Effect of HIF-1α inhibition with topotecan and postconditioning on cardiac and skeletal muscle biomarkers during severe hypoxia

Abstract

The work used a model of severe hypobaric hypoxia (SH) – a three-hour session of rats staying at 180 mmHg (5% O2) and an attempt was made to evaluate the possibility of its use for muscle tissue by determining biomarkers of cardiac muscle and skeletal muscles damage in the blood plasma. To assess the effect of HIF1, we used the HIF-1α translation inhibitor, topotecan, which was administered intraperitoneally (5 mg/kg body weight) in a DMSO–0.09% NaCl mixture 10 min before hypoxia. For postconditioning (PostC), moderate hypobaric hypoxia was used [1]. A significant increase in the level of cardiac biomarker troponin I in the blood plasma of rats subjected to TH was shown, which indicated myocardial damage after SH. The blood level of the nonspecific muscle biomarker myoglobin did not change significantly after SH. However, when the HIF-1α inhibitor topotecan was used before SH, the amount of myoglobin in the blood plasma of rats one day after the SH session was significantly lower than in the absence of the inhibitor. Thus, it can be assumed that inhibition of the transcription factor HIF-1α before SH reduces skeletal muscle damage. Topotecan can be proposed as a means to reduce damage to injured muscles.

Keywords

• hypoxia
• myoglobin
• troponin i
• topotecan
• hypoxia-inducible factor hif-1α
• postconditioning
• biomarkers for muscle damage