Dichlorvos (DDVP) and monocrotophos (MC) are systemic insecticides and known to produce cholinergic and non-cholinergic effects. Individual toxic effects of these chemicals are known but their combined effects have not been studied. We studied the effect of concomitant exposure to DDVP and MC on selected biochemical variables suggestive of liver damage, changes in whole brain biogenic amines levels, acetylcholinesterase (AchE) and monoamine oxidase (MAO) activities in rats. Female rats were exposed to DDVP (2.5 mg/kg subcutaneously) and MC (1.8 mg/kg oral) either individually or in combination for 4 weeks. We observed significant decrease in more pronounced depletion in norepinephrine (NE) and dopamine (DA) levels during co-exposure to DDVP and MC. Brain AChE activity increased and activity of MAO showed significant depletion on co-exposure to DDVP and MC. Brain glutathione (GSH) and oxidized glutathione (GSSG) ratio decreased significantly during exposure to DDVP or MC while co-exposure to these toxicants led to a more pronounced depletion of GSH: GSSG ratio. Serum aspartate amino transferase (AST) and alkaline phosphatase (ALP) activities increased significantly on exposure to MC suggesting liver injury, while DDVP alone had no effect on these variables. There were no effects of DDVP and MC exposure on haematological biochemical variables except for depletion in serum glucose level after MC exposure which was more pronounced DDVP + MC during co-exposure. It can be concluded that only moderate synergistic effects occur between MC and DDVP during co-exposure. A more detailed study with variable doses, prolonged exposure and alterations in different brain regions is recommended.

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Objectives:To find out the analgesic and anti-inflammatory activity, if any, of Amifostine [S-2(3 amino propyl amino) ethyl phosphorothioate], DRDE-07 [S-2(3 amino ethyl amino) ethyl phenyl sulphide] and their analogs DRDE-30 and DRDE-35, the probable prophylactic agent for sulphur mustard (SM).Materials and Methods:In order to find out the analgesic activities of the compounds two methods were employed, namely, acetic acid-induced writhing test and formalin-induced paw licking. The persistent pain model of formalin-induced hind paw licking was carried out to test the effect of the compounds on neurogenic pain or early phase (0 to 5 minutes) and on the peripheral pain or the late phase (15 to 30 minutes). To test the effect of the compound in acute inflammation, carrageenan-induced hind paw edema was carried out. This model of inflammation involves a variety of mediators of inflammation.Results:DRDE-07 (81.7%) and DRDE-30 (79.4%) showed significant reduction in the acetic acid-induced writhing test. DRDE-07 (93.1%), DRDE-30 (82%), and DRDE-35 (61.3%) showed significant reduction in the second or late phase of formalin-induced paw licking. All the analogs (more than 60%) including amifostine (43.9%) showed significant reduction of paw edema in the carrageenan-induced paw edema in mice.Conclusion:The analgesic and anti-inflammatory activity of the antidotes were comparable with aspirin.

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