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[Effect of neotype carbonic anhydrase target-based inhibitors(P-8) on the hypoxic tolerance in mice]
Yu-gang Shu1, Dong-xiang Zhang, Zhong-hai Xiao
1Key Laboratory of Miltary Enviromental Medicine Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Tianjin 300050, China.
Objective:
To explore the effects of different doses of P-8 in increasing the Hypoxia tolerance of mice and the mechanisms involved.
Methods:
The health mice were placed into the oxygen deficit bottles and measured the survival time in the condition of hypoxia. The male mice were put into the ladder cage, then placed them into the hypobaric champer to determine the survival time of mice with decompression hypoxia (min). We observed the activity changes of the mice's organization carbonic anhydrase II (CAII). By using the drug in prophylaxis, we investigated the effects of carbonic anhydrase target-based inhibitors P-8 for improving the hypoxia tolerance.
Results:
(1) In improving the endurance of mice in the condition of hypoxia, the survival time of 6.25 mg/(kg x d) and more doses of P-8 groups were (27.38 +/- 4.63, 29.53 +/- 4.43, 29.67 +/- 7.28, 31.55 +/- 6.34, 32.45 +/- 6.65, 36.81 +/- 7.24 and 35.41 +/- 4.20) min, compared with the control group (22.90 +/- 3.19) min , the survival time significantly prolonged (P < 0.05, P < 0.01); compared to the same dose of acetazolamide groups (24.54 +/- 3.17, 22.70 +/- 3.04, 22.67 +/- 2.99, 23.93 +/- 0.96, 27.87 +/- 5.06, 30.79 +/- 5.12 and 35.14 +/- 6.46) min, the survival time significantly prolonged; P-8 groups and Acetazolamide's minimum effective dose were 6.25 and 100 mg/(kg x d), the potency of P-8 is 16 times Acetazolamide. (2) In improving the endurance of mice in the condition of hypoxia, the survival time of middle and high doses of P-8 groups [(24.82 +/- -3.92, 28.27 +/- 5.89) min] were significantly longer than those in control group [(21.96 2.51) min, P < 0.05]; compared with the acetazolamide (23.11 +/- 3.71) min, the survival time of high dose of P-8 group was significantly prolonged. (3) Compared with the normal control group, P-8 [(25 mg/(kg x d), 50 mg/(kg x d), 100 mg/(kg x d), 200 mg/(kg x d)] dose groups inhibited the activity of carbonic anhydrase II (CAII) in the renal (P < 0.05, P < 0.01); P-8 [100 mg/(kg x d) and 200 mg/(kg x d)] dose group significantly inhibited the activity of carbonic anhydrase II (CA II) in the brain (P < 0.05).
Conclusion:
P-8 treatment improved the endurance of mice in the condition of hypoxia and worked better than Acetazolamide. The mechanism may be related to the inhibition of carbonic anhydrase organization.
Insights
P-8 significantly enhanced hypoxia tolerance in mice, outperforming Acetazolamide. This compound may improve endurance by inhibiting carbonic anhydrase activity.
Area of Science:
- Physiology
- Pharmacology
Background:
- Hypoxia poses a significant challenge to physiological function.
- Carbonic anhydrase II (CAII) plays a role in cellular response to oxygen deprivation.
Purpose of the Study:
- To evaluate the efficacy of P-8 in improving hypoxia tolerance in mice.
- To elucidate the underlying mechanisms of P-8's effects on hypoxia.
Main Methods:
- Mice were exposed to hypoxic conditions to measure survival time.
- The activity of carbonic anhydrase II (CAII) was assessed in various tissues.
- P-8 was administered to investigate its prophylactic effects against hypoxia.
Main Results:
- P-8 administration significantly prolonged survival time under hypoxia in a dose-dependent manner.
- P-8 demonstrated superior efficacy compared to Acetazolamide, with a minimum effective dose 16 times lower.
- P-8 inhibited CAII activity in renal and brain tissues at effective doses.
Conclusions:
- P-8 effectively improves hypoxia tolerance in mice.
- The mechanism involves the inhibition of carbonic anhydrase activity.
- P-8 represents a promising therapeutic agent for hypoxia-related conditions.
