Memantine hydrochloride versus pralidoxime in the treatment of chlorpyrifos - induced pulmonary toxicity in albino rats

ABSTRACT

Chlorpyrifos [CP] is a broad-spectrum organophosphorus insecticide that is widely employed for control of many agricultural and household pests. It is extremely toxic to humans and animals. The antidotal therapy of acute organophosphorus poisoning hasn't been satisfactorily solved till now in spite of the knowledge of the basic mechanism of action of these toxic substances. The aim of this work was to investigate the effect of acute CP intoxication on the alveolar structure of albino rats and to compare the therapeutic efficacy of memantine hydrochloride [MEM]k, and amantadine derivative, and the currently used oxime [pralidoxime chloride [2-PAM] Six groups of rats were used in this study, each of ten animals. The control groups [group I, II, III], The intoxicated group [group IV that received CP in a dose of 40 mg/kg body weight orally for two consecutive days and the treated groups which, included group V [rats treated with PAM and atropine sulfate [ATS] for 2 days]. Blood samples were collected from all animals one hour after drug administration for estimation of plasma acetylcholinesterase [AchE] enzyme level. The animals were sacrificed 24 hours after the last injection and the lungs of each animal were examined histologically by the light and the transmission electron microscopes. The present study demonstrated significant reduction in the level of plasma AchE in CP group. On he other hand, the enzyme levels increased in both groups of CP and MEM and CP and 2-PAM [but still less than normal control levels]. The enzyme reactivation was much more evident with MEM treatment. Histologically, CP treatment resulted in severe pulmonary congestion with extravasation of blood cells, thickening of pulmonary interstitial and evident ultratructural aerations of the alveolar structures. Treatment with MEM after CP resulted in greater alternations of CP-induced alveolar lesions than 2-PAM treatment. In conclusion, he results of this study suggested that CP is a potent pulmonary toxicant, and MEM is more effective reactivator of CP-inhibited AchE than 2-PAM. It also offered greater alveolar protection than 2 PAM