• English
  • Português

Data of Thesis


Author: Luana Jotha Mattos

Title: Sublethal effects of microcystin (cyanotoxin) on biochemical, physiological and stereological aspects in murine models.

Year: 2011.                                         Full text (in Portuguese)


Microcystins (MCYST) are the cyanotoxins with more reports of human poisoning, but the sublethal dose effects of these toxins are poorly studied. Therefore, the aim of this study was to contribute to knowledge about the effects of intoxication by MCYST-LR (sublethal dose) in mammals, investigating biochemical and physiological changes, processes of accumulation and detoxification, as well as investigate the functional and tissue damage in the exposed animals. We used mice and rats as experimental models. The mice were exposed to MCYST-LR i.p. with single sublethal dose of 45 mg MCYST-LR / kg bw. Their organs were collected at 2, 8, 24, 48 or 96 h. The rats were injected (IP) with single sublethal dose of 55 mg MCYST-LR / kg BW and their organs were collected after 24 h. In all experiments, control animals received saline solution. In mice, we could detect oxidative damage in the liver, particularly in 8 h after exposure, justified by the increased activity of SOD (superoxide dismutase), decreased activity of CAT (catalase) and GPx (glutathione peroxidase) and increased lipid peroxidation. Inhibition of protein phosphatase (PP) occurred during the experimental period. Analysis of nitric oxide and myeloperoxidase were not considered as good biomarkers of inflammation. The activity of GST (glutathione S-transferase) increased at early sample days, indicating detoxification. The biomarkers of liver injury were detected in high concentrations in the serum of animals exposed during the sample period. Stereological analysis indicated an initial moment of intoxication, justified by the increase of steatosis, and a later moment of intoxication, justified by the increase of inflammation and hepatocytes binucleation. Necrosis and increase in blood vessel diameter were observed during the experimental period. The volume and number of hepatocytes per unit area also decreased, but it was possible to verify the recovery of these parameters over time of exposure. The MCYST has accumulated in hepatocytes and can be detected until the last analysis time. In the liver of rats, the same histopathological pattern was observed in 24 h. A possible oxidative damage was found in liver and kidney justified by the change of CAT activity and the relationship GSH / GSSG. The kidney index in rat was increased at 24 h, indicating a possible edema. It was observed that the rats intoxicated decreased food intake and feces production, and increased of drink ingestion and elimination of urine. Similarly, the glomerular filtration rate increases in animals exposed to toxin. There was a greater elimination of MCYST in the free form in the urine in 24 h, even though only 14% of the administered dose had been eliminated. However, the fractional excretion of the same was 137.9 ± 9.1%, indicating secretion process. The results of this study confirm the presence of MCYST-LR in mice exposed to a single dose of MCYST. In addition, there were metabolic and functional alterations in the kidneys of rats exposed. These results confirm the necessity for more studies despite of sublethal exposures to MCYST.