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

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

Histological study of the effect of haloperidol on the corpus striatum of Albino rats and the possible neuro-protective role of vitamin E

Halperidol [HP] is a high potency antipsychotic drug used in treatment of schizophrenia. One of its major side effects is Tardive Dyskinesia [TDD] which is a syndrome of irreversible involuntary movements in tongue, face, arms and legs. Different mechanisms were proposed to explain the pathphysiology of TD and to suggest the proper treatment of this iatrogenic effect caused by HP. The most accepted theory could be histological alterations in the striatum caused by an oxidative stress mechanism and hence the trial of vitamin E [being an antioxidant] as a protective agent against HP-induced TD. The study was performed to investigate the effect of HP on the corpus striatum of rat and the possible neuroprotective role of vitamin E. The present study was carried out on forty adult male albino rats which were divided into four groups; the control group, vitamin E group received only vitamin E orally in a dose of 100 mg/kg/day for 4 consecutive weeks, the HP group received HP in a dose of 40 mg/kg/day for 4 consecutive weeks and the HP and vitamin E group received 100 mg/kg vitamin E in conjunction with HP for the same period. Clinical observation for VCMs [analogue of TD] was made during the period of experiment. At the end of four weeks, animals were sacrificed and brain specimens were prepare for histological study of the basal ganglia by light microscopy using H and E. and DOPA reaction. There were different histological alternations in neurons of the striatum in the HP-treated group, which were in the form of distortion, cellular infiltration,, shrinkage and hypereosinophilia of the cytoplasm. Other neurons showed cytoplasmic vacuolations, Co-administrations of vitamin E, reduced the HP-induced striatal neuronal changes, thus, vitamin E could be of value as a neuroprotective agent against HP-induced striatal changes in humans