Chitosan-Glutathione Nanoparticles Modify Hepatic Cellular Response on Bovine Precision-cut Liver Slices Treated With Zilpaterol and Clenbuterol.

Abstract

\n Zilpaterol and clenbuterol are two β-adrenergic agonist drugs used on animal production. Both drugs have anabolic effects with advantages on carcass yield. Meanwhile, zilpaterol is approved for animal feed in authorized countries; clenbuterol is a banned substance due to the risk of toxicity; however, it is still being used at unknown dose levels in many farm species. Therefore, the use and abuse of these substances should be closely monitored, considering the clenbuterol ability and the not proven yet of zilpaterol to produce reactive oxygen (ROS) and nitrogen species. Regarding glutathione which is the main intracellular antioxidant and plays detoxification functions on liver metabolism; case study is a primary interest to know the capacity of chitosan-glutathione nanoparticles (CS/GSH-NP) as a complementary source of exogenous GSH to modify the oxide-reduction status on bovine precision-cut liver slice cultures exposed to clenbuterol and zilpaterol. A single drug assay was performed in the first instance by adding clenbuterol, zilpaterol, chitosan nanoparticles (CS-NP), and CS/GSH-NP. Then combinate drug assay was carried out by testing clenbuterol and zilpaterol combined with CS-NP or CS/GSH-NP. The results showed that both agonist β-adrenergic modify in a dose-dependent manner oxide-reduction response through ROS generation, glutathione peroxidase activity, and intracellular GSH content; and de release of liver enzymes associated with hepatocellular damage like gamma glutamyl-transpeptidase, aspartate aminotransferase, alanine aminotransferase. The exogenous GSH delivered by nanoparticles could be used to modulate these markers.