Protective effect of acrocarpus fraxinifolius extract against hepatic fibrosis induced by Gamma irradiation and carbon tetrachloride in albino rats

Abstract

Purpose

Liver fibrosis is considered as one of the ultimate outcomes of chronic liver disorders, characterized by outrageous cell proliferation and abnormal deposition of extracellular matrix, resulting in sever pathological distortions in the architecture and performance of liver tissues. The present study aimed to investigate the protective properties of aqueous methanol extract of Acrocarpus fraxinifolius leaves (AFL) against liver fibrosis induced by dual toxicity of γ-irradiation and carbon tetrachloride (CCl₄) in rats.

Methods

The animals were exposed to 2 Gy irradiation once/week concurrently with intraperitoneal administration of CCl₄ (0.2 mL/100 g body weight) for seven weeks. Afterwards, liver toxicity and fibrosis were assessed biochemically at cellular and molecular as well as histopathological levels.

Results

The livers of intoxicated rats showed distinct structural and functional changes, compared with the normal rats. The administration of AFL (500 mg/kg, p.o) significantly ameliorated the histopathological manifestations of fibrotic liver evidenced by mitigated steatosis progression, necrosis, fibrotic septa, apoptotic bodies, and immunochistochemical studies of alpha-smooth muscle actin. Also, AFL increased the final body weight, total protein, albumin levels and albumin/globulin ratio. While, the absolute liver weight, liver enzymes, total cholesterol and triglycerides were reduced. A significant modulation was observed in hydroxyproline, transforming growth factor-β and collagen-1expression. Furthermore, AFL exerted a direct effect on liver fibrosis by promoting extracellular matrix degradation via overexpression of the tissue inhibitor metalloproteinase-1, coupled with decease of metalloproteinase-9 activity.

Conclusions

Our findings suggested that AFL effectively improved the architecture of fibrotic liver and modified the biochemical markers of liver fibrosis.

Graphical Abstract

Keywords:

• Liver
• fibrosis
• carbon tetrachloride
• radiation
• Acrocarpus fraxinifolius
• metalloproteinase

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The authors would like to thank the Research Sector of Ain Shams University, Cairo, Egypt (NO: M/78/1) for providing partial funding for this work.

Notes on contributors

Omama E. El-Shawi

Omama E. El-Shawi, PhD, is a professor of biochemistry at Health Radiation Research Department, National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt.

Heba A. S. El-Nashar

Heba A. S. El-Nashar, PhD, is an assistant professor of pharmacognosy, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo, Egypt and a researcher at Drug Discovery Research and Development center, Ain Shams University, Egypt.

Sahar S. Abd El-Rahman

Sahar S. Abd El-Rahman, PhD, is an associate professor of pathology, Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt.

Omayma A. Eldahshan

Omayma A. Eldahshan, PhD, is a professor of pharmacognosy, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo, Egypt and a member of foundation committee of Drug Discovery Research and Development center, Ain Shams University, Egypt.

Abdel Nasser B. Singab

Abdel Nasser B. Singab, PhD, is a professor of Pharmacognosy, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo, Egypt and Chief Executive Officer (CEO) of Drug Discovery Research and Development center, Ain Shams University, Egypt.