Gang Xu1,2,3, Yi-Kun Shi1,2,3, Bin-Da Sun1,2,3, Lu Liu1,2,3, Guo-Ji E1,2,3, Shu He1,2,3, Jian-Yang Zhang1,2,3, Bao Liu1,2,3, Qiu Hu1,2,3, Jian Chen1,2,3, Yu-Qi Gao4,5,6, Er-Long Zhang7,8,9. 1. Institute of Medicine and Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University, Number 30, Gaotanyan Street, District of Shapingba, Chongqing, 400038, China. 2. Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, China. 3. Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China. 4. Institute of Medicine and Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University, Number 30, Gaotanyan Street, District of Shapingba, Chongqing, 400038, China. gaoy66@yahoo.com. 5. Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, China. gaoy66@yahoo.com. 6. Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China. gaoy66@yahoo.com. 7. Institute of Medicine and Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University, Number 30, Gaotanyan Street, District of Shapingba, Chongqing, 400038, China. loong0810@sina.com. 8. Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, China. loong0810@sina.com. 9. Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China. loong0810@sina.com.
Abstract
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.
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.
Entities:
Keywords:
DL-3-n-butylphthalide; Energy metabolism; Hypobaric hypoxia; Learning and memory function; Oxidative stress; Physical function
Authors: Eya Qaid; R Zakaria; S F Sulaiman; Na Mohd Yusof; N Shafin; Z Othman; A H Ahmad; Cb Abd Aziz Journal: Hum Exp Toxicol Date: 2017-01-23 Impact factor: 2.903