Influência in vivo de nutrientes sobre a citoxicidade e estabilidade genômica associadas à sobrecarga de açúcar.

Abstract

There is evidence that hyperglycemia is the main factor for the origin and progression of diabetes and it is associated with genotoxicity and cytotoxicity. Furthermore, there is evidence that some vitamins and minerals such as chromium (Cr), iron (Fe) and vitamin C can interfere in the risk of developing diabetes. The objective of this dissertation was to evaluate the effect of nutrients (Cr, Fe, vitamin C and invert sugar) on cytotoxicity, genomic stability and oxidative stress associated with hyperglycemia in vivo (Wistar rats). After 17 weeks of invert sugar intake in a concentration of 32%, the rats became obese and with prediabetes. At the same time, the rats presented a significant increase in abdominal fat, possibly caused by the increased caloric intake. Moreover, the rats presented an impaired glucose tolerance, assessed by Intraperitoneal Glucose Tolerance Testing (ipGTT). Primary DNA damage, assessed by the Comet assay,was increased in the blood, but not in the pancreas. It was not observed an increase in oxidative stress in the blood, measured by the protein carbonyls technique. Furthermore, no increase in chromosomal DNA damage was observed in bone marrow, as evaluated by the micronucleus test. Cr intake in the form of ClCr3 (58.4 mg/L) decreased blood glucose and improved glucose tolerance in the prediabetic rats. At the same time, Cr aided in decreasing the body mass index (BMI) and decreased then amount of peritoneal fat, when ingested alone or in combination with invert sugar. Despite the blood concentration of Cr be higher in animals supplemented with Cr, those animals receiving Cr in combination with invert sugar presented a depletion of this micronutrient in blood. In regards to the primary DNA damage, the groups that were supplemented with Cr had increased levels in the blood and lower levels in the pancreas in comparison to the control and invert sugar groups. Protein carbonylation assay or bone marrow micronucleus test showed no significant effects. The cotreatment with vitamin C, associated or not with invert sugar, contributed to a decrease in weight and peritoneal fat accumulation. Consequently, the group that received vitamin C and invert sugar promoted a decreased the BMI that resembled the control group in the end of the experiment. Vitamin C decreased the fasting glucose of both groups supplemented with Vitamin C and normalized glucose tolerance of group that received concomitant vitamin C and invert sugar treatment, matching the level of the control group. Fe overload decreased peritoneal fat and fasting glucose levels, but had no effect in obesity and glucose tolerance in the prediabetic rats. The Fe in blood concentrations did not differ between the groups, however, the Fe concentration in the pancreas decreased. The Fe group presented higher levels of DNA damage in blood, but not in pancreas. The Fe overload did not induce oxidative stress or mutagenicity. We conclude with this study that the prediabetes model induced by overdose of invert sugar was effective, because it simulated the metabolic characteristics of prediabetes in humans, involving changes in glucose metabolism without significantly affecting the functionality of pancreas or induced chromosomal damage to DNA. Cr improved glucose metabolism, however induced primary DNA damage in blood, but not in pancreas. However, Cr has not increased oxidative stress by protein carbonylation or chromosomal damage. The supplementation of vitamin C presented anti-obesogenic and hypoglycemic effects. Fe overload had no effect on glucose tolerance neither in obesity. Furthermore, the intake only influenced genotoxicity in the blood, measured by the comet assay.