Synergistic, Attenuative and Modulatory Activity in Dimethylnitrosamine (DMN)-induced Fibrotic Rats Treated with Vernonia Amygdalina and Annona Muricata Leaves

¹ Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medical Sciences, Edo University, Iyamho, Edo state, Nigeria

² Department of Biochmistry, Faculty of Life Sciences. University of Benin, Edo State, Nigeria

^*Corresponding Author

Usunobun Usunomena

Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medical Sciences

Edo University, Iyamho, Edo state

Nigeria

Email: usunobun.usunomena@edouniversity.edu.ng

Phone: +2348034174871

Abstract

Background: This study assessed the effect of Vernonia amygdalina and Annona muricata leaves in a combine dose on oxidative stress and extracellular matrix parameters in liver fibrosis induced by dimethylnitrosamine (DMN).

Methods: One group, the control received physiological saline; Second group was given 100mg/kg each of Vernonia amygdalina and Annona muricata ethanol leaf extract without DMN orally for 14 consecutive days. The third group received intra-peritoneal injection of 10mg of DMN/kg body weight three times a week (on the first three days) for two weeks, in addition to 100mg/kg each of Vernonia amygdalina and Annona muricata which were administered for 14 days consecutively while the last group was given only 10mg of DMN/kg. 14 days later, the rats were sacrificed, blood samples collected and sera analysed for hyaluronic acid (HA), alkaline phosphatase (ALP), alanine transaminase (ALT) and aspartate transaminase (AST) while collagen, catalase (CAT), reduced glutathione (GSH), superoxide dismutase (SOD) and malondialdehyde (MDA) levels were assayed in liver tissue homogenate.  Sections of liver tissue were also fixed in formol-saline and subjected to histological analysis.

Results: DMN administration caused significant increases in kidney weight, serum ALP, AST, HA, ALT and in liver total collagen content and MDA (P < 0.05) and a significant drop in body and liver weight, liver CAT, GSH and SOD. Histological examination of liver showed that DMN caused congestion, centrilobular, haemorrhagic necrosis, thick collagen fibers deposition and fibrosis. However a combination of 100mg/kg each of Vernonia amygdalina and Annona muricata leaves remarkably attenuated and modulated above DMN-induced changes.

Conclusion: This study suggest that combination of Vernonia amygdalina and Annona muricata leaves possess fibrosuppressant, anti-oxidant and anti-hepatotoxic properties against DMN-induced hepatic fibrosis.

Keywords:Annona muricata, Dimethylnitrosamine, Fibrosis, Liver, Vernonia amygdalina

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