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Updated: Oct 3, 2025

Establishment and Validation of a Rat Model of Pulmonary Arterial Hypertension Associated with Pulmonary Fibrosis
Published on: May 23, 2025
Polydatin combats methotrexate-induced pulmonary fibrosis in rats: Involvement of biochemical and histopathological
Yomna A Ali1, Amany A E Ahmed2, Ola M Abd El-Raouf1
1Department of Pharmacology, Egyptian Drug Authority (EDA), Formerly National Organization for Drug Control and Research, Cairo, Egypt.
Abstract:
Polydatin (PD) is a polyphenolic compound found naturally in many fruits such as grapes. It has anti-oxidant and anti-inflammatory activities that are of paramount importance for its pharmacological actions. This study aimed to explore possible protective effects of PD against methotrexate (MTX)-induced pulmonary fibrosis in rats. A single oral dose of MTX (14 mg/kg) per week for 2 weeks caused a significant decrease in glutathione (GSH) content with a marked increase in transforming growth factor-beta (TGF-β), alpha-smooth muscle actin (α-SMA), pulmonary content of malondialdehyde (MDA), interleukin-1β (IL-1β), Hydroxyproline, tumor necrosis factor-alpha (TNF-α), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) as compared with the control group. Contrarily, daily administration of PD (25, 50, and 100 mg/kg, p.o.) for 14 days concomitantly with MTX ameliorated MTX-induced pulmonary fibrosis as indicated by mitigation of the previously mentioned biochemical parameters and histopathological changes in a dose-dependent manner. In conclusion, the protective effect of PD against pulmonary fibrosis induced by MTX in rats might be attributed to its anti-oxidant, anti-inflammatory as well as anti-fibrotic effects.

