Effects of metformin on CCl4-induced pulmonary fibrosis via autophagy pathway in rats: a histological, electron microscopic, and immunohistochemical study.

Abstract

Lung fibrosis is defined as fibrotic change of the lung architecture within 2.5-3 years of diagnosis, ultimately leading to respiratory failure and death. Prolonged exposure to high concentrations of carbon tetrachloride, especially vapor, can cause lung destruction. Autophagy was crucial for maintaining the organs' homeostasis. Deficit in autophagy has been commonly associated with fibrosis and pneumonia. Recent research suggests that metformin may provide protection against a variety of lung ailments. To investigate how metformin protects against lung damage caused by carbon tetrachloride via the autophagy pathway, 30 adult male albino rats (10 rats each) were divided into three equal groups. One group served as the control. Group 2: received CCl4 1.5 mg/kg twice weekly S.C. for a duration of 12 weeks. Group 3: Oral metformin and CCl4 were administered for 12 weeks at a dose of 100 mg/kg/day and 1.5 mg/kg twice weekly S.C. After the animal died, its lungs were taken out of each group and studied under an electron and light microscope in addition to being used for immunological research. The histological abnormalities in the lung tissue caused by the administration of CCl4 included areas of tissue destruction, congestion, and fibrosis. Pneumocyte type I, type II, and collagen fiber deposition were found to have changed ultrastructurally. Concurrent metformin and CCl4 treatment resulted in improvements. The histological and biochemical effects of CCl4 on lung tissue can be modulated by administration of metformin.