Drug and chemical toxicology · 2024
Hepatic histopathological and morphometric changes in male mice exposed to rosuvastatin from pre-puberty to adulthood: a possible adaptive hepatic response.
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Knorst Jennyfer Karen, de Mello Tainara Fernandes, Oltramari Amanda Rebonatto, da Silva Alice Santos, Leite Gabriel Adan Araújo
Аннотация
Lifestyle changes, such as poor eating habits and a reduction in physical exercise, have impaired human lipid profiles. Statins are widely used to treat dyslipidemias, of which rosuvastatin shows greater improvement in the lipid profile and may be used since childhood. This study aimed to assess the hepatic effects when male mice were given 0.9% saline solution or doses of rosuvastatin of 1.5 or 5.5 mg/kg/day from postnatal day (PND) 23 until PND 80. Body mass gain and water and food consumption were monitored during the treatment. Mice were euthanized on PND 80 when blood was collected for serum obtainment, and several organs were collected and weighed. Serum was used for evaluating lipid profiles and markers of hepatic injuries. The liver was assessed for histopathological, morphometric, and stereological changes. There was a temporary reduction in body mass gain and water and food consumption in the rosuvastatin-exposed groups. Both rosuvastatin-treated groups exhibited reduced total cholesterol levels and showed signs of hepatic tissue adaptation in response to prolonged exposure, such as sinusoidal dilation, inflammatory infiltrates, and cell death of hepatocytes. These results are considered side effects of the treatment and may indicate a hepatic adaptation to the chronic exposure.