Tese
Efeito protetor da N-acetilcisteína sobre o estresse oxidativo causado pela administração crônica de aspartame em ratos
Fecha
2015-03-12Autor
Finamor, Isabela Andres
Institución
Resumen
This thesis evaluated the N-acetylcysteine effects (150 mg/kg, intraperitoneal) on the
biochemical and oxidative changes caused by the daily oral consumption of aspartame at 40
mg/kg for six weeks by rats. For this purpose, were performed two experiments, in both the
animals were divided in four groups: Control – received both aspartame and Nacetylcysteine
vehicles; NAC – received aspartame vehicle, and N-acetylcysteine; ASP –
received aspartame, and N-acetylcysteine vehicle; ASP-NAC – received both aspartame and
N-acetylcysteine. The aspartame was administrated for six weeks; whereas the Nacetylcysteine
was injected only in the fifth and sixth week. After it, the animals were
anesthetized, their blood was removed, the serum was separated; and then, the rats were
euthanized by exsanguination. In the first experiment, the serum was used for the
measurement of glucose levels and also biomarkers of kidney and liver damage; the whole
brain, liver and kidney were removed for the analysis of the oxidative stress parameters. As
the results, in general, aspartame caused hyperglycemia and oxidative stress in the whole
brain, and hepatic and renal tissues. N-acetylcysteine treatment protected all these tissues
against the oxidative damage (lipid peroxidation and protein carbonylation), in especial, by
promoting the reduced glutathione (GSH) synthesis, inducing the enzymes related to its
metabolism (glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione Stransferase),
and elevating the ascorbic acid levels and total reactive antioxidant potential. In
the second experiment, the serum was utilized for the determination of glucose content and
lipid profile; the liver was removed for glucose measurement; and the whole brain was
separated in the following structures: cerebral cortex, cerebellum, brainstem, and
hypothalamus; in which was held the research of the oxidative stress biomarkers. The
aspartame consumption caused an elevated glucose production in the liver, hyperglycemia,
hypertriglyceridemia, hypercholesterolemia; and oxidative stress in all the brain regions.
Although N-acetylcysteine treatment did not reduce neither the synthesis of liver glucose nor
the hyperglycemia, it normalized the triglycerides and high-density lipoprotein cholesterol in
the serum. This antioxidative treatment also protected all the brain regions against the lipid
peroxidation, increased GSH levels and induced its associated enzymes (GPx and GR),
triggering different defensive responses according each brain region. Therefore, the data of
this thesis suggest that N-acetylcysteine attenuates the oxidative damage generated by the
intake of this artificial sweetener. More studies were needed to elucidate the signaling
pathways involved in this process; as well as to determine the aspartame metabolites levels
(phenylalanine, aspartate and methanol) found in the rat plasma and brain.