Assessment the oxidative stress potential of fluoxetine and amitriptyline at maximum therapeutic doses for four-week treatment in experimental male rats

Abstract

Nowadays, the contribution of oxidative stress (OS) to the safety profile of medications at a
specific doses remains widely undetermined. Antidepressants are known to be used over a longterm
periods and the incidence of their toxicities due to accumulative OS cannot be excluded.
Therefore, the aim of this study was to investigate the possible oxidative damage of the
commonly used antidepressants (fluoxetine and amitriptyline) besides their histopathological
effects in adult male rats.
Selected parameters of OS (MDA and SOD) in addition to histopathological changes have been
examined in liver and testis tissues of 24 Swiss albino adult male rats; the animals were randomly
allocated into three groups of 8 rats each: Group I - rats orally-administered distilled water via
gavage tube for four weeks as a negative control. Group II - rats orally-treated with fluoxetine
hydrochloride solution (7.2mg/kg/day) via gavage tube for four weeks. Group III - rats orallytreated
with amitriptyline hydrochloride solution (27mg/kg/day) via gavage tube for four weeks.
The results revealed that both drugs (Group II and Group III) induced the same extent of
oxidative damage, as evidenced by a significant elevation of MDA contents and a marked
reduction of SOD levels in hepatic and testicular tissue homogenates as compared with the
negative control (Group I), which have been confirmed by histopatholgical alterations.
These findings indicates that both fluoxetine and amitriptyline have cytotoxic potentials and can
induce the same extent of oxidative damage in rats. Special precautions and medical supervision
should be taken in consideration with their uses.