Chlorpromazine

Cimetidine

Amino acid

Biology

Thioridazine

Reactive oxygen species

Biochemistry

Glutathione

Organic chemistry

Toxicity

Lipid peroxidation

Oxidative phosphorylation

Oxidative stress

Antioxidant

Enzyme

Mitochondrion

Pharmacology

Medicine

Chemistry

Taurine

Acetylcysteine

Pharmaceutical Chemistry Journal

Thioridazine (TZ) is used commonly in the treatment of schizophrenia. However, its clinical use has been associated with liver toxicity. Therefore, we examined the cytotoxic effect of TZ on freshly isolated rat hepatocytes to evaluate the role of TZ pathogenesis in hepatotoxicity. In addition, the effect of N-acetylcysteine (NAC), taurine, and cimetidine on this toxicity was investigated. Cell death, reactive oxygen species (ROS) formation, lipid peroxidation (LPO), cellular glutathione (GSH) content, and mitochondrial depolarization were assessed as toxicity markers. Results showed that TZ caused an increase in ROS formation as well as LPO and GSH depletion. Moreover, mitochondrion seems to be targets of TZ-induced toxicity. The severe hepatotoxicity of TZ in enzyme-induced rats suggests the potential role of reactive intermediates. The present study proposes the protective effect of NAC and/or taurine against TZ-induced cellular injury, probably through their radical scavenging properties and effects on mitochondria.

The Effects of Cimetidine, N-Acetylcysteine, and Taurine on Thioridazine Metabolic Activation and Induction of Oxidative Stress in Isolated Rat Hepatocytes