Protective Effect of Korean Red Ginseng against Aflatoxin B1-Induced Hepatotoxicity in Rat

Abstract

Korean red ginseng (KRG), the steamed root of Panax ginseng Meyer, has a variety of biological properties, including anti-inflammatory, antioxidant and anticancer effects. Aflatoxin B1 (AFB1) produced by the Aspergillus spp. causes acute hepatotoxicity by lipid peroxidation and oxidative DNA damage, and induces liver carcinoma in humans and laboratory animals. This study was performed to examine the protective effects of KRG against hepatotoxicity induced by AFB1 using liver-specific serum marker analysis, histopathology, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. In addition, to elucidate the possible mechanism of hepatoprotective effects, superoxide dismutase, catalase, glutathione peroxidase, and malondialdehyde were analyzed. Rats were treated with 250 mg/kg of KRG (KRG group) or saline (AFB1 group) for 4 weeks and then received 150 μg/kg of AFB1 intraperitoneally for 3 days. Rats were sacrificed at 12 h, 24 h, 48 h, 72 h, or 1 wk after AFB1 treatment. In the KRG pre-treatment group, serum alanine aminotransferase, aspartate aminotransferase, and malondialdehyde levels were low, but superoxide dismutase, catalase, and glutathione peroxidase activities were high as compared to the AFB1 alone group. Histopathologically, AFB1 treatment induced necrosis and apoptosis in hepatocytes, and led to inflammatory cells infiltration in the liver. KRG pre-treatment ameliorated these changes. These results indicate that KRG may have protective effects against hepatotoxicity induced by AFB1 that involve the antioxidant properties of KRG.

Keywords: Aflatoxin B1; Antioxidant enzymes; Korean red ginseng; Panax ginseng.

Fig. 1.. Liver specific serum biomarker analysis in rats treated with Aflatoxin B₁ (AFB₁) with or without Korean red ginseng (KRG). Serum alanine aminotransferase (A) and aspartate aminotransferase (B) were relatively low in group pretreated with KRG compared to the group treated only with AFB₁.

Fig. 2.. Representative photomicrograph of liver lesions in rats treated with Aflatoxin B₁ (AFB₁) with or without Korean red ginseng (KRG) pretreatment. H&E stain. (A,B) Centrilobular (CV) and periportal (PT) zone of the control group. Bar=50 μm. (C) Hepatic lesion found in the AFB₁-treated group after 12 h; severe necrosis of hepatocytes and loss of hepatic cords were observed around the portal region. Bar=100 μm. (D) Higher magnification of (C). Severe hepatocyte necrosis was noted around the portal triad. Bar=50 μm. (E) Hepatic lesions of the KRG pretreated group after 12 h; mild necrosis in hepatocytes and loss of hepatic cords were observed around the portal region. Bar=100 μm. (F) Higher magnification of (E). Mild hepatocyte necrosis was noted around the portal triad. Bar=50 μm.

Fig. 3.. Apoptosis in liver of rats treated with Aflatoxin B₁ (AFB₁) with or without Korean red ginseng (KRG) pretreatment. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) stain. Bar=50 μm. (A) Control group; few TUNEL-labeled apoptotic cells (arrow) were noted. (B) AFB₁ group; at 12 h many apoptotic cells were observed. (C) KRG pretreated group; at 12 h the number of apoptotic cells decreased compared to the AFB₁ group. (D) AFB₁ group; at 48 h the number of apoptotic cells decreased. CV, central vein; PT, portal triad.

Fig. 4.. Level of hepatic antioxidant enzymes in rats treated with Aflatoxin B₁ (AFB₁) with or without Korean red ginseng (KRG) pretreatment. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) enzyme activity was increased after 12 h in the KRG and AFB₁ groups compared to the control group. These enzyme activities were relatively higher in the KRG group compared to the AFB₁ group.

Fig. 5.. The levels of malondialdehyde (MDA), a natural byproduct of lipid peroxidation, in the plasma and liver of rats treated with Aflatoxin B₁ (AFB₁) with or without Korean red ginseng (KRG) pretreatment. Plasma MDA levels were higher in the AFB₁ group compared to the control and KRG group at each time point except at 72 h. In addition, MDA levels in the liver were higher in the AFB₁ group than the control and KRG groups at 12 and 24 h. *Significantly different from the control and KRG group.