Effect and mechanism of action of methomyl and cypermethrin insecticides on kynurenine metabolizing enzymes of mouse liver

Abstract

The effect of methomyl and cypermethrin insecticides on the B₆‐dependent kynurenine hydrolase(KH) and kynurenine aminotransferase (KATE) was studied. These insecticides induced pronounced inhibition on the (KH) and (KATE) enzymes after single dose treatment. Repeated doses of methomyl induced inhibition on the (KH) and (KATE) activities, whereas repeated treatment with cypermethrin had no effect on the activities of these enzymes. In vitro methomyl inhibited (KH) and (KATE) enzymes at 10 M up to 10^‐3 M, through a competitive mechanism. Methomyl and cypermethrin are capable of causing alterations in the kynurenine metabolizing enzymes of mouse liver.     

Effects of deltamethrin on hepatic microsomal cytochrome p450‐dependent monooxygenases in carp

Abstract The in vivo effects of sublethal concentrations of deltamethrin (DM), a pyrethroid insecticide, on the hepatic microsomal cytochrome P450 (Cyt P450) content and the Cyt P450‐dependent monooxygenase activities (para‐nitrophenetole‐O‐deethylase, pNPOD; aminopyrene‐N‐demethylase, APND; ethylmorphine‐N‐demethylase, EMND; 7‐ethoxycoumarin‐O‐deethylase, ECOD; and ethoxyresorufin‐O‐deethylase, EROD) were examined in adult carp (Cyprinus carpió L.).

0.2 μg/1 DM treatment resulted in significant increases in APND, EMND and ECOD activities, whereas 2 μg/1 DM resulted in significant inhibitions of all studied isoenzyme activities with the exceptions of pNPOD and APND after 72 h. EROD was the only enzyme for which a slight increase in activity was observed. On repeated treatment, Cyt P450 could not be detected after 48 h, but the Cyt P420 level increased. All tested isoenzyme activities were inhibited, with the exception ofthat of EROD, which was enhanced.

All these changes in enzyme activities and Cyt P450 content demonstrate the effects of DM on fish. DM treatment at low concentration is presumed to cause induction of the Cyt P450‐dependent monooxygenases which may lead to faster metabolization of the insecticide. In contrast, DM at higher concentration strongly inhibited the activities of the studied enzymes. This finding may be due to the damaging effect of DM on the xenobiotic metabolizing enzyme systems offish.     

Toxicity and biochemical impact of certain oxime carbamate pesticides against terrestrial snail,Theba pisana (Müller)

Abstract

The bran toxic baits (0.5 % w/w) of five oxime carbamate pesticides; aldicarb, aldoxycarb, methomyl, oxamyl and thiofanox were tested for their molluscicidal activity against Theba pisana snails under Laboratory conditions. In addition, the in vivo effects of these compounds on seven vital enzymes namely Acetylcholin‐esterase (AchE), glutathion‐S‐transferase (GST), glutamic oxlaoacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), acid phosphatase (AcP), alkaline phosphatase (AIP), and adenosine triphosphatase (ATPase) activities of the snail tissue were also investigated after 1,3, and 5 days of exposure. The results showed that methomyl was the most potent candidate, whereas thiofanox was the least effective one against the snails. LT₅₀’s values of aldicarb, aldoxycarb, methomyl, oxamyl and thiofanox were 5.77, 4.69, 2.31, 3.97 and 6.67 days, respectively. Results of the potency of the tested pesticides against AchE activity were in harmony with the toxicity of these compounds to snails. AchE, AcP, and AIP activities were inhibited by the tested pesticides. GST activity was inhibited by aldicarb but stimulated by oxamyl and thiofanox. Methomyl and oxamyl lead to significant elevation of GOT and GPT, whereas thiofanox treated snail induced a reduction of both enzymes activities. Aldicarb and aldoxycarb caused significant induction of ATPase activity.     

