Purinergic system as a potential target for inflammation and toxicity induced by thymol in immune cells and tissues

Thymol is a phytochemical component present in many plants used as food additive in order to promote animal growth due to its several biological properties. However, possible side effects of thymol remain poorly known limited to few reports. In this sense, we evaluated the enzymes of the purinergic signaling such as, ectonucleoside triphosphate diphosphohydrolase (NTPDase), 5'-nucleotidase and adenosine deaminase (ADA), that play an important role on toxicity induced by excessive adenosine triphosphate (ATP) content in the extracellular environment. Thus, the aim of this study was to evaluate whether purinergic signaling could be considered a potential target of thymol-induced inflammation, and the toxicity in tissues and immune cells of mice after thymol administration. NTPDase activity (ATP as substrate) in serum, spleen, and splenic lymphocytes was lower after 30 days of oral treatment at doses of 10, 20, and 40 mg/kg of thymol, while ADA activity was stimulated at 20 and 40 mg/kg. No differences were observed between groups regarding NTPDase (ADP as substrate) and 5'-nucleotidase activities in all evaluated tissues. Based on these evidences, adenine nucleotide hydrolysis is modified in serum, spleen, and splenic lymphocytes of mice treated with thymol, contributing to inflammation and toxicity by a reduction on ATP hydrolyses and its possible accumulation in the extracellular medium and increased Ado desamination and its possible reduction in the extracellular environment, leading to a self-sustained pro-inflammatory deleterious cycle. In summary, all tested thymol concentrations induced inflammation and toxicity in tissues and immune cells of treated mice.