Pioglitazone ameliorates hepatic damage in irradiated rats via regulating anti-inflammatory and antifibrogenic signalling pathways

Abstract

Hepatic irradiation during radiotherapy is associated with liver damage. The current study was designed to investigate the possible modulatory effects of pioglitazone against γ irradiation-induced hepatic damage in rats. Animals were exposed to a single dose of 6 Gy and received pioglitazone (10 mg/kg/day) orally for 4 weeks starting on the same day of irradiation. Results showed that irradiation increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities as well as serum triglyceride (TG) and total cholesterol (TC) levels. Furthermore, it elevated inflammatory mediators; tumour necrosis factor alpha (TNF-α), interleukin-6 (IL-6); nuclear factor kappa B (NF-κB) and inducible nitric oxide synthase (iNOS) in hepatic tissues. Moreover, it increased levels of serum fibrotic markers; hyaluronic acid (HA), laminin (LN), and type III procollagen (PCIII). Additionally, hepatic fibrotic markers; transforming growth factor-β1 (TGF-β1) and hydroxyproline (HP) levels were elevated. Histological analysis of H&E and MT staining of liver sections exhibited cellular infiltration and fibrous deposition in irradiated rats. It was observed that pioglitazone modulated the described deviations. In conclusion, pioglitazone could serve as a promising therapeutic tool for attenuating radiation-induced liver injury in patients with radiotherapy which might be attributed to its anti-inflammatory and antifibrotic activities.

Keywords:

• Gamma radiation
• hepatotoxicity
• pioglitazone

Acknowledgments

The authors are very grateful to Prof Dr. Ahmed Osman, Pathology Department, Faculty of Veterinary Medicine, Cairo University, Egypt for his assistance in examining and interpreting histopathologic aspects of this work.

Disclosure statement

No potential conflict of interest was reported by the authors.