Hepatic dysfunction induced by 7, 12-dimethylbenz(α)anthracene and its obviation with erucin using enzymatic and histological changes as indicators.

Rohit Arora,Saroj Arora,Rakesh Kumar,Sakshi Bhushan,Pardeep Kaur,Deepika Sharma,Rahul Mannan,Adarsh P Vig,Amrit Pal Singh,Bikram Singh,Jordi Gracia-Sancho

doi:10.1371/journal.pone.0112614

Abstract

The toxicity induced by 7, 12-dimethylbenz(α)anthracene (DMBA) has been widely delineated by a number of researchers. This potent chemical damages many internal organs including liver, by inducing the production of reactive oxygen species, DNA-adduct formation and affecting the activities of phase I, II, antioxidant and serum enzymes. Glucosinolate hydrolytic products like isothiocyanates (ITCs) are well known for inhibiting the DNA-adduct formation and modulating phase I, II enzymes. Sulforaphane is ITC, currently under phase trials, is readily metabolized and inter-converted into erucin upon ingestion. We isolated erucin from Eruca sativa (Mill.) Thell. evaluated its hepatoprotective role in DMBA induced toxicity in male wistar rats. The rats were subjected to hepatic damage by five day regular intraperitoneal doses of DMBA. At the end of the protocol, the rats were euthanized, their blood was collected and livers were processed. The liver homogenate was analyzed for phase I (NADPH-cytochrome P450 reductase, NADH-cytochrome b5 reductase, cytochrome P450, cytochrome P420 and cytochrome b5), phase II (DT diaphorase, glutathione-S-transferase and γ-glutamyl transpeptidase) and antioxidant enzymes (superoxide dismutase, catalase, guaiacol peroxidise, ascorbate peroxidise, glutathione reductase and lactate dehydrogenase). The level of thiobarbituric acid reactive substances, lipid hydroperoxides, conjugated dienes and reduced glutathione in the liver homogenate was also analyzed. The serum was also analyzed for markers indicating hepatic damage (alkaline phosphatase, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, direct bilirubin and total bilirubin). Erucin provided significant protection against DMBA induced damage by modulating the phase I, II and antioxidant enzymes. The histological evaluation of liver tissue was also conducted, which showed the hepatoprotective role of erucin.

Highlights

Polycyclic aromatic hydrocarbons (PAHs) are atmospheric pollutants dispersed abundantly in the ecosystem and are even detected in cooked foods [1], [2]
Isolation of Erucin Erucin was successfully isolated from the extract of Eruca sativa (Mill.) Thell
The specific activity in the other groups treated with erucin was reduced towards the normal level

Summary

Introduction

Polycyclic aromatic hydrocarbons (PAHs) are atmospheric pollutants dispersed abundantly in the ecosystem and are even detected in cooked foods [1], [2]. Amid the various classes of PAHs, 7, 12-dimethylbenz(a)anthracene (DMBA) is a well known carcinogen and immunosuppressor used in rodent models to study cancer [3] (Figure 1A). DMBA is reported to induce mutations by making DNA adducts [4], [5]. It is a well known skin carcinogen, yet many researchers have reported the deleterious effect of DMBA in liver [6], [7], [8]. Liver is the primary site of metabolism and is often prone to damage by xenobiotics. Liver cancer is the second most common cause of cancer deaths worldwide [9]

Methods

Results

Conclusion