Growing male rats that weighed 120 +/- 5 g were kept for 30 days on the following synthetic diets: high protein diet (HPD), 59% casein; high fat diet (HFD), 50% saturated fat; and normal diet (ND), 19% casein, 10% saturated fat, and 60% sucrose. Other essential dietary ingredients were included in all the diets. All animals were injected at the end of the 30-day period with parathion [10 mg/kg intraperitoneal (ip) injection as a single dose] or dichlorvos (30 mg/kg ip as a single dose) to compare the effect of dietary pretreatments on mortality from parathion and dichlorvos. A lower dose of parathion (7.5 mg/kg) and dichlorvos (20 mg/kg) was employed in another set of experiments to compare the spontaneous regeneration of plasma and red blood cell (RBC) cholinesterase (ChE) activity at 2 hr, 1 day, 3 days, and 5 days after administration of parathion or dichlorvos. The effect of these diets on hepatic microsomal oxidases was also determined. Results showed that diets per se did not affect initial plasma and RBC ChE activity. The HPD and HFD significantly protected against mortality from parathion but not from dichlorvos. Hepatic microsomal cytochrome P-450 and aminopyrine demethylase activity were unchanged, but aniline hydroxylase activity was increased significantly by HPD and HFD. Parathion oxidase in hepatic microsomes was significantly increased in rats fed HFD only. For the HPD, spontaneous regeneration of ChE diminished in RBCs in parathion-intoxicated rats and in plasma and RBCs of dichlorvos-intoxicated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Rats were injected intraperitoneally with phenobarbital (PB) and 3-methylcholanthrene (MC), 80 and 20 mg/kg, respectively, for 3 consecutive days and then administered threshold lethal dose of the organophosphorus insecticide, parathion, 10 mg/kg i.p. to compare its toxicity in these, with those fed high fat, diet (HFD-50% saturated fat, and normal diet (ND-10% saturated fat) for 30 days. Hepatic microsomes of these four groups of rats without the parathion administration were also analysed to evaluate toxicity and metabolism of the insecticide in relation to some physico-chemical changes in microsomal membranes. Results showed that in comparison to ND, all three pretreatments (PB, MC and HFD) significantly decreased parathion toxicity, increased microsomal oxidase activity and elevated microsomal cholesterol/phospholipid ratio. However, microsomal cytochrome P-450 was significantly raised only in PB and MC, and microsomal fluidity was significantly raised only in MC, as measured by DPH-fluorescence polarization technique.
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.
Rats were injected intraperitoneally with phenobarbital (PB) and 3-methylchol-anthrene (MC) which are microsomal enzyme inducers, and methyl iodide (Mel), cobalt chloride (COCI2) and tri-o-cresyl phosphate (TOCP) which are inhibitors of the enzymes glutathione transferase, cytochrome (cyt) P-450 and carboxylesterase, respectively, and then challenged with soman (i.p.) to know its LD50. Pretreatment with PB and MC increased and TOCP decreased, whereas Mel as well as COCI2 did not alter the LD50 value of soman in rats. The ½LD50 dose of soman did not affect the liver microsomal cyt P-450 level, but significantly lowered carboxylesterase (CaE) and cholinesterase (ChE) activities in liver microsomes and in blood plasma. Induction of plasma CaE was more important than microsomal CaE in PB-mediated protection against soman toxicity. Gel filtration of plasma into four protein fractions for their relative soman binding capacity showed that a high-molecular-weight protein fraction (180,000 daltons on SDS-PAGE) which had no CaE activity could bind soman 6 times more than the low-molecular-weight CaE-containing protein fraction (60,000 daltons on SDS-PAGE).
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