Preserving GSH/GSSG ratio can happen by either increasing GSH biosynthesis or activating GSH-recycle enzyme (GR) activity [22]. In this study, increased GR activity in Rg1-treated exercised rats may contribute to the preservation of GSH/GSSG ratio. Red ginseng see more extract has been shown to elevate Quisinostat in vitro the rate-limiting enzyme of GSH-biosynthesis and protect the cells from oxidative cell death [23]. Furthermore, pretreatment of protopanaxatriol containing Rg1 has been reported to boost the GR activity and maintain the stable GSH/GSSG ratio against H2O2-induced oxidative stress in endothelial cells [24]. Therefore, Rg1 may be the active

component of protopanaxatriol that accounts for stabilization of GSH/GSSG ratio against various types of external challenges. Furthermore, GST acts to conjugate peroxidized lipids to GSH [22]. In our study, muscle GST activity was not affected by exhaustive exercise, which agreed with the results reported by Malaguti et al. [25]. Yet, muscle GST activity was increased in Rg1 pre-treatment rats which may partly contribute to the attenuated lipid

peroxidation after exercise. Endogenous free radicals are removed by a set of antioxidant enzymes, including SOD, CAT, and GPx. Previous studies have shown increased [26], decreased [27] or no change [28] in SOD activity after exhaustive exercise. Our data showed AG-881 mw marginally decreased SOD activity after exhaustive exercise in control group. Furthermore, CAT and GPx works in decomposing the toxic H2O2 to water and oxygen. Here, both CAT and GPx activities showed similar response after long-term Rg1 supplementation and acute exercise. Increases in CAT and GPx in exercised rats are noted as a compensatory response against excessive H2O2 levels [29, 30]. However, Taysi et al. [31] reported decreased liver CAT activity after exhaustive treadmill running. This discrepancy might be due to tissue specific response or mode of exercise.

Increased GPx activity was similar with the findings by Caillaud et al. [28], who reported increased muscle GPx activity after exercise. Ginseng saponins have been IKBKE shown to increase CAT gene expression and protect the liver from thioacetamide-induced injury [32]. Voces et al. [33] reported improved liver antioxidant status along with GPx activity by ginseng extracts. Rg1 supplementation also increased CAT and GPx activities in non-exercise rats, which may explain, in part, the enhanced antioxidant defense system by ginseng. Conclusion The results of the study provide strong evidence that long-term Rg1 supplementation can effectively attenuate the exhaustive exercise-induced increased lipid peroxidation and decreased GSH/GSSG ratio in rat skeletal muscle. The beneficial effect of Rg1 is also explained, in part, by the steady state maintenance of antioxidant defense system in the skeletal muscle.