There are numerous studies to indicate that irradiation induces reactive oxygen species (ROS), which play an important causative role in radiation damage of the cell. We evaluated the effects of ginsan, a polysaccharide fraction extracted from Panax ginseng, on the γ-radiation induced alterations of some antioxidant systems in the spleen of Balb/c mice. On the 5th day after sublethal whole-body irradiation, homogenized spleen tissues of the irradiated mice expressed only marginally increased mRNA levels of Mn-SOD (superoxide dimutase) in contrast to Cu/Zn-SOD, however, catalase mRNA was decreased by ∼50% of the control. In vivo treatment of non-irradiated mice with ginsan (100 mg kg−1, intraperitoneal administration) had no significant effect, except for glutathione peroxidase (GPx) mRNA, which increased to 144% from the control. However, the combination of irradiation with ginsan effectively increased the SODs and GPx transcription as well as their protein expressions and enzyme activities. In addition, the expression of heme oxygenase-1 and non-protein thiol induced by irradiation was normalized by the treatment of ginsan. Evidence indicated that transforming growth factor-β and other important cytokines such as IL-1, TNF and IFN-γ might be involved in evoking the antioxidant enzymes. Therefore, we propose that the modulation of antioxidant enzymes by ginsan was partly responsible for protecting the animal from radiation, and could be applied as a therapeutic remedy for various ROS-related diseases.

Ginsan, a polysaccharide isolated from Panax ginseng, has been shown to be a potent immunomodulator, producing a variety of cytokines such as TNF-alpha, IL-1, IL-2, IL-6, IL-12, IFN-gamma and GM-CSF, and stimulating lymphoid cells to proliferate. In the present study, we analyzed some immune functions 1st-5th days after ginsan i.p. injection, including the level of non-protein thiols (NPSH) as antioxidants, heme oxygenase (HO) activity as a marker of oxidative stress, zoxazolamine-induced paralysis time and level of hepatic cytochrome P-450 (CYP450) as indices of drug metabolism system, and activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, and albumin level as indicators of hepatotoxicity. Ginsan in the dose of 100 mg/kg caused marked elevation (1.7 to approximately 2 fold) of HO activity, decrease of total CYP450 level (by 20-34%), and prolongation of zoxazolamine-induced paralysis time (by 65-70%), and showed some differences between male and female mice. Ginsan treatment did not seem to cause hepatic injury, since serum AST, ALT, and ALP activities and levels of total bilirubin and albumin were not changed.

Ionizing radiation produces reactive oxygen species, which exert diverse biological effects on cells and animals. We investigated alterations of heme oxygenase (HO) and non-protein thiols (NPSH), which are known as two major anti-oxidant enzymes, in female and male C57BL/6 mice in the lung, liver, and brain after whole-body γ-irradiation with 10 Gy (1-7 days) as well as in the lung after whole-thorax γ-irradiation (WTI) with 12.5 Gy (1-26 weeks). Most significant alteration of HO activity was observed in the liver, which elevated 250% in males. NPSH level in female liver was increased on the 5th-7th days but decreased in males on the 3rd day. In the lung, the elevation of HO activity in both sexes and the pattern of NPSH change were similar to that of the liver. On the other hand, the increase of HO activity on the 16th week and the decrease of NPSH level on the 2nd week were observed only in male lung after WTI. This study shows that the liver is the most sensitive tissue to γ-irradiation-induced alterations of HO activity in both female and male mice. In addition, there exists significant differential effect of γ-irradiation on anti-oxidant system in female and male mice.

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