Investigation of the development of tolerance to diazinon in rats. [M.Sc. thesis] | Ispitivanje razvoja tolerancije na diazinon kod pacova. Magistarska teza

Investigation in vitro had as an aim to define: influence of treatment with 1/10 of diazinon peroral LD50 on contractions of isolated rat diaphragm, caused by electric field stimulation (EFS), after 14 and 28 days af treatment; influence of treatment with 1/10 of peroral LD50 of diazinon on contraction of the isolated ileum caused by electric field simulation, as well as influence on amplitude of spontaneous contractions; influence of treatment with 1/10 peroral LD50 of diazinon, on the effect of increasing concentrations of acetylcholine on isolated rat ileum, after 14 or 28 days of treatment. Results of this research show that low peroral dose of diazinon that is applied to rats repeatedly, during longer period of time, leads to poisoning which manifests itself in clinical symptoms only few days after. Clinical symptoms of poisoning, decrease of body weight and lethality are present in the period of 6th till 14th day of diazinon treatment, and afterwards they disappear, although cumulatively taken dose of diazinon is increased. This surley points to development of tolerance and activity of certain systems of adaptation on constant presence of organophosphate in organism. Gathered clinical result are compatibile with significant decreasing of AChE activity in erythrocytes of treated animals, nevertheless, activity of this enzyme is still not normalized in period of disappearing clinical symptoms of poisoning. On the other hand AChE in diaphragms, shows decreasing of activity in period from 7th till 14th day of treatment with diazinon, and then intensively recovered, especially parallel with disappearing of clinical symptoms of poisoning, normalizing body weight and stopping mortality. Apart from this, is obvious that adaptation is taking place with mechanism of down regulation nicotine and muscarine receptors, with that we can explain both increase and after normalization of contractions of isolated diaphragms and ileum of treated rats. Based on this results conclusion is that the tolerance phenomena on poisoning of organophosphate after longer intake of smaller doses, is developed due to bigger number of different adaptation mechanisms. This refers above all, to different cholinesterase activity, as well as adaptive regulatory mechanisms of nicotine and muscarine receptors.