American Ginseng Modifies Cs-Induced DNA Damage and Oxidative Stress in Human Lymphocytes

Abstract

The multifold bioactive medicinal properties of ginseng have been closely linked to its antioxidative ability, which is related to its ginsenoside content. Since the key mechanism of radiation-induced cell death and tissue damage is the generation of reactive oxygen species (ROS) that attack cellular DNA, this study focuses on the impact of a standardized North American ginseng extract (NAGE) on (137)Cs-induced oxidative stress in human peripheral lymphocytes (PBL) obtained from 10 healthy individuals (6M/4F), 42.7 +/- 4.6 years of age. At two different time points (0 h and 24 h before irradiation), we applied NAGE (250 - 1000 microg ml(-1)) to mononuclear cell cultures for cytokinesis-block micronuclei (MN) assay and determination of the state of oxidative stress in PBL. We found that at both time points, NAGE significantly reduced the MN yields in PBL after irradiation (1 and 2 Gy) in a concentration-dependent manner (P<0.001). Compared with radiation alone, the maximum reduction rate of MN yield were 51.1% and 49.1% after 1 Gy and 2 Gy exposures, respectively. We also found that before irradiation the presence of NAGE in the culture medium resulted in a significant increased intracellular total antioxidant capacity (TAC) in PBL. At both time points, the increment of (137)Cs-induced MN yields in PBL was positively correlated with the increment of intracellular ROS production (R = 0.6 - 0.7, P = 0.002), but negatively correlated with the reduction of TAC levels (R = -0.4 -0.5, P = 0.02 - 0.004). However, the presence of NAGE in the culture medium significantly increased the TAC levels, while concomitantly decreasing both ROS production and MN yields in PBL (P<0.001). Our findings that NAGE is effective in protecting human PBL against radiation-induced oxidative stress should encourage further in vivo study of dietary supplementation with NAGE as an effective natural radiation countermeasure.

Fig. 1

Effect of NAGE (ug ml⁻¹) applied at 0 h (Time 1) on (A) ¹³⁷Cs-induced MN yields in PBL; (B) intracellular TAC levels (mM Trolox Eq./L) in PBL before and after ¹³⁷Cs irradiation; and (C) intracellular ROS levels (% of control) in PBL before and after ¹³⁷Cs irradiation. Each bar represents the mean ± SEM of duplicate independent measurements pooled from each individual compared to their respective irradiated controls (*P<0.001, •P<0.02).

Fig. 2

Effect of NAGE (ug ml⁻) applied at 24 h before irradiation (Time 2) on (A) ¹³⁷Cs-induced MN yields in PBL; (B) intracellular TAC levels (mM Trolox Eq./L) in PBL before and after ¹³⁷Cs irradiation; and (C) intracellular ROS levels (% of control) in PBL before and after ¹³⁷Cs irradiation. Each bar represents the mean ± SEM of duplicate independent measurements pooled from each individual compared to their respective irradiated controls (*P<0.001, •P<0.02, #P<0.01, †P<0.05).

Fig. 3

Correlation between IR-induced MN yields and intracellular (A) TAC levels (mM Trolox Eq./L, R = −0.5, P= 0.004) and (B) ROS levels (% of control, R = 0.6, P = 0.002) in PBL with the presence of NAGE at different concentrations applied at 0 h (Time 1).

Fig. 4

Correlation between IR-induced MN yields and intracellular (A) TAC levels (mM Trolox Eq./L, R = −0.43, P = 0.02) and (B) ROS levels (% of control, R = 0.70, P = 0.002) in PBL with the presence of NAGE at different concentrations applied at 24 h before ¹³⁷Cs irradiation (Time 2).