Acute toxic effects of Bothrops atrox venom on calcium homeostasis and bone tissue in mice

Abstract

Bothrops atrox is a terrestrial pit viper inhabiting the Amazon region. The venom of B. atrox acts almost immediately at the site of the bite, leading to significant tissue damage, but also affects different organs. The present study investigated the acute impact of intraperitoneally administered B. atrox venom on bone tissue integrity and calcium homeostasis in mice. Plasma, bone homogenate, and urine samples from adult male and female Swiss mice (30 ± 2 g/mouse) were analyzed to assess calcium and phosphorus levels. Additionally, we examined bone oxidative stress parameters alongside histological and scanning electron microscopy (SEM) analysis. Our findings showed that B. atrox envenoming results in profound phosphocalcic homeostasis disturbances with hypercalcemia, hypophosphatemia, and decreased calcium and phosphorus bone content. We also observed increased reactive oxygen species and malondialdehyde, and consumption of antioxidants. Histological examination and SEM of bone tissue revealed thinning and discontinuity of trabecular bone and a significant reduction in intertrabecular links. In conclusion, B. atrox envenoming profoundly impacts bone metabolism and structural integrity in mice. The venom induces substantial alterations in calcium and phosphorus homeostasis, elevates oxidative stress, and disrupts the antioxidant defense system. Histological and SEM analyses reveal extensive damage to the trabecular bone architecture, reinforcing the harmful effects of the venom on skeletal health. These results underscore the need for further research to better understand the acute and long-term implications of B. atrox envenoming, particularly regarding its potential impact on human bone.