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

Toxicol In Vitro. 2024 Mar:95:105755. doi: 10.1016/j.tiv.2023.105755. Epub 2023 Dec 6.

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 A2) 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 A2 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.

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

MeSH terms

  • Animals
  • Metalloproteases
  • Myocytes, Cardiac
  • Phospholipases A2 / metabolism
  • Rats
  • Viper Venoms / toxicity
  • Viperidae* / metabolism

Substances

  • Viper Venoms
  • Phospholipases A2
  • Metalloproteases