Comparative Assessment of the Effectiveness of HSP70 / HIF-1α System Modulators after Prenatal Hypoxia

Olena Aliyeva^1*, Igor Belenichev², Nina Bukhtiyarova³, Denis Semenov⁴ and Sergiy Voloshchuk⁵

¹Department of Histology, Cytology, and Embryology, Zaporizhzhia State Medical and Pharmaceutical University, Zaporizhzhia, Ukraine.

²Department of Pharmacology and Medical Formulation with Course of Normal Physiology, Zaporizhzhia State Medical and Pharmaceutical University, Zaporizhzhia, Ukraine.

³Department of Clinical Laboratory Diagnostics, Zaporizhzhia State Medical and Pharmaceutical University, Zaporizhzhia, Ukraine.

⁴Department of Surgical and Propaedeutic Dentistry, Zaporizhzhia State Medical and Pharmaceutical University, Zaporizhzhia, Ukraine.

⁵Department of Neurology and neurosurgery of postgraduate education faculty, National Pirogov Memorial Medical University, Vinnytsya, Ukraine.

Corresponding Author E-mail: aliyeva1eg@gmail.com

Abstract: Prenatal hypoxia (PH) poses a significant threat to fetal development and may be responsible for neonatal mortality or neurodevelopmental abnormalities. The proteins HSP70 and HIF-1, which hold a distinct significance in the cellular reaction to PH, can be regarded as potential targets for pharmaceutical interventions aimed at mitigating the repercussions of chronic PH. This study aimed to identify a possible correlation between offspring survival and stages of expression of endogenous neuroprotective factors (HSP70 and HIF-1) after chronic prenatal hypoxia with course administration of potential HSP70 modulators (angiolin, piracetam, thiotriazoline, nicomex, cerebrocurin, tamoxifen, L-arginine, glutoredoxin, HSF-1, and mildronate). In the rat offspring after PH we determined the plasma concentrations of HSP70 and HIF-1 by solid-phase ELISA immunoassay, and the expression of HIF-1 mRNA and HSP70 mRNA by real-time PCR. For the first time, we found a positive correlation between offspring survival after PH and the expression of HIF-1 and HSP70, both in groups without experimental therapy and in groups receiving pharmacological agents. The course administration of HSP70/HIF-1α modulators, especially angiolin (50 mg/kg), cerebrocurin (150 mg/kg), and HSF-1 (50 mg/kg), to rats that underwent PH reduces postnatal lethality, increases blood plasma concentrations of HSP70 and HIF-1α, and positively affects the expression level of HIF-1α mRNA in the rat brain. These drugs can be considered as the most promising drug candidates for new therapeutic strategies of pharmacological correction of the consequences of chronic PH.

Keywords: Central nervous system; HIF-1; HSP70; neuroprotection; pharmacological correction; prenatal hypoxia

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