Inhibitor Report for: Profenofos

Pesticides play an important role in the protection of different crops. Among the diverse sets of pesticides used all over the world, the organophosphates are the most widely used group. Profenofos [O-(4-bromo-2-chlorophenyl) O-ethyl S-propyl phosphorothioate] is one of the most largely used organophosphate insecticides on field crops, vegetables, and fruit crops. The World Health Organization classifies this compound as moderately hazardous (Toxicity Class II), and its residues have been found in vegetables like okra [ (L.) Moench], gooseberries ( sp.), green chilies [ (L.)], curry leaves [ (L.) Spreng], mint leaves [ (L.)], and coriander leaves [ (L.)]. Dietary intake of profenofos (PFF) is the major exposure pathway for humans. When applied to agricultural fields, PFF residues spread into every part of the environment: ambient air, surface water, and soil. In this review, we discuss the worldwide usage of PFF pesticide, its toxic effects on humans and other living organisms in the environment, and biodegradation of this chemical by various microbial strains. To date, no complete biodegradation pathway has been established for PFF pesticide, calling for a study of this nature.

Poisoning signs in chicks administered the organophosphorus insecticide profenofos correlated with in vivo inhibition of brain acetylcholinesterase (AChE) activity. Mixtures of atropine with eserine, pyridinium oximes, or the bispyridinium compound SAD-128 increased the LD50 of coadministered profenofos by up to sevenfold in chicks and fourfold in mice. Atropine and the oximes were less effective as profenofos antidotes, indicating that profenofos-inhibited AChE may undergo rapid aging. Brain AChE from chicks poisoned with profenofos was not reactivated by pralidoxime methanesulfonate, although it was from chicks poisoned with the phosphoramidothiolate, methamidophos. Similarly, eel AChE, inhibited in vitro by bioactivated (-)-profenofos, the most toxic isomer, did not reactivate in contrast to that inhibited by methamidophos, nonbioactivated (-)-profenofos, and (+)-profenofos, with or without bioactivation. It appears that the action of eserine and possibly SAD-128 was due to protecting AChE or cholinergic receptors from profenofos or bioactivated profenofos and that oximes may work in the same way rather than as reactivators due to rapid aging of the inhibited AChE.

Pesticides play an important role in the protection of different crops. Among the diverse sets of pesticides used all over the world, the organophosphates are the most widely used group. Profenofos [O-(4-bromo-2-chlorophenyl) O-ethyl S-propyl phosphorothioate] is one of the most largely used organophosphate insecticides on field crops, vegetables, and fruit crops. The World Health Organization classifies this compound as moderately hazardous (Toxicity Class II), and its residues have been found in vegetables like okra [ (L.) Moench], gooseberries ( sp.), green chilies [ (L.)], curry leaves [ (L.) Spreng], mint leaves [ (L.)], and coriander leaves [ (L.)]. Dietary intake of profenofos (PFF) is the major exposure pathway for humans. When applied to agricultural fields, PFF residues spread into every part of the environment: ambient air, surface water, and soil. In this review, we discuss the worldwide usage of PFF pesticide, its toxic effects on humans and other living organisms in the environment, and biodegradation of this chemical by various microbial strains. To date, no complete biodegradation pathway has been established for PFF pesticide, calling for a study of this nature.

Acylpeptide hydrolase (APH) unblocks N-acetyl peptides. It is a major serine hydrolase in rat blood, brain, and liver detected by derivatization with (3)H-diisopropyl fluorophosphate (DFP) or a biotinylated fluorophosphonate. Although APH does not appear to be a primary target of acute poisoning by organophosphorus (OP) compounds, the inhibitor specificity of this secondary target is largely unknown. This study fills the gap and emphasizes blood APH as a potential marker of OP exposure. The most potent in vitro inhibitors for human erythrocyte and mouse brain APH are DFP (IC(50) 11-17 nM), chlorpyrifos oxon (IC(50) 21-71 nM), dichlorvos (IC(50) 230-560 nM), naled (IC(50) 370-870 nM), and their analogs with modified alkyl substituents. (3)H-diisopropyl fluorophosphate is a potent inhibitor of mouse blood and brain APH in vivo (ED(50) 0.09-0.2 mg/kg and 0.02-0.03 mg/l for ip and vapor exposure, respectively). Mouse blood and brain APH and blood butyrylcholinesterase (BChE) are of similar sensitivity to DFP in vitro and in vivo (ip and vapor exposure), but APH inhibition is much more persistent in vivo (still >80% inhibition after 4 days). The inhibitory potency of OP pesticides in vivo in mice varies from APH selective (dichlorvos, naled, and trichlorfon), to APH and BChE selective (profenofos and tribufos), to ChE selective or nonselective (many commercial insecticides). Sarin administered ip at a lethal dose to guinea pigs inhibits blood acetylcholinesterase and BChE completely but erythrocyte APH only partially. Blood APH activity is therefore a sensitive marker for exposure to some but not all OP pesticides and chemical warfare agents.

