The antagonistic effect of tetracycline on the biological activity of cholera toxin

Tetracycline was evaluated for its ability to neutralize the toxic effects of cholera toxin in mice. The toxicity of cholera toxin was evaluated by measuring the weights and the leukocyte numbers of the spleen and thymus of mice. Forty-eight hours after intraperitoneal injection of 16 μg of cholera toxin, the mice showed significant reductions in both the spleen and thymus weights (64.3 % and 63.9 %) and in the spleen and thymus leukocyte numbers (67.7 % and 89.7 %). In vitro preincubation of cholera toxin with a 2-fold excess of tetracycline (wt/wt) significantly decreased the cholera toxin-induced toxicity to the spleen and thymus in mice. However, in vivo pretreatment of mice with tetracycline only protected against cholera toxin- induced spleen toxicity, but not against cholera toxin-induced thymus toxicity. The detoxifying activity of tetracycline was also evaluated by ileal loop secretory activity and vascular permeability factor assays in rabbits. Coincubation of cholera toxin with an equal or 4-fold greater amount of tetracycline significantly decreased the ileal loop secretory and vascular permeability factor activities of cholera toxin by 51.9 % and 51.2 %, respectively. The lethality of cholera toxin in mice was completely blocked by a two-fold excess of tetracycline (wt/wt) treatment to toxin.