Abstract: This study explored the anti-fatigue effect of glutathione (GSH) in mice and its underlying mechanisms. Mice were randomly divided into normal control, exercise-induced fatigue, GSH treatment and American ginseng (AG) control groups. The mice in the treatment groups were intragastrically administered with GSH (0.2, 0.4 and 0.8 g/kg mb) and AG (0.6 g/kg mb) daily before exercise, respectively, while the mice in the remaining groups were given normal saline. The experiment lasted for 10 days. The mice were sacrificed immediately after exhaustive swimming on the last day of the experiment to determine biochemical markers. The number of c-fos positive cells in the paraventricular nucleus (PVN) of the hypothalamus was measured by immunohistochemically. Compared with exercise-induced fatigue group, both GSH and AG significantly prolonged exhaustive swimming time (P < 0.05). Furthermore, the levels of blood lactic acid (LAC), lactic dehydrogenase (LDH) activity, blood urea nitrogen (BUN) and creatine phosphokinase (CK) activity in serum as well as malondialdehyde (MDA) content in liver decreased significantly (P < 0.05), while glycogen content and superoxide dismutase (SOD) activity in liver significantly increased in the GSH-treated mice (P < 0.05). With regard to central fatigue, GSH significantly increased dopamine (DA) content (P < 0.05), and decreased 5-hydroxytryptamine (5-HT) content in the hypothalamus and induced the over-expression of c-fos positive cells in the PVN. While the anti-fatigue effect of high-dose GSH was not significantly different from that of AG (P > 0.05), GSH had obvious anti-fatigue effect in mice via peripheral and central mechanisms, and could be used as a drug candidate for relieving exercise-induced fatigue.

Key words: glutathione, anti-fatigue, paraventricular nucleus, c-fos positive cells, exhaustive swimming test