Protective effects of methyl palmitate against silica-induced pulmonary fibrosis in rats.

Abstract

Silicosis is one of the most prevalent chronic occupational pulmonary diseases worldwide. The present study aimed to investigate the effects of methyl palmitate on silica-induced lung fibrosis in rats and explore the possible mechanisms. Male Sprague-Dawley rats were divided into 3 groups: group I served as control and group II served as positive control where rats were intranasally instilled with a single dose of silica suspension (50mg in 0.1ml saline/rat). Rats of group III received methyl palmitate (300mg/kg, I.P. three times per week at alternating days) for 60days after instillation of silica. At the end of the treatment period, animals were sacrificed then biochemical parameters and histopathology were assessed. Treatment with methyl palmitate attenuated silica-induced lung inflammation and fibrosis, as it significantly decreased lactate dehydrogenase (LDH) activity and the accumulation of the inflammatory cells in the bronchoalveolar lavage fluid (BALF). Methyl palmitate significantly reduced collagen deposition as indicated by a decrease in lung hydroxyproline content and marked attenuation in silica-induced lung fibrosis in histopathological results. In addition, methyl palmitate significantly increased superoxide dismutase (SOD) and reduced glutathione (GSH) activities with a significant decrease in the lung malondialdehyde (MDA) content. Methyl palmitate also reduced silica mediated overproduction of pulmonary nitrite/nitrate (NO2(-)/NO3(-)). Importantly, methyl palmitate decreased the level of the inflammatory cytokine tumor necrosis factor-alpha (TNF-α) in the lung. Taken together, these results demonstrate the potent protective effects of methyl palmitate against silica-induced lung fibrosis. This effect can be attributed to methyl palmitate's ability to counteract the inflammatory cells' infiltration and hence reactive oxygen species (ROS) generation and regulate cytokine effects.