Induction of rat hepatic microsomal enzymes by toxaphene pretreatment

Abstract

The effects of pretreatment of rats with toxaphene on hepatic drug metabolizing enzymes and several other parameters of the mixed function oxidase system were investigated. Adult male Sprague‐Dawley rats were fed diets containing 0, 50, 100, 150 and 200 ppm of toxaphene for 14 days. The body weight gain was unaltered as well as the food consumption in all the toxaphene fed groups. There was no change in the weights of brain, kidney, heart, and testes but the liver weight was significantly increased. The thymus weight in all the toxaphene fed groups was decreased. Hydroxylation of pentobarbital and aniline was significantly enhanced in rats exposed to toxaphene. Ethylmorphine‐N‐demethy‐lase activity in the toxaphene treated rats was also elevated. Enhanced hydroxylation of pentobarbital was also evident from the decreased sleeping time following pentobarbital administration. Exposure to toxaphene increased cytochrome P‐450, NADPH‐cytochrome c‐reductase and dehydrogenase in hepatic microsomal fractions. The binding of aniline and hexobarbital to microsomes was also enhanced, suggesting that the intermediate steps in the electron‐transfer system were increased. In conclusion, pretreatment of rats with toxaphene for fourteen days resulted in the induction of the hepatic mixed function oxidase system.     

Liver glutathione content and glutathione‐dependent enzymes of two species of freshwater fish as bioindicators of chemical pollution

Abstract

Glutathione content and glutahione‐dependent enzymes were measured in the liver of two fish species, gudgeon (Gobio gobio) and roach (Rutilus arcasii), from the river Bernesga (Spain) caught downstream and upstream of the waste site of several chemical industries. Animals from contaminated sites display a reduced glutathione concentration and a tendency to the decrease of glutathione S‐transferase activity. Glutathione peroxidase activity was significantly elevated only in the liver of Gobio gobio and glutathione reductase activity in that of Rutilus arcasii. Our data indicate that the glutathione system constitutes a sensitive biochemical indicator of chemical pollution. Relative changes of glutathione and glutathione‐dependent enzymes in both fish species suggest a different susceptibility to toxins.     

Safening activity of natural hydroxamic acids and analogous compounds against herbicide injury to maize

Abstract

Safening activities of natural compounds DIMBOA, DIBOA, and MBOA, as well as synthetic 1,4‐benzoxazin‐3‐ones were tested against acetochlor and EPTC injuries to maize. No safening activities of natural products and from low to moderate activity of synthetic benzoxazinones were observed. In order to explain inefficacy of natural compounds we studied the influence of these molecules on enzymes participating in metabolic detoxication of acetochlor and EPTC. Pretreatment with DIMBOA elevated maize cytochrome P450 levels. Pretreatments with chemicals containing 1,4‐benzoxazin‐3‐one backbone did not alter glutathione S‐transferase enzyme activities. However, all natural products inhibited glutathione S‐transferase activity of roots and shoots in vitro after addition to the enzyme. Safening ineffectiveness of natural hydroxamic acids may be explained by their inhibitory effects on GST enzymes due to their reaction with sulfhydryl groups on the enzyme.     

Induction of glutathione reductase enzyme activity by β‐aminobutyric acid in plant leaves

Abstract

Treatment of pea and tobacco leaf discs with the resistance inducer DL‐β‐amino‐n‐butyric acid (BABA) led to a substantial induction of glutathione reductase (GR, E.C. 1.6.4.2.) enzyme activity. After exposure to 1 mM BABA for 96 hrs, the GR activities were 3.2‐fold and 2.9‐fold higher in pea and tobacco leaf discs, respectively, than GR activities in untreated controls. Elevated GR levels may contribute to the antioxidative protection of plants during pathogen attack.     

Changes in the activities of some digestive enzymes of Channa punctatus,exposed chronically to mercuric chloride

Abstract

The effect of a chronic exposure to sublethal concentration of mercuric chloride (0.3 mg/1) on the activities of some enzymes in the digestive system of the teleost fish Channa punctatus was examined after 15 and 30 days of treatment. Glucose‐6‐phosphatase was significantly inhibited in the intestine and pyloric caeca. No marked alterations were observed in the activities of maltase and lactase except for elevation in maltase activity and inhibition in lactase activity in the intestine and pyloric caeca after 15 days of treatment. Three peptidases (aminotripeptidase, glycylglycine dipeptidase and glycyl‐1‐leucine dipeptidase) showed decreased activities in all parts of the digestive system. A decrease was also observed in the activity of lipase except for the stomach where inhibition after 15 days was insignificant. The results indicate that the activities of all the enzymes examined are inhibited in intestine and pyloric caeca and digestion of proteins and lipids may be more affected by mercury than the digestion of some carbohydrates.     

