Background Studies have revealed the protective effect of DL-3-n-butylphthalide (NBP) against diseases associated with ischemic hypoxia. However, the role of NBP in animals with hypobaric hypoxia has not been elucidated. This study investigated the effects of NBP on rodents with acute and chronic hypobaric hypoxia. Methods Sprague-Dwaley rats and Kunming mice administered with NBP (0, 60, 120, and 240 mg/kg for rats and 0, 90, 180, and 360 mg/kg for mice) were placed in a hypobaric hypoxia chamber at 10,000 m and the survival percentages at 30 min were determined. Then, the time and distance to exhaustion of drug-treated rodents were evaluated during treadmill running and motor-driven wheel-track treadmill experiments, conducted at 5800 m for 3 days or 20 days, to evaluate changes in physical functions. The frequency of active escapes and duration of active escapes were also determined for rats in a shuttle-box experiment, conducted at 5800 m for 6 days or 27 days, to evaluate changes in learning and memory function. ATP levels were measured in the gastrocnemius muscle and malonaldehyde (MDA), superoxide dismutase (SOD), hydrogen peroxide (H2O2), glutathione peroxidase (GSH-Px), and lactate were detected in sera of rats, and routine blood tests were also performed. Results Survival analysis at 10,000 m indicated NBP could improve hypoxia tolerance ability. The time and distance to exhaustion for mice (NBP, 90 mg/kg) and time to exhaustion for rats (NBP, 120 and 240 mg/kg) significantly increased under conditions of acute hypoxia compared with control group. NBP treatment also significantly increased the time to exhaustion for rats when exposed to chronic hypoxia. Moreover, 240 mg/kg NBP significantly increased the frequency of active escapes under conditions of acute hypoxia. Furthermore, the levels of MDA and H2O2 decreased but those of SOD and GSH-Px in the sera of rats increased under conditions of acute and chronic hypoxia. Additionally, ATP levels in the gastrocnemius muscle significantly increased, while lactate levels in sera significantly decreased. Conclusion NBP improved physical and learning and memory functions in rodents exposed to acute or chronic hypobaric hypoxia by increasing their anti-oxidative capacity and energy supply.

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Abstract Background: Studies revealed the protective effect of DL-3-n-butylphthalide (NBP) against ischemic hypoxia diseases. However, the role of NBP in animals with hypobaric hypoxia is elusive. This study investigated the effect of NBP on animals with acute and chronic hypobaric hypoxia.Methods: SD rats and Kunming mice administrated with NBP (90, 180 and 360 mg/kg for mice, and 60, 120, and 240 mg/kg for rats) were located in 10,000 m hypobaric hypoxia chamber. And survival analysis of animals implied that NBP could significantly improve survival percent at 30 min. Then, treated animals were evaluated for exhaustive time and exhaustive distance in forced exercise wheel-track treadmill and treadmill running experiments at 5,800 m for 3 or 21 days, to evaluate physical functions. Rats were also evaluated for times of active escape, average time of active escape, time of passive escape, and average time of passive escape in a shuttle-box experiment at 5,800 m for 7 or 28 days, to evaluate cognitive functions. ATP level was evaluated in the gastrocnemius muscle and maloaldehyde (MDA), superoxide dismutase (SOD), hydrogen peroxide (H2O2), lactate, and glutathione peroxiase (GSH-Px) measurements and routine blood tests were detected.Results: Exhaustive time for rats (NBP, 120 and 240 mg/kg) and exhaustive time and distance for mice (NBP, 90 mg/kg) significantly increased under acute hypoxia. And NBP treatment significantly increased the exhaustive time for rats under chronic hypoxia. Moreover, NBP of 120 and 240 mg/kg significantly increased the average time of passive escape under acute and chronic hypoxia. These results suggested that NBP could improve physical and cognitive functions under acute and chronic hypobaric hypoxia. Furthermore, the levels of MDA and H2O2 decreased but those of SOD and GSH-Px increased under acute and chronic hypoxia. Furthermore, the content of ATP significantly increased, while lactate level significantly decreased. The results presented that NBP could regulate redox homeostasis and improve energy metabolism.Conclusion: NBP could improve physical and cognitive functions under acute and chronic hypobaric hypoxia by increasing anti-oxidative capacity and energy supply.