Elevation of protein in the diet from 19 to 59 per cent ,and kept isocaloric significantly improved the growth over a period of 20 days of male albino rats exposed to the toxic stress of DFP, EPN and Malathion.Marked changes in the metabolism and pharmacotbxicological activity of drugs and xenobiotics have been reported due to alteration of the nutritionalfactorsl. Dietary protein increases2 the concentration of rnicrosomal drug metabolising enzymes mainly localised in the liver ~nicrosomes which readily metabolise and detoxify' any xenobiotic. However, for a chemical that gets bioactivated or biotoxicated the test animal is exposed to the stress of a more toxic metabo!ite for a longer period when on High Protein Diet (HPD).The present study deals with the effect of HPD on the growth rate of albino rats under toxicity of organophosphorus (OP) compounds like diisopropylphosphorofluoridate (DFP), o-ethyl o-(Cnitrophenyl) phenyl phosphonothioate (EPN) and Malathion [o, o-dimethyl S(1, 2 -dicarbethoxy ethyl) phosphorodithioate]. Apart from DFP which undergoes direct detoxication in a living system and is a structural analogue of nerve gas Sarin (Methyl isopropyl phosphonofluoridate), EPN and Malathion undergoes biotoxication.The aim was to find out whether HPD could be used as a prophylactic against nerve gas poisoning which are of organophosphorus origin4. Male albino rats of wistar strain (body wt. 130 f 15 g) were divided into eight groups of eight animals each. Groups A and B were controls being given Standard Diet (SD) containing 19 per -----
Rats were pretreated with phenobarbitol [PB (75 mg/kg, IP)] for 3 days and subsequently injected with parathion, an organophosphorous insecticide, which requires microsomal activation for its anticholinesterase effect or with dichlorovos, a cholinesterase (ChE) inhibitor as such. The difference in the mortality and spontaneous regeneration of inhibited plasma ChE by IP administration of the two insecticides was compared. A single dose of 10 mg/kg parathion caused 100% mortality in PB-untreated rats, but effected no mortality in PB-pretreated rats. A lower dose (7.5 mg/kg) of parathion resulted in plasma ChE levels which were 5, 5, 17, and 93% of initial values in PB-untreated rats and 85, 97, and 92% of initial values in PB-pretreated rats at 2-hr, 1-3-, and 5-day periods, respectively. Mortality resulting from single dose of 30 mg/kg dichlorovos was 30% in PB-pretreated, as well as untreated rats. A lower dose of dichlorovs (20 mg/kg) resulted in plasma ChE activity which was 48, 82, 90, and 97% of initial levels in PB-untreated rats, and 60, 100, 100, and 130% in PB-pretreated rats at 2 hr, 1, 3, and 5 day's, respectively. Administration of 2 mg/kg parathion for 3 days did not affect cytochrome P-450 levels in liver microsomes, but administration of 6 mg/kg dichlorovos for 3 days caused greatly lowered levels of liver microsomal cytochrome P-450, resulting from its inactivation to cytochrome P-420. Phenobarbital caused accelerated in vitro ChE regeneration in the case of dichlorovos-inhibited enzyme in the plasma, but not in the case of parathion-inhibited enzyme.
An acute dose ofDFP equivalent to 50 per cent of the LDsocauses glycogenolysis and hyperglycemia in male albino rats. The hyperglycemic effect can atleast be partially suppressed by the administration of insulin. Under sub-acute dose equivalent to 5 per cent of the LD SO' there is glycogenolysis but no change in blood glucose . The action of DFP on carbohydrate metabolism seems to be mediated through adrenal gland. DFP also increases the glycolytic rate, suppresses the LDH activity and is hepatotoxic.Diisopropyl phosphorofluoridate (DFP) is a highly toxic organophosphorus compound (OPC) categorised under acetylcholinesterase inhibitors. Amongst earlier literature on the effect of OPCs on carbohydrate metabolism, Matin and Siddiquil found increase in blood glucose and reduction in glycogen in various brain structures in rats after treatment with malathion. Samson, et al2 observed that Soman has greater impact on brain regional glucose use than DFP .Present inv~stigation is aimed at obtaining more insight into the effect of DFP on certain aspects of carbohydrate metabolism. The first aspect comprised of study of the effect of acute and sub-acute doses of DFP on liver glycogen and blood glucose levels in male albino rats and the effect of simultaneous administration of insulin. The second aspect consisted of study of the effect of an acute dose of DFP on liver glycogen, total free (unconjugated) catecholamine levels in blood and lactate For the first phase of study (Table 1), male albino rats (body weights 150:t10 g) wcre divided into four groups of eight animals each. The group 1 served as control. The animals of this group were injected sc with equivalent diluents of DFP .The group 2 animals were similarly injected with an acute dose (50 per cent of the LD50) of DFP . The animals of group 3 received the same dose of DFP as group 2, together with 1.0 unit/kg of insulin. The group 4 animals received, daily sub-acute doses (5 per cent of the LD50) of DFP for a 22 day period. The dilutions of DFP were made in distilled water from a 10 per cent stock solution of the pure compound in propylene glycol. The LD50 of DFP was predetermined3 in this laboratory and found to be 3.3 mg/kg by sc route. A portion of liver tissue (approx 2 g) was collected from each animal in tubes containing 30 per cent KOH (6 ml) for glycogen estimations and specimens of blood (approx 4 ml)for blood glucose estimations in tubes containing a small quantity (20 mg) of NaP as anticoagulent, either after 75 min or 24 hr from the last dose DFP depending whether the studies were made under acute or sub-acute toxicity conditions. Glycogen was isolated from liver as described by Hawk4~ hydrolysed and estimated as glucose by Dubois methods. Blood glucose was estimated by glucose oxidase method6. Table 1 Effect of an acute dose of DFP on liver glycogen and blood glucose followed by administration of insulin + effect of daily, sub-acute doses of DFP for a 22. day period on liver glycogen and blood glucose* 6.34 :t 0. For the second phase (Table 2),...
ABSTRACT-The present investigation deals with determining the efficacy of a high protein diet (HPD) in combating toxicity in albino rats of some organophosphorus compounds (OPCs) that follow dissimilar metabolic patterns in a living system. As assessed by an increase or decrease in the levels of some biochemical and nutritional parameters, the high protein diet containing 59% protein seems to have a beneficial effect in alleviating toxicity of low but prolonged doses of OPCs over the standard diet (SD) containing 19% protein. OPCs undergoing direct detoxication in a living system like diisopropyl phosphoro-fluoridate (DFP) appear to be more susceptible to HPD than those undergoing biotoxication like EPN (0-ethyl 0-p-nitrophenyl phenyl phosphonothioate) and malathion (S-(1,2-dicarbethoxyethyl) 0,0-dimethyldithio phosphate).
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