Hepatic histopathological and morphometric changes in male mice exposed to rosuvastatin from pre-puberty to adulthood: a possible adaptive hepatic response

Abstract

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.

Graphical Abstract

Keywords:

• Statin
• mice
• chronic exposure
• hepatic adaptation

Acknowledgements

The authors are thankful to the Laboratório Multiusuário de Estudos de Biologia (LAMEB) from UFSC, for supplying its infrastructure for performing some analyses; to Laboratório Veterinário Citovet, for performing the measurements of biochemical parameters; and to all colleagues who collaborated on this work.

CRediT authorship statement

Jennyfer Karen Knorst: Conceptualization, data curation, formal analysis, investigation, methodology, visualization, and writing – original draft. Tainara Fernandes de Mello: Methodology, investigation, and formal analysis. Amanda Rebonatto Oltramari: Methodology, investigation, and formal analysis. Alice Santos da Silva: Investigation and formal analysis. Gabriel Adan Araújo Leite: Conceptualization, resources, methodology, project administration, supervision, visualization, and writing – review & editing. The manuscript was revised and approved by all authors.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author, G.A.A.L, upon reasonable request.

Additional information

Funding

This study was financed in part by the Conselho Nacional de Desenvolvimento Científico e Tecnológico – Brazil (CNPq) and the authors thank CNPq for the grant. Gabriel Adan Araújo Leite was supported by CNPq grant number 404695/2023-0.