehyde, a protein-modifying agent [27]. This compound is most commonly used as the marker of the degree of lipoperoxidation. Despite the importance of oxidative stress, its in vivo determination has not led to conclusive results: the interpretation of the relationship between measurements of the products of lipoperoxidation and diabetes has led to certain contradictions in the literature [9]. There are also conflicting results concerning alpha-tocopherol and diabetes, since one may find articles describing it as increased, unchanged, or decreased [28]. A possible explanation of the different conclusions reached in different studies may be that not only is there a rise in free radicals in diabetes, but that there is also an enhancement of the organism’s vitamin and enzyme defences.

Some studies detected a greater level of malondialdehyde in diabetic patients who also presented arteriosclerotic symptoms than in those without such symptoms. It may be that lipoperoxidation occurs in such places as the atheromal plaque, and only with time and the progress of the lesions do the molecules of malondialdehyde diffuse into the blood plasma in amounts that are sufficient for their detection [29]. We found no variation in plasma or erythrocyte malondialdehyde levels between the four groups of rats studied (controls, diabetic, diabetic treated with basic fraction, and diabetic treated with chloroform fraction). In a day-by-day study of a numerous group of people, it was found that the great variations in MDA call into question the usefulness of this parameter as an indicator of lipoperoxidation [30].

Some studies have shown the control of diabetes to improve with the administration of high doses of vitamin E to patients, since it protects the fatty acids of the cell membrane and thereby preserves their functions with respect to insulin [31]. Daily administration of 600 mg vitamin E for 3 months to a group of non-insulin-dependent diabetic patients decreased in basal insulin levels [32]. Insulin Dependent patients had a concentration of total plasma vitamin E similar to that of controls, but the ratio of vitamin E to lipids was lower than in normal subjects [33]. The absolute levels of vitamin A are significantly less in insulin dependent patients than in normal subjects [33].

In studies with well-controlled non-insulin-dependent patients, both vitamin A and vitamin E levels are significantly higher than in healthy subjects taken as controls, and this is also the case for diabetic patients with hyperlipidaemia.

Our results show that diabetic animals present a concentration of vitamin E that is far greater than that in normal animals. We also observed a fall in vitamin E levels relative to the diabetic group’s values in the animals who received the Ficus carica extracts. However, when we considered the ratio of vitamin E to triglycerides as a measure of the concentration of the liposoluble vitamin in its natural medium, we observed the greatest values of the ratio in normal animals; the ratio was unmodified in animals that received the respective fraction. When we normalized vitamin E levels to those of polyunsaturated fatty acids and especially of linoleic acid, which the vitamin protects from peroxidation, the values for animals that received the extracts were similar to that of the controls. The levels of total vitamin A showed no differences between normal and diabetic animals. When we considered the vitamin A/triglyceride ratio, we observed lower levels in diabetic than in normal rats and with the administration of either Ficus carica extract to diabetic animals, the ratio increased. The ratio of vitamin A to PUFA levels was unchanged in diabetic animals who received the extracts. The vitamin A/linoleic acid ratio, however, was significantly raised relative to the untreated diabetic rats.

We conclude that the administration of the basic and chloroform extracts of Ficus carica affects the oxidative stress in diabetes, with particular significance regarding the vitamin E/C18:2 ratio when the chloroform fraction is administered, and the vitamin A/C18:2 ratio with the basic fraction.