Salicylate and cocaine: interactive toxicity during chicken mid-embryogenesis

Increased free radical production, due to ischemia and reperfusion, has been postulated as a cause of cocaine’s (COC) developmental toxicity. Salicylate reacts with hydroxyl free radicals (√OH) to form stable, quantifiable reaction products, which can be measured with high-pressure liquid chromatography (HPLC). To determine if chicken embryos’ brains and hearts were exposed to increased √OH concentrations after injection of COC, an injection of a nontoxic dose of sodium salicylate (NaSAL, 100 mg/kg egg, or 5 mg/egg), followed by 5 injections of COC (13.5 mg/kg or 0.675 mg/egg, every 1.5 h), was administered to eggs containing embryos on the 12th day of embryogenesis (E12). In addition to finding increased √OH concentrations in E12 embryonic hearts and brains, we observed that the developmental toxicity of COC, manifest as vascular disruption (hemorrhage) and lethality, was enhanced by NaSAL injection. These results confirm and extend results of similar experiments performed upon older embryos (E18), and indicate that increased √OH concentration in embryonic tissues after COC exposure and toxic interactions of COC and NaSAL can also occur at an earlier stage of development. The results are discussed in light of possible exposure of human fetuses to both COC and salicylates, since COC-abusing pregnant women can be misdiagnosed with pre-eclampsia and aspirin is used to treat this syndrome.