Changes in attachment and metabolic activity of rat neonatal cardiomyocytes and nonmyocytes caused by Macrovipera lebetina obtusa venom

Hovhannes Arestakesyan, Orbeli Institute of Physiology, National Academy of Sciences, 22 Orbeli Bros. St., Yerevan 0028, Armenia; Department of Pharmacology and Physiology, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037, USA.
Narine LeFevre, Department of Pharmacology and Physiology, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037, USA.
Nikki Posnack, Department of Pharmacology and Physiology, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037, USA; Children's National Heart Institute, Sheikh Zayed Institute of Pediatric Surgical Innovation, Washington, DC 20010, USA.
Arni Sarian, Orbeli Institute of Physiology, National Academy of Sciences, 22 Orbeli Bros. St., Yerevan 0028, Armenia.
Vahan Grigoryan, Orbeli Institute of Physiology, National Academy of Sciences, 22 Orbeli Bros. St., Yerevan 0028, Armenia.
Naira Ayvazyan, Orbeli Institute of Physiology, National Academy of Sciences, 22 Orbeli Bros. St., Yerevan 0028, Armenia.
Armen Voskanyan, Orbeli Institute of Physiology, National Academy of Sciences, 22 Orbeli Bros. St., Yerevan 0028, Armenia.
Narine Sarvazyan, Orbeli Institute of Physiology, National Academy of Sciences, 22 Orbeli Bros. St., Yerevan 0028, Armenia; Department of Pharmacology and Physiology, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037, USA.
Zaruhi Karabekian, Orbeli Institute of Physiology, National Academy of Sciences, 22 Orbeli Bros. St., Yerevan 0028, Armenia; Department of Pharmacology and Physiology, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037, USA. Electronic address: zkarabekian@physiol.sci.am.

Document Type

Journal Article

Publication Date

12-6-2023

Journal

Toxicology in vitro : an international journal published in association with BIBRA

Volume

95

DOI

10.1016/j.tiv.2023.105755

Keywords

Attachment and metabolic activity; Cardiomyocyte; Macrovipera lebetina obtusa venom; Metalloproteinases; Phospholipase A(2)

Abstract

The Caucasian viper Macrovipera lebetina obtusa (MLO) is one of the most prevalent and venomous snakes in the Caucasus and the surrounding regions, yet the effects of MLO venom on cardiac function remain largely unknown. We examined the influence of MLO venom (crude and with inhibited metalloproteinases and phospholipase A) on attachment and metabolic activity of rat neonatal cardiomyocytes (CM) and nonmyocytes (nCM), assessed at 1 and 24 h. After exposing both CM and nCM to varying concentrations of MLO venom, we observed immediate cytotoxic effects at a concentration of 100 μg/ml, causing detachment from the culture substrate. At lower MLO venom concentrations both cell types detached in a dose-dependent manner. Inhibition of MLO venom metalloproteinases significantly improved CM and nCM attachment after 1-hour exposure. At 24-hour exposure to metalloproteinases inhibited venom statistically significant enhancement was observed only in nCM attachment. However, metabolic activity of CM and nCM did not decrease upon exposure to the lower dose of the venom. Moreover, we demonstrated that metalloproteinases and phospholipases A are not the components of the MLO venom that change metabolic activity of both CM and nCM. These results provide a valuable platform to study the impact of MLO venom on prey cardiac function. They also call for further exploration of individual venom components for pharmaceutical purposes.

Department

Pharmacology and Physiology

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