Polydatin combats methotrexate-induced pulmonary fibrosis in rats: Involvement of biochemical and histopathological assessment.

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-ß), alpha-smooth muscle actin (α-SMA), pulmonary content of malondialdehyde (MDA), interleukin-1ß (IL-1ß), 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.

Assessment of PKA and PKC inhibitors on force and kinetics of non-failing and failing human myocardium.

AIMS: Heart failure (HF) is a prevalent disease that is considered the foremost reason for hospitalization in the United States. Most protein kinases (PK) are activated in heart disease and their inhibition has been shown to improve cardiac function in both animal and human studies. However, little is known about the direct impact of PKA and PKC inhibitors on human cardiac contractile function. MATERIAL AND METHODS: We investigated the ex vivo effect of such inhibitors on force as well as on kinetics of left ventricular (LV) trabeculae dissected from non-failing and failing human hearts. In these experiments, we applied 0.5 µM of H-89 and GF109203X, which are PKA and PKC inhibitors, respectively, in comparison to their vehicle DMSO (0.05%). KEY FINDINGS AND CONCLUSION: Statistical analyses revealed no significant effect for H-89 and GF109203X on either contractile force or kinetics parameters of both non-failing and failing muscles even though they were used at a concentration higher than the reported IC50s and Kis. Therefore, several factors such as selectivity, concentration, and treatment time, which are related to these PK inhibitors according to previous studies require further exploration.