Abstract

The current study was aimed to evaluate the preventive effects of Indigofera oblongifolia leaf extract (IOLE) on lead acetate (PbAc)-induced hepatotoxicity in adult male Wistar rats. PbAc was intraperitoneally injected at a dose of 20 mg/kg body weight for 5 days alone or in combination with the IOLE (100 mg/kg). Liver lead concentration and oxidative stress markers such as lipid peroxidation, hydrogen peroxide, nitric oxide, and glutathione content were investigated in addition to the enzymatic antioxidant activities. PbAc injection caused a significant elevation in the liver function parameters, lead level, lipid peroxidation, hydrogen peroxide, and nitric oxide, with a concomitant decline in the glutathione content compared with the control, accompanied by a significant inhibition of antioxidant enzyme activities. The induction of oxidative stress, lead accumulation, and histological alterations in the liver were successfully minimized by pre-administration of IOLE. In addition, the PbAc group showed increase in the levels of Bax, caspase-3, and matrix metalloproteinase-9 proteins, while the expression of Bcl-2 protein was decreased. Prior administration of IOLE significantly mitigated apoptosis and fibrosis in the liver. Finally, the major components in I. oblongifolia extract were identified as polyphenols, flavonoids, and organic acids using liquid chromatography coupled mass spectroscopy. Thus, the findings of the current study revealed that I. oblongifolia had protective, anti-fibrotic, antioxidant, and anti-apoptotic activities on PbAc-induced hepatotoxicity. The beneficial effects of I. oblongifolia were in part mediated by Nrf2/HO-1 pathway.

Highlights

  • Lead (Pb) is a toxic pollutant, and occupational as well as environmental exposures remain a global health problem

  • No mortality was recorded in rats of control and experimental groups

  • The observed increase in the liver was thought to be due to necrosis and apoptosis, and could be attributed to the accumulation of the lipids and fibrous tissue in the liver

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Summary

Introduction

Lead (Pb) is a toxic pollutant, and occupational as well as environmental exposures remain a global health problem. Continuous exposure to Pb even at low concentrations has been established as a risk factor causing hepatotoxicity, nephrotoxicity, and reproductive and behavioral dysfunctions [1,2,3]. Among the organs affected by Pb toxicity, the liver is the most common depository of Pb, followed by the kidney [4]. The liver is the first organ exposed to enterally absorbed Pb via the portal system. PLOS ONE | DOI:10.1371/journal.pone.0158965 July 8, 2016

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