Abstract
3,3′-Diindolylmethane (DIM), a metabolic product of indole-3-carbinol extracted from cruciferous vegetables exhibits anti-inflammatory and anti-cancer properties. Earlier, the product has been demonstrated to possess anti-fibrotic properties; however, its protective effects on liver injury have not been clearly elucidated. In this study, we postulated the effects and molecular mechanisms of action of DIM on carbon tetrachloride (CCl4)-induced liver injury in mice. Acute liver injury was induced by a single intraperitoneal administration of CCl4 (1 ml/kg) into mice. DIM was injected via subcutaneous route for three days at various doses (2.5, 5 and 10 mg/kg) before CCl4 injection. Mice were sacrificed and serum was collected for quantification of serum transaminases. The liver was collected and weighed. Treatment with DIM significantly reduced serum transaminases levels (AST and ALT), tumor necrosis factor-α (TNF-α) and reactive oxygen species (ROS). CCl4- induced apoptosis was inhibited by DIM treatment by the reduction in the levels of cleaved caspase-3 and Bcl2 associated X protein (Bax). DIM treated mice significantly restored Cytochrome P450 2E1, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression in CCl4 treated mice. In addition, DIM downregulated overexpression of hepatic nuclear factor kappa B (NF-κB) and inhibited CCl4 mediated apoptosis. Our results suggest that the protective effects of DIM against CCl4- induced liver injury are due to the inhibition of ROS, reduction of pro-inflammatory mediators and apoptosis.
Highlights
The liver, a vital organ, acts as an accessory digestive gland that produces biochemicals necessary for digestion, detoxifies various metabolites and synthesizes proteins
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Summary
The liver, a vital organ, acts as an accessory digestive gland that produces biochemicals necessary for digestion, detoxifies various metabolites and synthesizes proteins. Pathogenesis in the liver rises due to the involvement of numerous cytokines and growth-factor-mediators [1]. Liver injuries are reversible and are mostly self-healing [2]. The progression of repeated injury and rapid dysfunction of liver can lead to multi-organ failure and even death [3]. Liver injury can be acute or chronic resulting from multiple reasons such as viral hepatitis, drug overdose, idiosyncratic drug reaction and toxins [4]. The characteristics of liver injury have been explored extensively, but no effective therapeutic steps have been implemented [5,6]
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