Protective effects of tetrandrine on brain cells in phenobarbital-dependent and -withdrawn rats

Abstract

The aim of this study was to investigate the effects of tetrandrine (Tet) on the brain cells of phenobarbital-dependant and -withdrawn rats, and to explore the underlying mechanisms. A total of 100 rats were randomly divided into five groups: The control group, the phenobarbital-dependent model group, and Tet-treated groups of low-, mid-and high-dosages. Following drug withdrawl, the morphological changes of the frontal lobe cells were examined by hematoxylin and eosin (H&E) staining. Immunohistochemical staining was applied to detect the expression of apoptosis-related proteins Bcl-2 and Bax. Reverse transcription-polymerase chain reaction (RT-PCR) and western blotting methods were applied to detect the mRNA and protein expression levels of Bcl-2 and Bax, respectively, in the frontal lobe. The results indicated that Tet effectively reduced the withdrawal symptoms, particularly the weight loss, in phenobarbital-dependent and -withdrawn rats. H&E staining revealed that Tet significantly restored the histopathological changes in the addicted rats in a dose-dependent manner. The immunohistochemical, RT-PCR, and western blot analyses indicated that Tet treatment significantly increased the Bcl-2+ brain cells and the mRNA and protein expression levels of Bcl-2, and decreased the Bax+ cells and the mRNA and protein expression levels of Bax, as well as elevated the ratio of Bcl-2/Bax, in phenobarbital-dependent and -withdrawn rats. Tet may inhibit apoptosis in these addicted rats, in a dose-dependent manner. Tet alleviates the phenobarbital withdrawal symptoms and protects the brain cells against apoptosis, which may be a result of the regulation of the mRNA and protein expression levels of Bcl-2 and Bax.