Salicylate and cocaine: Interactive toxicity during chicken mid-embryogenesis

Increased free radical production, due to ischemia and reperfusion, has bee n postulated as a cause of cocaine's (COC) developmental toxicity. Salicyla te reacts with hydroxyl free radicals ((OH)-O-.) to form stable, quantifiab le reaction products, which can be measured with high-pressure liquid chrom atography (HPLC). To determine if chicken embryos' brains and hearts were e xposed to increased (OH)-O-. concentrations after injection of COG, an inje ction of a nontoxic dose of sodium salicylate (NaSAL, 100 mg/kg egg, or 5 m g/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 embr yogenesis (E12). In addition to finding increased (OH)-O-. concentrations i n E12 embryonic hearts and brains, we observed that the developmental toxic ity of COG, manifest as vascular disruption (hemorrhage) and lethality, was enhanced by NaSAL injection. These results confirm and extend results of s imilar experiments performed upon older embryos (E18), and indicate that in creased (OH)-O-. concentration in embryonic tissues after COC exposure and toxic interactions of GOC and NaSAL can also occur at an earlier stage of d evelopment. The results are discussed in light of possible exposure of huma n fetuses to both COC and salicylates, since COG-abusing pregnant women can be misdiagnosed with preeclampsia and aspirin is used to treat this syndro me. (C) 2001 Elsevier Science Inc.