Characteristics of biomarkers of the toxicity of okadaic acid in vivo

Okadaic acid (OA) is relating to the number of seafood toxins causing diarrhea. At the present time, there was determined the toxicity index of OA; the main target molecules of its action, its role as a promoter of tumor processes and apoptosis have been investigated. However, in the available literature, data on the toxicokinetics of OA and molecular biomarkers of its action for warm-blooded animals are practically absent. The purpose of this work was to determine biomarkers of toxicity of OA in experiments in vivo and ex vivo. The experiment was performed on 74 male Wistar rats with an initial body weight of 100 ± 10 g. In the work, there was used a solution of OA in methanol, produced by “Fermentec Ltd.” (Israel). Prior to the studies, methanol was removed from the preparation. To obtain working dilutions of the toxin, aliquots of the alcoholic OA solution with a concentration of 10 ppm were diluted with a sterile solution of 0.15M NaCl to obtain solutions with a concentration of OA of 50, 100 and 150 ppb. These solutions were administered to the rats in doses of 1 ml/kg of body weight intraperitoneally. The animals of the control groups were injected with NaCl solution. Excretion of animals from the experiment was carried out 6, 24 and 168 hours after the administration of OA preparations by decapitation under ether anesthesia. The mass of internal organs, biochemical and hematological blood indices, the activity of glutathione peroxidase, non-protein thiols in the liver, cytokine levels of IFN-ɤ, IL-10, IL-17A in blood plasma and liver cell lysates, liver cell apoptosis, malonic dialdehyde level in the liver were analyzed. Studies have shown minimal manifestations of toxic effects of OA in case of intraperitoneal administration (shifts in the ratio of neutrophils and lymphocytes, increased activity of AST, changes in the activity of glutathione peroxidase) to be observed even at a dose of 50 μg/kg of body weight. Taking into account the safety factor of 3, the ARfD level of OA should be revised and accepted to be equal to 0.27 μg/kg of body weight. The data obtained indicate the need for additional risk assessments of this toxin for the health of consumers and, possibly, a revision of the established values of the safe content of this toxin in mollusks. For the first time, there was shown the possibility of using the following marker of toxic action of OA: non-protein thiols, the activity of glutathione peroxidase, and the content of malonic dialdehyde in the liver.