Alterations in Thiol/disulphide Homeostasis of Acute Lung Toxicity of Bleomycin in Rats

Bleomycin (BLM)-induced pulmonary fibrosis, a progressive and lethal form of interstitial lung disease, is mediated through the generation of reactive oxygen species. Since the dynamic thiol/disulphide homeostasis is a substantial marker for oxidative stress, for future glutathione based methodological researches on the progressive BLM toxicity in lungs, it is very valuable to show that the toxic mechanism. We investigated the dynamic thiol/disulphide homeostasis in a rat model with BLM-induced pulmonary fibrosis. BLM (5 mg/kg) or saline was injected into the lungs as 0,1 ml by insuline syringe that inserted into gently opened trachea of anesthetized rats. Native thiol (SH), total thiol (total SH), and disulphide (SS) levels were measured in rat serum at pre-treatment, 24th hour, 2nd, 4th, 7th, 14th, and 28th days of BLM treatment, with a novel automated method recently described. The levels of native SH and total SH in BLM group were decreased at 24th hour and this reduction were gradually continued up to 28th day when compared with pre-treatment BLM and/or the saline control group. On the other hand there were significantly a high ratio in BLM group with %SS/SH at 4th day and %SS/total SH at 4th and 28th days while there was no difference at 7th and 14th days. Results clearly indicate that the thiol/disulphide homeostasis can be acutely disturbed in the experimental model of BLM-induced fibrosis. So this data offer a new modeling option to discuss the therapy strategies and the effect mechanisms of BLM-induced lung toxicity.