Trimetazidine, a metabolic modulator, attenuates silica-induced pulmonary fibrosis and decreases lactate levels and LDH activity in rats.
glycolysis
lactate
pulmonary fibrosis
silica
trimetazidine
Journal
Journal of biochemical and molecular toxicology
ISSN: 1099-0461
Titre abrégé: J Biochem Mol Toxicol
Pays: United States
ID NLM: 9717231
Informations de publication
Date de publication:
Jul 2022
Jul 2022
Historique:
revised:
07
02
2022
received:
21
06
2021
accepted:
29
03
2022
pubmed:
12
4
2022
medline:
20
7
2022
entrez:
11
4
2022
Statut:
ppublish
Résumé
Pulmonary fibrosis has been recently linked to metabolic dysregulation. Silica-induced pulmonary fibrosis in rats was employed by the current study to explore the effects of trimetazidine (a metabolic modulator-antianginal drug; TMZ) on silica-induced 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.
Substances chimiques
Lactates
0
Protective Agents
0
Silicon Dioxide
7631-86-9
Trimetazidine
N9A0A0R9S8
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e23071Informations de copyright
© 2022 Wiley Periodicals LLC.
Références
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