cobra-cardiotoxin-proteins and Body-Weight

Myostatin (MSTN) is a muscle-specific secreted peptide that functions to limit muscle growth through an autocrine regulatory feedback loop. Loss of MSTN activity in cattle, mice, and humans leads to a profound phenotype of muscle overgrowth, associated with more and larger fibers and enhanced regenerative capacity. Deletion of MSTN in the mdx mouse model of Duchenne muscular dystrophy enhances muscle mass and reduces disease severity. In contrast, loss of MSTN activity in the dyW/dyW mouse model of laminin-deficient congenital muscular dystrophy, a much more severe and lethal disease model, does not improve all aspects of muscle pathology. Here we examined disease severity associated with myostatin (mstn-/-) deletion in mice nullizygous for delta-sarcoglycan (scgd-/-), a model of limb-girdle muscular dystrophy. Early loss of MSTN activity achieved either by monoclonal antibody administration or by gene deletion each improved muscle mass, regeneration, and reduced fibrosis in scgd-/- mice. However, antibody-mediated inhibition of MSTN in late-stage dystrophic scgd-/- mice did not improve disease. These findings suggest that MSTN inhibition may benefit muscular dystrophy when instituted early or if disease is relatively mild but that MSTN inhibition in severely affected or late-stage disease may be ineffective.

Topics: Aging; Animals; Body Weight; Cobra Cardiotoxin Proteins; Disease Models, Animal; Fibrosis; Gene Deletion; Genotype; Hydroxyproline; Mice; Mice, Transgenic; Muscular Dystrophies, Limb-Girdle; Myostatin; Time Factors; Transforming Growth Factor beta

To evaluate the toxicity of VRCTC-310-Onco (Crotalus durissus terrificus crotoxin + cardiotoxin from Naja naja atra), 10 Sprague-Dawley rats were implanted with intraperitoneal slow-release devices and subjected to treatment with 0.5 microgram/g body weight/d for 14 days. Biochemical evidence at days 7 and 14 showed blood, muscular, renal and metabolic disturbance, mostly reversed by day 28. No significant changes were found in necropsy. The limited toxicity of i.p. VRCTC-310-Onco in rats deserves further study.

Topics: Animals; Antineoplastic Agents; Body Weight; Cholesterol; Cobra Cardiotoxin Proteins; Crotoxin; Drug Combinations; Eating; Erythrocytes; Infusion Pumps, Implantable; Injections, Intraperitoneal; Leukocytes; Liver; Male; Rats; Rats, Sprague-Dawley; Triglycerides; Water-Electrolyte Balance