Thiol reducing agents abate cholestasis-induced lung inflammation, oxidative stress, and histopathological alterations

Cholestasis is the stoppage of bile flow which can damage many organs. In this context, lung injury is a critical secondary organ damage associated with cholestasis/cirrhosis. Unfortunately, there are no specific pharmacological options against cholestasis-associated lung injury. On the other hand, it has been found that oxidative stress plays a crucial role in this complication. Hence, the current study was designed to investigate the effect of N-acetyl cysteine (NAC) and dithiothreitol (DTT) as robust thiol-reducing and antioxidant agents against cholestasis-induced lung injury. Bile duct ligated (BDL) rats were monitored for the presence of inflammatory cells, TNF-α, and IgG levels in their broncho-alveolar fluid (BALF) at scheduled time intervals (۳, ۷, ۱۴, and ۲۸ days post-BDL surgery). These markers reached their highest level in the BALF of BDL rats on day ۲۸ after the surgery. Therefore, the BDL animals were treated with NAC (۱۰۰ and ۳۰۰ mg/kg/day, i.p) and DTT (۱۰ and ۲۰ mg/kg/day, i.p) for ۲۸ consecutive days. A significant increase in BALF levels of TNF-α and IgG was detected in the BALF of BDL rats. The BALF level of neutrophils, monocytes, and lymphocytes was also significantly increased in cholestatic animals. A significant alteration in oxidative stress parameters and histopathology was detected in the BDL rats. It was found that NAC and DTT could significantly blunt pulmonary damage induced by cholestasis. The effects of these agents on oxidative stress biomarkers and inflammation seem to play a pivotal role in their mechanisms of protective properties in the lung of BDL rats.

Keywords:

Bile acid , Cirrhosis , Cholestasis , Inflammation , Oxidative stress , Pulmonary injury