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Pathol Res Pract. 2018 Dec;214(12):2115-2120. doi: 10.1016/j.prp.2018.09.030. Epub 2018 Oct 3.

Evaluation of progressive hepatic histopathology in long-term tamoxifen therapy.

Author information

1
CESPU, Institute of Research and Advanced Training in Health Sciences and Technologies, Gandra, Portugal; Center for Health Technology and Services Research (CINTESIS), Faculty of Medicine, University of Porto, Portugal.
2
Department of Biomedicine, Unit of Anatomy, Faculty of Medicine of the University of Porto, Porto, Portugal.
3
CESPU, Institute of Research and Advanced Training in Health Sciences and Technologies, Gandra, Portugal.
4
CESPU, Institute of Research and Advanced Training in Health Sciences and Technologies, Gandra, Portugal; UCIBIO/REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal; Department of Public Health and Forensic Sciences, and Medical Education, Faculty of Medicine, University of Porto, Porto, Portugal.
5
Department of Biomedicine, Unit of Anatomy, Faculty of Medicine of the University of Porto, Porto, Portugal; Center for Health Technology and Services Research (CINTESIS), Faculty of Medicine, University of Porto, Portugal. Electronic address: sasusana@med.up.pt.

Abstract

Tamoxifen (TAM) therapy is the better treatment for breast cancer and the drug use the prophylaxis of this disease in young premenopausal women. Yet, the effects associated with this therapy are unknown. To better understand the extension of this problem, we developed an animal model to mimic this therapy, aiming to evaluate its potential biochemical and histopathological changes in the liver. Young cycling female rats were treated with TAM for one, two and three months and toxicological biomarkers and liver histomorphometry were evaluated. Starting at two months, TAM-treatment prevented the normal age-dependent increase in body weight, without inducing changes in food intake. Serum levels of cholesterol and of the metabolic enzymes creatine kinase and aspartate aminotransferase were reduced in all TAM treatment periods. Serum levels of the metabolic enzymes alkaline phosphatase and lactate dehydrogenase were increased after the first month but returned to control levels upon 3 months of drug exposition. Moderate microvesicular steatosis, classified only at the first month of TAM treatment, was reduced afterwards. Our model showed an adaptive response of liver upon 3 months of treatment, suggesting that at the stated conditions, TAM will not promote hepatotoxicity. In this way, the present model may be useful in the study of possible key endocrine effects of TAM use and the search for better clinical outcomes.

KEYWORDS:

Cycling female rats; Hepatotoxicity; Metabolic profile; Pilot study; Tamoxifen

PMID:
30314755
DOI:
10.1016/j.prp.2018.09.030
[Indexed for MEDLINE]

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