N-acetylcysteine+nimesulide: An association strategy aiming to prevent nimesulide-induced hepatotoxicity
DOI:
https://doi.org/10.12957/bjhbs.2020.59709Keywords:
Nimesulide, N-acetylcysteine, Safety, Hepatotoxicity, Anti-inflammatory.Abstract
Introduction: Nimesulide is a potent anti-inflammatory
with rapid and long-lasting effects, but also with a high risk
of hepatotoxicity. Objective: This work aimed to prevent
nimesulide-induced hepatotoxicity through the association
of nimesulide with a hepatoprotective agent. Materials and
Methods: First, we tested three hepatoprotective agents:
N-acetylcysteine, L-carnitine, and Gingko biloba extract in
an in vitro hepatic cell model. Both N-acetylcysteine and G.
biloba showed promisor results. We selected N-acetylcysteine
to continue the studies in an animal model. In vivo study was
performed using male Wistar rats divided in 4 groups: control,
nimesulide (100mg/kg/day), nimesulide (100mg/kg/day) +
N-acetylcysteine (100mg/kg/day) and N-acetylcysteine alone
(100mg/kg/day). Treatments were given by gavage, daily, for
15 days. Results: Animals receiving nimesulide alone showed
lower body weight gain compared to control. Body weight
gain in the nimesulide + N-acetylcysteine group was higher
than nimesulide alone, evidencing lower toxicity. However,
the body weight gain of the nimesulide + N-acetylcysteine
group was still lower than the control animals. Animals treated
with nimesulide alone presented an increased relative mass of
heart, liver, and spleen and significant hepatic damage seen in
microscopy when compared to other groups. N-acetylcysteine
co-administered with nimesulide prevented the increased
heart mass, but the same was not true with liver and spleen.
Conclusions: This work evidence partial protection elicited
by the association of N-acetylcysteine and nimesulide against
nimesulide-induced hepatotoxicity.
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