Pirfenidone ameliorates dexamethasone-induced steatohepatitis and vascular resistance in rats

In clinics, glucocorticoids (GC) are frequently recommended as immunosuppressive and anti-inflammatory medications. The side effects of GC are the main concerns, which mostly include insulin resistance (IR), vascular changes, and fatty liver. Knowing the mechanism underlying GC-induced hepatic steatosis and vascular alterations helps identify a target to prevent these side effects.

The target of this investigation was to assess the beneficial influences of pirfenidone (PFD) versus dexamethasone (DEX)-induced steatohepatitis and vascular resistance.

Rats were classified haphazardly into five categories: control group, PFD control group, DEX group and two groups received PFD for 14 days (50 and 100 mg/kg) by oral route and injected with DEX (1 mg/kg) over the second week of the study.

PFD reverted morphological alterations, mitigate oxidative dysfunctions, elevated lipid profile and normalize liver transaminases. PFD also attenuated inflammatory markers, PFD also downregulated aortic NF-κB, JNK, ET-1, VCAM and VEGF that were dysregulated by DEX. Moreover, hepatic and aortic IRS1, AKT, P-AKT (ser⁴⁷³) level, aortic eNOS and CD34 levels were elevated upon PFD treatment. Furthermore, PFD pretreatment decreased hepatic and aortic levels of autophagy biomarkers.

PFD may provide hepato- and vasculo-protective effects via its insulin-sensitization, hypoglycemic, hypolipidemic, antioxidant and anti-inflammatory activities.