Genotoxicity of methyl parathion in short‐term bacterial test systems

Abstract

Genotoxicity of the insecticide methyl parathion was investigated in Salmonella typhimurium and Escherichia coli bacterial test systems for the detection of back mutations and DNA‐damage. Methyl parathion was mutagenic to S. typhimurium strain TA100 after activation with rat liver microsomal and cytosolic enzymes. In DNA repair tests, methyl parathion was effective in inducing damage to the S. typhimurium strain TA1538 which lack excision repair compared to the strain TA1978 which is proficient in excision repair mechanisms. Normal laboratory light conditions had no effect on the mutagenicity tests, however, exposure of methyl parathion in the petri dish containing the tester strain TA100 and rat liver microsomal and cytosolic enzymes reduced the mutagenic activity and increased the toxic effects of methyl parathion.     

Herbicide safeners: Tools for improving the efficacy and selectivity of herbicides

Abstract

Safeners (also known as antidotes) are chemical or biological agents that reduce the toxicity of herbicides to crop plants by a physiological or molecular mechanism. Commercialized safeners are mainly chemical compounds that enhance the tolerance of selected grass crops such as maize (Zea mays L.), grain sorghum [Sorghum bicolor (L.) Moench], rice (Oryza sativa L.), and wheat (Triticum aestivum L.) to chloroacetanilide, thiocarbamate, sulfonylurea, imidazolinone, and aryloxyphenoxypropionate herbicides. In practice, safeners are applied either to the crop prior to planting (seed safeners) or to the soil together with the herbicide, formulated as a prepackaged mixture. Safeners act as "bioregulators”; controlling the amount of a given herbicide that reaches its target site in an active form. A safener‐induced enhancement of the metabolic detoxification of herbicides in protected plants is the most apparent mechanism for the action of all commercialized safeners. Herbicide‐detoxifying enzymes such as glutathione transferases (GST), cytochrome P‐450 monooxygenases (CytP450), esterases, and UDP‐glucosyltransferases are induced by herbicide safeners. At the molecular level, safeners appear to act by activating or amplifying genes coding for these enzymes (e.g., GST).     

Evaluation of chlordimeform and degradation products for mutagenic and DNA‐damaging activity in salmonella typhimurium and escherichia coli

Abstract

The mutagenic activity of chlordimeform and two of its breakdown products, 4‐chloro‐o‐toludine and 4‐chloro‐N‐formyl‐o‐toluidine were determined with five histidine dependent strains of Salmonella typhimurium (TA1535, TA1537, TA1538, TA98, TA100) and five tryptophan dependent strains of E. coli WP₂. (WP₂, WP₂uvrA, WP67, CM611, CM571) with and without rat liver microsomal enzymes. 4‐chloro‐o‐toluidine increased the number of the reversions of the S. typhimurium strain TA1535 more than two fold over spontaneous at the concentration of 400 μg/plate.

The results of the DNA repair tests in the Salmonella TA1538/TA1978 and E. coli multirepair deficient systems showed that both breakdown products were active in inducing damage not repaired in at least one repair deficient strain while chlordimeform itself was inactive.     

Effect of some xenobiotics on kynurenine hydrolase and kynurenine aminotransferase of mouse liver

