Trimetazidine, a metabolic modulator, attenuates silica‐induced pulmonary fibrosis and decreases lactate levels and LDH activity in rats

Abstract

Pulmonary fibrosis has been recently linked to metabolic dysregulation. Silicainduced pulmonary fibrosis in rats was employed by the current study to explore the effects of trimetazidine (a metabolic modulator-antianginal drug; TMZ) on silicainduced pulmonary fibrosis. Pulmonary fibrosis was induced by intranasal instillation of silica (50 mg/100 µl/rat) in TMZ versus vehicle-treated rats. Body weights of rats, weights of lungs, and wet-to-dry lung weights were determined. Various parameters were also measured in serum, bronchoalveolar lavage fluid (BALF) in addition to lung tissue homogenates. Moreover, histopathological examination of sectioned lungs for lesion score and distribution and histochemical detection of myeloperoxidase (MPO) in lung tissues were also performed. No significant differences were observed in body weight gains, lung coefficients, lung weights, and wet-to-dry lung weight in silica versus control rats. Elevated lactate levels in serum and lung homogenates were significantly attenuated by TMZ. In addition, lactate dehydrogenase activity, transforming growth factor-β, and total proteins in BALF were significantly normalized with TMZ. Moreover, TMZ significantly increased reduced glutathione and adenosine triphosphate levels and decreased nitrate/nitrite and hydroxyproline content in lungs of silica-treated rats. Histopathological examination of lungs revealed more than 56% reduction in lesion score and distribution by TMZ. MPO expression in lungs of silica-treated rats was also significantly attenuated by TMZ.TMZ attenuates silica-induced pulmonary fibrosis, an effect that could be mediated by suppressing anaerobic glycolysis-induced excessive lactate production. Regulation of oxidative stress could also play a role in TMZ-promoted protective effects.

Animal models of acute exacerbation of pulmonary fibrosis

“…Western blot analysis of lung lysates revealed elevated levels of collagen I and fibronectin in the silicosis group, collectively demonstrating silica-induced pulmonary fibrosis in mice [86]. Similarly, several studies have confirmed that intranasal silica instillation can induce pulmonary fibrosis in both mice and rats [87][88][89].…”

Unmasking the Warburg Effect: Unleashing the Power of Enzyme Inhibitors for Cancer Therapy

“…Silica-induced pulmonary fibrosis studies in rats were done to explore the effects of this drug over the LDH activity. The results showed that the derivative of compound 93 was able to reduce and normalize the levels of the enzyme in bronchoalveolar lavage fluid (BALF) [164]. TMZ can be used alone or in combination with antineoplastic drugs, such as gemcitabine or abraxane, to reduce cell viability and induce apoptosis in human pancreatic cancer cells [165].…”