Inflammatory stress potentiates emodin-induced liver injury in rats

Abstract

Herbal medicines containing emodin, widely used for the treatment of hepatitis in clinic, have been reported with hepatotoxicity in individuals. A modest inflammatory stress potentiating liver injury has been linked to the idiosyncratic drug-induced liver injury (IDILI). In this study, we investigated the hypothesis that lipopolysaccharide (LPS) interacts with emodin could synergize to cause liver injury in rats. Emodin (ranging from 20, 40, to 80 mg/kg), which is in the range of liver protection, was administered to rats, before LPS (2.8 mg/kg) or saline vehicle treatment. The biochemical tests showed that non-toxic dosage of LPS coupled with emodin caused significant increases of plasma ALT and AST activities as compared to emodin alone treated groups (P < 0.05). In addition, with LPS or emodin alone could not induce any changes in ALT and AST activity, as compared with the control group (0.5% CMC-Na treatment). Meanwhile, the plasma proinflammatory cytokines, TNF-α, IL-1β, and IL-6 increased significantly in the emodin/LPS groups compared to either emodin groups or the LPS (P < 0.05). Histological analysis showed that liver damage was only found in emodin/LPS cotreatmented rat livers samples. These results indicate that non-toxic dosage of LPS potentiates the hepatotoxicity of emodin. This discovery raises the possibility that emodin and herbal medicines containing it may induce liver injury in the inflammatory stress even in their therapeutic dosages.

Antioxidant and Hepatoprotective Potentiality of Randia dumetorum Lam. Leaf and Bark via Inhibition of Oxidative Stress and Inflammatory Cytokines

“…Serum enzyme levels are significant markers to determine the severity of damage to particular tissue ( Tu et al, 2015 ). CCl 4 administration cause significant increase in serum enzyme levels like AST, ALT, ALP, LDH, Albumin and decrease levels of total protein levels when compared with control animals which indicate the liver damage.…”

Polygonum multiflorum-Induced Liver Injury: Clinical Characteristics, Risk Factors, Material Basis, Action Mechanism and Current Challenges

“…An analysis of the correlation between PM compounds and cytotoxicity revealed that 10 compounds may be related to the hepatotoxicity of PM, 7 of which are guanidine or glucoside compounds . Hepatotoxicity could be induced by emodin at high, medium and low doses, indicating that the anthraquinones may be the basis of potential hepatotoxic effects of PM (Can et al, 2015). Studies have demonstrated obvious hepatotoxicities of emodin and rhein.…”

Molecular Mechanisms Involved in Oxidative Stress-Associated Liver Injury Induced by Chinese Herbal Medicine: An Experimental Evidence-Based Literature Review and Network Pharmacology Study

“…In contrast to the therapeutic effects, side effects of TCM, such as hepatotoxicity, have rarely been reported. However, accumulating evidence regarding TCM-associated oxidative hepatotoxicity was frequently addressed in recent years, particularly in paradoxical pharmacological activities of toxic and curative actions [ 12 ]. The most vital clue is the association between the initiation of TCM administration and hepatotoxicity generation and, of equal importance, to the deceleration following withdrawal.…”