ANTIFIBROTIC EFFECTS OF ANGIOTENSIN RECEPTOR BLOCKERS IN ORGANOPHOSPHATE (CHLORPYRIFOS) INDUCED LIVER FIBROSIS

Main Article Content

Aftab Abbasi
Samreen Memon
Salman Ahmed Farsi Kazi

Keywords

Liver fibrosis, chlorpyrifos, angiotensin receptor blockers, collagen, alpha smooth muscle actin

Abstract

Background: Organophosphates (OPs) are one of the pesticides causing toxicity to humans and animals. OPs toxicity involve many organs such as liver, kidney, nervous system and immune system. Liver fibrosis is a wound healing response in which there is increased production and deposition of extracellular matrix (ECM), due to prolonged injury to liver by viral hepatitis, alcohol consumption, metabolic diseases and toxins (pesticides). Angiotensin receptor blockers (ARBs) are potential therapeutic agents for liver fibrosis.


Objectives: To determine the effects of ARBs on Chlorpyrifos(CPF) induced liver fibrosis.


Methods: 40 adult male albino wistar rats were used in the study. Rats were grouped as control group (A1), positive control group (A2) and experimental groups (B, C and D). Group A2 was treated with carbon tetrachloride (CCL4) to induce liver fibrosis, with 2 ml/kg of 50% solution of CCL4 by oral gavage two times per week for eight weeks, group B was treated with 1ml/bw/day CPF intraperitoneally for eight weeks. Group C was treated with 1ml/bw/day CPF intraperitoneally for eight weeks and then ARBs orally (30mg/kg/day) for 8 weeks. Group D was simultaneously treated with CPF and ARBs for 8 weeks with same doses as for group C. At the end of experiment blood was collected by cardiac puncture for liver function test and rats were sacrificed to collect liver samples. Pathological changes in liver were examined using H&E and Masson’s trichrome staining. Real time PCR was used to detect alpha smooth muscle actin (α-SMA), transforming growth factor beta 1(TGF- β1) and Collagen-I(coll-I) mRNA expression.


Results: CPF caused liver injury evidenced by raised liver enzymes and bilirubin with histological changes and increased expression of genes. ARBs decreases liver enzymes, CPF induced histological changes and decreases the expression of α-SMA, TGF- β1 and Coll-I.


Conclusion: The present study suggests that ARBs prevent fibrogenesis and may serve as a promising therapeutic agent to reduce CPF induced liver fibrosis.

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