Abstract

The effects of some xenobiotics on the activity of the B₆‐dependent kynurenine hydrolase (KH) and kynurenine aminotransferase (KATE) in mouse liver, were investigated. Polychlorinated biphenyl (Aroclor 1254) (400mg/kg/day ×4) markedly decreased the activity of both enzymes. Benzo(a)pyrene (BP) and 3‐methylcholanthrene (3‐MC) (40mg/Kg/day ×1) as well as phénobarbital (PB) (75mg/kg/day ×3) did not alter the activity of KH, while that of KATE was mildy reduced. The response of the two enzymes to treatment with chlorpromazine (CPZ) (5mg/Kg/day ×5) were opposite with marked elevation of KH and inhibition of KATE activities. Treatment with B‐naphthoflavone (B‐NF) (80mg/Kg/day ×2), Pyrazole (200mg/Kg/day ×1) or indole (400mg/kg/day ×1) produce no change in the activity of either enzyme. It, seems therefore, that Aroclor(1254) and chlorpromazine may cause disordered kynurenine metabolism through alterations in the activities of its metabolizing enzymes. This, in turn, might affect nicotinamide adenine dinucleotide biosynthesis and/or the accumulation of some tryptophan metabolites suspected of being carcinogenic or co‐carcinogenic.     

1‐Aminobenzotriazole increases glutathione‐s‐transferase activity of maize

Abstract

Glutathione‐S‐transferase (GST) activity of maize (Zea mays L.) seedlings treated with 1‐aminobenzotriazole (ABT) derivatives and/or EPTC were measured using EPTC‐sulfoxide as substrate. Both safeners and ABT derivatives significantly elevated the GST activity in the concentrations needed for effective safening action. ABT is considered as an inhibitor of plant cytochrome P‐450 monooxygenases (P‐450) and, because of this, used to study herbicide mode of action. Our data indicate that ABT has multiple effects on plants influencing not only P‐450 but GST as well. Thus the role of ABT in herbicide metabolism needs reconsideration.     

Diazinon treatment effects on heart and skeletal muscle enzyme activities

Abstract

The effects of low levels of diazinon treatment on four marker enzymes in rat heart and skeletal muscle have been investigated. Adult male Wistar rats were treated twice a week with a dose of 0.5 ml‐kg^‐1day^‐1 diazinon for 28 weeks. Diazinon treated rats gained significantly less weight than Sham‐treated controls. Typical differences in Succinate dehydrogenase (SDH), Lactate dehydrogenase (LDH), Phosphofructo kinase (PFK) and Hexokinase (HK) activities were observed between heart and skeletal muscles. Diazinon feeding had no effect on heart, soleus, gastrocnemius and plantaris SDH, LDH and PFK enzyme activities after 28 weeks. HK activity was significantly increased in sham‐control soieus and plantaris muscles after 28 weeks. Diazinon feeding inhibited HK activity in plantaris muscle after 28 weeks treatment These results demonstrate that chronic low levels of diazinon have little effect on the glycolytic and oxidative activity in heart and skeletal muscle.     

Some toxicological aspects op methamidophos exposure in mice 1

Abstract

Cholinesterase activity in the brain, RBC and plasma of Swiss mice was determined following different routes of administration of methamidophos. Continuous feeding with the insecticide caused a progressive inhibition of both plasma‐ and erythrocyte enzymes. The effect of methamidophos was more pronounced when applied in diet than when administered dermally or intraperitoneally. Following a single injection (i.p.) of methamidophos, the brain enzyme showed maximum inhibition 24 hr following treatment. At the appearance of tremors, the plasma and RBC‐enzymes showed considerable inhibition, the former being more inhibited. The plasma enzyme appears to be the most sensitive enzyme and may be taken as a suitable index for exposure to methamidophos.     

Applications of isotope differentiation for metabolic studies with di‐(2‐ethylhexyl) phthalate

Abstract

The pervasiveness of the plasticizer di‐(2‐ethylhexyl) phthalate (DEHP) in the environment and especially in the laboratory results in a background that may cause severe interference with analytical studies. Animal‐to‐animal variability in the distribution of DEHP metabolites in excreta normally makes it necessary to use large groups of animals when different treatments are compared. Finally, radioactive tracers are usually considered undesirable for metabolic studies involving human subjects. All of these problems can be overcome through the use of muliple isotopic labels, especially ¹²C/¹³C/¹⁴C. Examples are given involving rats and monkeys, and applicability to humans is discussed. The principles involved are not limited to any particular class of test compounds. In rats, the competing pathways for metabolism of phthalate esters produce a different distribution of metabolites from a small intravenous dose of DEHP than from a large oral dose.     