Chronic occupational exposure to organophosphorus and carbamate-type pesticides significantly inhibits acetylcholinesterase activity and causes morbidity. This study on mice was designed to evaluate their amino profile and to identify signs of hepatic dysfunction following their chronic exposure to mixtures of organophosphorus pesticides. Laboratory mice were exposed to a formulated mixture of the six organophosphorus pesticides (Dimethoate, Chlorpyrifos, Profenofos, Pirimiphos methyl, Triazophos and Dimethoate) most commonly used in agriculture in this region of the Middle East. Doses (10% of LD50 of the mixture) were given once a week by gavage in corn oil for 7 weeks; the control group was given only corn oil. At the end of the exposure period, mice were culled and blood samples were collected to determine erythrocyte acetylcholinesterase activity, biochemical markers of liver function and concentrations of serum amino acids. Erythrocyte acetylcholinesterase activity and total serum proteins decreased significantly in the exposed group. Serum concentrations of alanine aminotransferase and aspartate aminotransferase, alanine, glutamic acid, glycine, isoleucine, leucine, methionine, ornithine, proline, serine, threonine and valine were significantly increased in the exposed mice, while serum levels of cystine were decreased significantly. There were also non-significant increases in serum alkaline phosphatase, gama-glutamyl transpeptidase and some of the other amino acids. Chronic exposure to mixtures of organophosphorus pesticides is associated with decreased acetylcholinesterase activity, hepatic dysfunction and disturbance of amino acids profile. Biochemical indices of hepatocellular injury and disturbed amino acid metabolism may be of value as markers of chronic exposure to such pesticides.

Succinylcholine is the most important rapid-acting depolarizing muscle relaxant during anesthesia. Its desirable short duration of action is controlled by butyrylcholinesterase, the detoxifying enzyme. There are two reported cases of prolonged paralysis from succinylcholine in patients poisoned with the organophosphorus insecticides parathion and chlorpyrifos. The present study examines the possibility that other organophosphorus and methylcarbamate pesticides might also prolong succinylcholine action by inhibiting butyrylcholinesterase using mice treated intraperitoneally as a model and relating inhibition of blood serum hydrolysis of butyrylthiocholine to potentiated toxicity (mouse mortality). The organophosphorus plant defoliant tribufos (4 h pretreatment, 160 mg/kg) and organophosphorus plant growth regulator ethephon (1 h pretreatment, 200 mg/kg) potentiate the toxicity of succinylcholine by seven- and fourfold, respectively. Some other pesticides or analogs are more potent sensitizers for succinylcholine toxicity with threshold levels of 0.5, 1.0, 1.7, 8, 10, and 67 mg/kg for phenyl saligenin cyclic phosphonate, profenofos, methamidophos, tribufos, chlorpyrifos, and ethephon, respectively. Enhanced mortality from succinylcholine is generally observed when serum butyrylcholinesterase is inhibited 55-94%. Mivacurium, a related nondepolarizing muscle relaxant also detoxified by butyrylcholinesterase, is likewise potentiated by at least threefold on 4 hour pretreatment with tribufos (25 mg/kg) or profenofos (10 mg/kg).

Poisoning signs in chicks administered the organophosphorus insecticide profenofos correlated with in vivo inhibition of brain acetylcholinesterase (AChE) activity. Mixtures of atropine with eserine, pyridinium oximes, or the bispyridinium compound SAD-128 increased the LD50 of coadministered profenofos by up to sevenfold in chicks and fourfold in mice. Atropine and the oximes were less effective as profenofos antidotes, indicating that profenofos-inhibited AChE may undergo rapid aging. Brain AChE from chicks poisoned with profenofos was not reactivated by pralidoxime methanesulfonate, although it was from chicks poisoned with the phosphoramidothiolate, methamidophos. Similarly, eel AChE, inhibited in vitro by bioactivated (-)-profenofos, the most toxic isomer, did not reactivate in contrast to that inhibited by methamidophos, nonbioactivated (-)-profenofos, and (+)-profenofos, with or without bioactivation. It appears that the action of eserine and possibly SAD-128 was due to protecting AChE or cholinergic receptors from profenofos or bioactivated profenofos and that oximes may work in the same way rather than as reactivators due to rapid aging of the inhibited AChE.