Related Experiment Videos
Pathogenesis of myonecrosis induced by crude venom and a myotoxin of Bothrops asper
Abstract:
The pathogenesis of skeletal muscle necrosis induced by crude Bothrops asper venom and isolated myotoxic phospholipase was studied using light and electron microscopy. White mice were injected intramuscularly with a dose of 2.5 micrograms/g and tissue samples were taken at 30 min and 1, 3, 6, 12, 24, and 48 hr. Toxin-injected muscle showed localized wedge-shaped lesions ("delta lesions") by 30 min, which included disrupted plasma membranes. At 1 and 3 hr the predominant type of necrotic cell contained clumped myofibrils in which individual myofilaments were indistinguishable. At later time periods there was a relaxation and redistribution of myofilaments resulting in a more homogeneous and hyaline appearance of necrotic cells. Some mitochondria were swollen and had flocculent densities, and most of them were disrupted, having only one membrane and vesiculated cristae. The basal lamina was intact at all time intervals. Phagocytosis of muscle cell debris started at 3 hr and was prominent by 24-48 hr. In crude venom-injected muscle many cells showed pathologic features identical to those observed after myotoxin injection. Crude venom also induced hemorrhage which was evident 30 min after injection, reaching its highest level by 12 hr. At 3, 6, and 12 hr some cells were undergoing different pathologic changes which appeared to be due to ischemia. Although these cells were irreversibly damaged, as indicated by ruptured plasma membrane, their myofibrillar structure was better preserved than that of toxin-affected cells. The Z line was absent, but A, I, H, and M bands were intact. As a result of Z line loss, sarcomeres were disoriented. It is proposed that the myotoxin induces myonecrosis by first altering the integrity of the plasma membrane, thereby increasing the permeability to calcium, other ions, and molecules which leads to death of the cell. Crude venom affects muscle cells in two ways: by direct action of myotoxin (s) and by ischemia due to hemorrhage.
Insights
Bothrops asper venom causes skeletal muscle necrosis through myotoxin-induced plasma membrane damage and ischemia from hemorrhage. This study details the cellular pathology and progression of muscle damage in mice.
Area of Science:
- Toxicology
- Pathology
- Cell Biology
Background:
- Skeletal muscle necrosis is a severe condition.
- Bothrops asper venom is known for its myotoxic effects.
- Understanding venom-induced muscle damage is crucial for treatment.
Purpose of the Study:
- To investigate the pathogenesis of skeletal muscle necrosis induced by crude Bothrops asper venom and its isolated myotoxic phospholipase.
- To elucidate the cellular and subcellular changes occurring in muscle tissue following envenomation.
Main Methods:
- Light and electron microscopy were employed to examine muscle tissue.
- White mice were injected intramuscularly with venom or myotoxin.
- Tissue samples were collected at various time points (30 min to 48 hr) post-injection.
Main Results:
- Myotoxin induced rapid plasma membrane disruption and myofibrillar clumping, leading to myonecrosis.
- Crude venom caused similar myotoxic effects plus hemorrhage and ischemia.
- Cellular damage progressed from membrane disruption to myofibrillar disorganization and eventual phagocytosis.
Conclusions:
- Myotoxin initiates myonecrosis by compromising plasma membrane integrity, increasing calcium influx.
- Crude Bothrops asper venom exerts dual effects: direct myotoxicity and indirect damage via ischemia due to hemorrhage.
- The study provides detailed insights into the sequential pathological events in venom-induced myonecrosis.