Finasteride promotes worsening of the cardiac deleterious effects of nandrolone decanoate and protects against genotoxic and cytotoxic damage

Elizângela Faustino Da Mata,Andrews Marques Do Nascimento,Dominik Lenz,Denise Coutinho Endringer,Nazaré Souza Bissoli,Girlandia Alexandre Brasil,Ewelyne Miranda De Lima,Tadeu Uggere De Andrade,Ieda Carneiro Kalil

doi:10.1590/s2175-97902019000318289

Abstract

Metabolism of anabolic androgenic steroids is important for its physiological effects. The aim was to investigate the effects of finasteride (a 5α-reductase inhibitor - 5αR) on cardiac and mutagenic effects promoted by ND. Male Wistar rats were separated into three groups: CONT, received the vehicles of ND and finasteride (Peanut oil+Saline); DECA group, received ND (20 mg.kg.week-1, i.m.), and DECAF received ND and finasteride (100 µg.kg-1, i.p.), for four weeks. After, hypertrophy, cytokines and Angiotensin Converting Enzyme (ACE) activity was determined in heart. Bone marrow was used for micronucleus evaluation. Treatment with ND promotes increase in cardiac hypertrophy, ACE activity and disbalance among pro- and anti-inflammatory cytokines, and combination with finasteride worsened those effects. Association with finasteride ameliorates the toxic effects of ND on bone marrow cells, as was observed by a normalization of the number of micronucleate polychromatic erythrocytes and the mitotic index. Our data demonstrates that deleterious effects promoted by ND are depend, at least in part, of its metabolization. Also, inhibition of 5αR by finasteride present variated effects dependent on organ studied. It can promote increase on cardiac damage and a reduction on mutagenic effects of ND, which demonstrated that dehydronandrolone has diverse role on ND effects..

Highlights

Anabolic androgenic steroids (AASs) are synthetic drug analogs of the endogenous hormone testosterone
Literature reports have demonstrated the development of cardiac hypertrophy characterized by the addition of sarcomeres, which promotes an increase in the cell volume (Fernandes, Soci, Oliveira, 2011), in addition to arrhythmia and sudden death (Franquni et al, 2013; Riezzo et al, 2014)
This reduction was followed by an increase in the myocyte nucleus area (DECA 12.8%; DECAF 22.67%; Figure 1E) and the perimeter (DECA 9.1%; DECAF 15.03%; Figure 1F) compared with those in the CONT animals

Summary

Introduction

Anabolic androgenic steroids (AASs) are synthetic drug analogs of the endogenous hormone testosterone. They are used around the world to treat hypogonadism and cachexia (Kicman, 2008); the misuse of AASs by young people and adults for aesthetic purposes has increased worldwide (Lippi, Franchini, Banfi, 2011), causing many health problems for people of both sexes (Onakomaiya, Henderson, 2016). Literature reports have demonstrated the development of cardiac hypertrophy characterized by the addition of sarcomeres, which promotes an increase in the cell volume (Fernandes, Soci, Oliveira, 2011), in addition to arrhythmia and sudden death (Franquni et al, 2013; Riezzo et al, 2014). These negative effects are not limited to the cardiac system, and other negative effects are observed, such as an imbalance of inflammatory cytokines (Franquni et al, 2013; Riezzo et al, 2011), negative effects on the kidney

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