Differential enhanced degradation of cis‐ and trans‐1,3‐D in soil with a history of repeated field applications of 1,3‐D

Abstract

The fumigant 1,3‐dichloropropene (1,3‐D) is considered to be a potential alternative to methyl bromide. The degradation rates of cis‐ and trans‐l,3‐D in soil from a treated site during three successive annual applications of 1,3‐D progressively increased with an increase in the number of annual applications. The enhancement was greater for trans‐l,3‐D degradation than cis‐l,3‐D. In untreated soil, the degradation rates of the two isomers were similar. The enhancement lasted slightly longer than 2 years after annual field application of 1,3‐D had ceased. A single field reapplication of 1,3‐D to the treated site that had not been treated for 2 years resulted in resumed differential enhanced degradation of cis‐ and trans‐l,3‐D. Microorganisms were responsible for the enhanced degradation.     

Azadirachtin induced changes in feeding,dietary utilization and midgut carboxylesterase activity of the final instar larvae of spodoptera litura (fabricius) (lepidoptera: Noctuidae)

Abstract

Final (sixth) instar larvae of Spodoptera litura were fed in increasing amounts of azadirachtin and the effects on feeding activity, dietary utilization and mid‐gut carboxylesterase activity were determined. The antifeedant activity of azadirachtin did not increase in a dose‐dependent manner as reflected by the decline in antifeedant effect at higher doses of 30 and 50 ppm. Dietary concentrations of azadirachtin although significantly lowered the efficiencies of conversion of both ingested (ECI) and digested (ECD) food, it failed to lower the approximate digestibility (AD). The latter however, increased significantly with increasing concentrations of azadirachtin. Feeding of higher doses (30 and 50 ppm) resulted in significant increase in midgut carboxylesterase activity. Thus insensitivity to antifeedant effects and induction of midgut carboxyesterase activity in the older larvae of S.litura In response to high doses of azadirachtin observed in this study can have adverse consequences unless particular attention is paid in developing application strategies for azadirachtin based biopesticides for use in pest control protocols.     

An overview of short‐term tests for the mutagenic and carcinogenic potential of pesticides

Abstract

In the last few years, marked progress has been made in the development of methods for evaluating the mutagenic and carcinogenic potential of pesticide chemicals. The correlation of genetic and related biological activity in short‐term tests with carcinogenic activity in whole animals allows the utilization of short‐term mutagenicity bioassays to prescreen chemicals for effects related to mutation induction and presumptive carcinogenicity. In addition, bioassays now available can measure directly the chemical transformation of normal cells in culture into cells capable of producing tumors when injected into animals.

This paper will review briefly the major types of relevant short‐term tests and will develop a rationale for a phased approach to the evaluation of the mutagenic and carcinogenic potential of environmental chemicals. This approach involves the sequential application of bioassays which are organized into a three‐level matrix emphasizing first detection, then confirmation, and finally hazard assessment. Chemicals demonstrating positive results in the short‐term detection systems and confirmatory bioassays are pursued in higher level whole animal tests. A core battery of tests is proposed to operationally define a negative result. The phased approach should facilitate a cost effective utilization of limited testing resources and provide protection for human health in proportion to the anticipated hazard.

Results obtained in evaluating a series of thirty‐eight pesticide chemicals according to the phased approach are discussed in detail.     

Evaluation of Beta‐naphthoxyacetic Acid for Mutagenic Activity in the Salmonella/mammalian Microsome Assay

1,3‐β‐d‐Glucan derived from baker's yeast was chemically modified in two steps yielding crosslinked carboxymethyl glucan as the sodium salt (2). After cation exchange with hexadecyltrimethylammonium chloride, a hydrophobic adsorbent (3) was obtained which showed an excellent binding of the estrogenic mycotoxin zearalenone with a maximum adsorption of up to 183 mg/g. Compound 3 additionally showed a relatively high adsorption capacity for the trichothecene T‐2 toxin of at least 10 mg/g. Starting from 2, various derivatives were prepared by cation exchange using quaternary ammonium salts bearing substituents besides methyl from four to 18 carbon atoms. The adsorption of T‐2 toxin on these derivatives were compared with compound 3 leading to the conclusion that 3 is the best adsorbent of all investigated tetraalkylammonium‐modified derivatives of 2.