Puerarin attenuates cadmium-induced hepatic lipid metabolism disorder by inhibiting oxidative stress and inflammation in mice.

Cadmium (Cd) is a common environmental pollutant with known toxic effects on the liver. Puerarin (PU), a natural flavonoid, has been shown to exert protective effect in numerous pathological processes. However, whether PU affords protection in Cd-induced liver damage is still equivocal. Therefore, 40 mice were treated with Cd and/or PU by gavage for 9 weeks, then the serum and liver samples were collected to verify this issue. In this study, Cd exposure triggered hepatic lipid metabolism disorders and resultant liver damage as evidenced by Oil Red O staining and total cholesterol (TC) and triglyceride (TG) levels in serum and liver, aspartate transaminase (AST) and alanine transaminase (ALT) levels in serum, and histopathology, which were significantly improved by PU. Moreover, PU also normalized the expression of Cd-disturbed lipid metabolism-related proteins to improve lipid accumulation, contributing to the alleviation of liver injury. Moreover, Cd-decreased antioxidative indices superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) as well as glutathione (GSH) in hepatic tissues were significantly attenuated by PU administration, while Cd-elevated hepatic malondialdehyde (MDA) and reactive oxygen species (ROS) levels were markedly down-regulated by PU treatment, demonstrating the antioxidant effect of PU against Cd exposure. In addition, PU supplementation increased the anti-inflammatory potential, and normalized the levels of proinflammatory cytokines during Cd exposure. In conclusion, these observations demonstrate that PU treatment decreases oxidative stress and inflammation response, which may contribute to prevent Cd-induced lipid metabolism disorder and consequent liver damage.

Wan XM ，Chen J ，Wang M ，Zheng C ，Zhou XL ... -  《-》

Protective effect of eugenol on hepatic inflammation and oxidative stress induced by cadmium in male rats.

Cadmium is one of the most toxic heavy metals. The prolonged exposure of it can lead to severe alterations and damage in different tissues including blood, liver, kidney and brain. Eugenol, a phenolic compound, is present in various aromatic plants. It acts as a natural antioxidant and anti-inflammatory agent. The aim of this study was to investigate whether the treatment of eugenol is beneficial against the hepatic oxidative stress and inflammation induced by Cd. To study the effect of eugenol in reversal of Cd toxicity, 24 albino rats were equally divided into four different groups: G1 Control (saline), G2 Eugenol (3 mg kg-1), G3 CdCl2 (5 mg kg-1) and G4 CdCl2 + Eugenol (5 mg kg-1 + 3 mg kg-1). All the groups were treated with gavage orally for the period of 21 days. After this treatment period, rats were sacrificed and liver tissues were removed. The hepatic antioxidant status was evaluated by measuring the activities of SOD, Catalase and GST enzymes. The reduced glutathione, lipid peroxidation, protein carbonyl oxidation (PCO) and thiol contents were measured in hepatic tissues. The activities of liver marker enzymes such as ALT, AST, GGT, ALP, TP, albumin, Bilirubin content and LDH were determined to assess the hepatic damage in different groups. Cd induced hepatic inflammation was determined by evaluating the levels of TNF-a, IL-6 and NO. Oral intoxication of Cd for 21 days significantly elevated the level of hepatic markers including activities of LDH, GGT, ALP, ALT, AST and Bilirubin level. The albumin content, reduced GSH level, and activities of antioxidant enzymes were significantly reduced in Cd treated group. The levels of inflammatory markers were significantly elevated in Cd treated group. The eugenol treatment was very effective and it significantly reversed the Cd induced biochemical alterations almost similar to that of control. The results demonstrated that the eugenol possessed very strong anti-oxidative and anti-inflammatory potential. The co-treatment of eugenol with Cd exhibited protective potential of eugenol against Cd induced toxicity. Eugenol was able to improve the cellular redox system in rats treated with Cd.

Kumar A ，Siddiqi NJ ，Alrashood ST ，Khan HA ，Dubey A ，Sharma B ... -  《-》

Puerarin prevents cadmium-induced hepatic cell damage by suppressing apoptosis and restoring autophagic flux.

Cadmium (Cd) is a common heavy metal contamination that is highly toxic to liver. Puerarin (PU), a potent free radical scavenger, has been shown to exert cytoprotective effect in numerous pathological processes. However, whether PU affords protection against Cd-induced hepatotoxicity remains unclear to be known. Here, we aimed to investigate the protective effect of PU on Cd-induced hepatotoxicity in an immortalized mouse hepatocyte line, AML-12. First, Cd-induced cytotoxicity in AML-12 cells was obviously ameliorated by PU treatment. Also, Cd-induced apoptotic cell death was markedly alleviated by PU treatment, evidenced by two methods. Simultaneously, Cd-elevated malondialdehyde and reactive oxygen species levels were significantly reduced by PU administration, demonstrating the antioxidant effect of PU against Cd exposure. Moreover, Cd-induced blockage of autophagic flux in AML-12 cells was obviously restored by PU treatment, evidenced by immunoblot analysis of autophagy marker proteins and tandem fluorescent-tagged LC3 method. Resultantly, Cd-induced autophagosome accumulation was significantly alleviated by PU treatment. In conclusion, these observations demonstrate that PU treatment alleviates Cd-induced hepatic cell damage by inhibiting apoptosis and restoring autophagy activity, which is intimately related with its antioxidant activity.

Zhou XL ，Wan XM ，Fu XX ，Xie CG ... -  《-》

Influence of ferulic acid consumption in ameliorating the cadmium-induced liver and renal oxidative damage in rats.

Sanjeev S ，Bidanchi RM ，Murthy MK ，Gurusubramanian G ，Roy VK ... -  《-》

Cadmium-induced hepatotoxicity in rats and the protective effect of naringenin.

This experiment pertains to the protective role of naringenin against cadmium (Cd)-induced oxidative stress in the liver of rats. Cadmium is a major environmental pollutant and is known for its wide toxic manifestations. Naringenin is a naturally occurring citrus flavonone which has been reported to have a wide range of pharmacological properties. In the present investigation cadmium (5mg/kg) was administered orally for 4 weeks to induce hepatotoxicity. Liver damage induced by cadmium was clearly shown by the increased activities of serum hepatic marker enzymes namely aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma glutamyl transferase (GGT) and serum total bilirubin (TB) along with the increased level of lipid peroxidation indices (thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides) and protein carbonyl contents in liver. The toxic effect of cadmium was also indicated by significantly decreased levels of enzymatic antioxidants (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST)) and non-enzymatic antioxidants (reduced glutathione (GSH), vitamin C and vitamin E). Administration of naringenin at a dose of (50mg/kg) significantly reversed the activities of serum hepatic marker enzymes to their near-normal levels when compared to Cd-treated rats. In addition, naringenin significantly reduced lipid peroxidation and restored the levels of antioxidant defense in the liver. The histopathological studies in the liver of rats also showed that naringenin (50mg/kg) markedly reduced the toxicity of cadmium and preserved the normal histological architecture of the tissue. The present study suggested that naringenin may be beneficial in ameliorating the cadmium-induced oxidative damage in the liver of rats.

Renugadevi J ，Prabu SM 《-》