Attenuating effect of Indole-3-Carbinol on gold nanoparticle induced hepatotoxicity in rats

Abstract

Indole-3-carbinol (I3C) is a plant based compound present in vegetables mostly belonging to cruciferous family. I3C has been shown to possess anticancer, antioxidant and anti-inflammatory properties. Humans are increasingly being exposed to GNPs due an due to their widespread and increased applications in different fields. Consistently, recent animal and cell based studies have found them to be carcinogenic, prooxidant and inflammatory. This study sought to examine the beneficial effects of I3C against oxidative stress, inflammation and histopathological changes in liver tissues of rats administered with GNPs. Forty rats randomly divided into four groups: G1 control G2, rats injected i.p. with a suspension of GNPs (10 nm in size) (20 μg/kg body wgt) for 7 days; G3, rats supplemented orally with I3C (150 mg/kg body wgt) for 7 days; and G4, rats injected with GNPs along with oral supplementation ofI3C. Compared to control, rats administered with GNPs had significantly increased liver functional markers including ALT, AST, ALP, total and direct bilirubin and significantly decreased albumin levels. GNP administered rats also demonstrated increased oxidative stress and inflammatory markers, MDA, 8-OHdG and IL-6 levels and significantly depleted activities of antioxidants such as glutathione reductase (GR) and glutathione S-transferase (GST), and transcription factor, Nrf2 compared to control. GNPs also exerted marked histological changes in liver tissues. Treatment with I3C significantly restored the GNP induced changes in the levels of all the studied parameters and also prevented pathological changes in liver tissues. Molecular docking studies confirm the interaction of I3C with hepatic cell surface receptor protein LT3 and thereby blocking GNPs from binding to I3C, confirming above experimental findings. Collectively, the data demonstrate the hepatoprotective effects of I3C against GNP-induced adverse effects on liver tissue. These protective effects of I3C appear to be mediated by its ability to downregulate oxidative stress and inflammation. Thus dietary intake of plant products rich in I3C may have beneficial health effects.