Monocrotophos is an

organophosphate In organic chemistry, organophosphates (also known as phosphate esters, or OPEs) are a class of organophosphorus compounds with the general structure , a central phosphate molecule with alkyl or aromatic substituents. They can be considered ...

insecticide Insecticides are pesticides used to kill insects. They include ovicides and larvicides used against insect eggs and larvae, respectively. The major use of insecticides is in agriculture, but they are also used in home and garden settings, i ...

. It is acutely

toxic Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subst ...

birds Birds are a group of warm-blooded vertebrates constituting the class (biology), class Aves (), characterised by feathers, toothless beaked jaws, the Oviparity, laying of Eggshell, hard-shelled eggs, a high Metabolism, metabolic rate, a fou ...

and humans, so it has been banned in the U.S., the E.U., India and many other countries.

Uses

Monocrotophos is principally used in agriculture, as a relatively cheap pesticide. However, it is also used frequently as a tool to commit

suicide Suicide is the act of intentionally causing one's own death. Risk factors for suicide include mental disorders, physical disorders, and substance abuse. Some suicides are impulsive acts driven by stress (such as from financial or ac ...

. It is used as a pesticide for cucumber. Monocrotophos is believed to be the contaminant responsible for the death of 23 schoolchildren in a Bihar, India school. They ate a state-provided school lunch in the district of Saran in India in July 2013 which was prepared in oil kept in the container of this pesticide.

Toxicity

To wildlife

Widespread bird kills, including a large kill of

Swainson's Hawk Swainson's hawk (''Buteo swainsoni'') is a large bird species in the Accipitriformes order. This species was named after William Swainson, a British naturalist. It is colloquially known as the grasshopper hawk or locust hawk, as it is very fond o ...

s in Argentina, have resulted from the use of monocrotophos.

Diabetogen

In a study published in Genome Biology, researchers demonstrated the gut microbiota mediated diabetogenic effect of organophosphate insecticides. They used monocrotophos as the prototypical organophosphate in their study and showcased that during chronic intake, monocrotophos is degraded by the gut microbiota and the end products are converted to glucose via gluconeogenesis that account for glucose intolerance. All the studies were validated in human samples from the villages in Madurai.

Cardiotoxicity

In a recent study,

Wistar rat Laboratory rats or lab rats are strain (biology), strains of the rat subspecies ''Rattus norvegicus domestica'' (Domestic Norwegian rat) which are bred and kept for scientific research. While Animal testing on rodents, less commonly used for re ...

s were administered 1/50 of dosage of monocrotophos (0.36 mg/kg body weight) orally via

gavage Force-feeding is the practice of feeding a human or animal against their will. The term ''gavage'' (, , ) refers to supplying a substance by means of a small plastic feeding tube passed through the nose (nasogastric tube, nasogastric) or mouth (o ...

daily for three weeks. Animals administered Monocrotophos exhibited mild

hyperglycemia Hyperglycemia is a condition where unusually high amount of glucose is present in blood. It is defined as blood glucose level exceeding 6.9 mmol/L (125 mg/dL) after fasting for 8 hours or 10 mmol/L (180 mg/dL) 2 hours after eating. Blood gluc ...

and

dyslipidemia Dyslipidemia is a metabolic disorder characterized by abnormally high or low amounts of any or all lipids (e.g. fats, triglycerides, cholesterol, phospholipids) or lipoproteins in the blood. Dyslipidemia is a risk factor for the development of ...

in the blood. Cardiac oxidative stress was conferred by accumulation of protein carbonyls,

lipid peroxidation Lipid peroxidation, or lipid oxidation, is a complex chemical process that leads to oxidative degradation of lipids, resulting in the formation of peroxide and hydroperoxide derivatives.{{Cite journal , last1=Ayala , first1=Antonio , last2=Muñoz ...

and

glutathione Glutathione (GSH, ) is an organic compound with the chemical formula . It is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources ...

production. The cardiac markers (cTn-I, CK-MB and LDH) showed elevated levels in blood plasma, which indicates cardiac tissue damage. The

histopathology Histopathology (compound of three Greek words: 'tissue', 'suffering', and '' -logia'' 'study of') is the microscopic examination of tissue in order to study the manifestations of disease. Specifically, in clinical medicine, histopatholog ...

of the heart tissue authenticated the monocrotophos induced tissue damage by showing signs of nonspecific inflammatory changes and

edema Edema (American English), also spelled oedema (British English), and also known as fluid retention, swelling, dropsy and hydropsy, is the build-up of fluid in the body's tissue (biology), tissue. Most commonly, the legs or arms are affected. S ...

between muscle fibres. Thus the findings of this preliminary study illustrate the cardiotoxic effect of prolonged monocrotophos intake in rats and suggest that MCP can be a possible independent and potent environmental cardiovascular risk factor.

Acute effects

Nerve growth factor Nerve growth factor (NGF) is a neurotrophic factor and neuropeptide primarily involved in the regulation of growth, maintenance, proliferation, and survival of certain target neurons. It is perhaps the prototypical growth factor, in that it was ...

(50 ng/ml) induced functional differentiation in

PC12 cells PC12 is a Cell culture#Common cell lines, cell line derived from a pheochromocytoma of the rat adrenal medulla, that have an Embryonic stem cell, embryonic origin from the neural crest that has a mixture of neuroblast, neuroblastic cells and eosin ...

has been reported. The studies have been carried out showing

mitochondria A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...

mediated

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

in PC12 cells exposed to monocrotophos. A significant induction in

reactive oxygen species In chemistry and biology, reactive oxygen species (ROS) are highly Reactivity (chemistry), reactive chemicals formed from diatomic oxygen (), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (H2O2), superoxide (O2−), hydroxyl ...

lipid peroxides Lipid peroxidation, or lipid oxidation, is a complex chemical process that leads to oxidative degradation of lipids, resulting in the formation of peroxide and hydroperoxide derivatives.{{Cite journal , last1=Ayala , first1=Antonio , last2=Muñoz ...

, and the ratio of

glutathione disulfide Glutathione disulfide (GSSG) is a disulfide derived from two glutathione molecules. In living cells, glutathione disulfide is reduced into two molecules of glutathione with reducing equivalents from the coenzyme NADPH. This reaction is catalyzed ...

/reduced

was observed in cells exposed to selected doses of monocrotophos. Following the exposure of PC12 cells to monocrotophos, the levels of

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

and

mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...

expression of

caspase-3 Caspase-3 is a caspase protein that interacts with caspase-8 and caspase-9. It is encoded by the ''CASP3'' gene. ''CASP3'' orthologs have been identified in numerous mammals for which complete genome data are available. Unique orthologs are also ...

caspase-9 Caspase-9 is an enzyme that in humans is encoded by the ''CASP9'' gene. It is an initiator caspase, critical to the apoptotic pathway found in many tissues. Caspase-9 homologs have been identified in all mammals for which they are known to exist, ...

, BAX,

p53 p53, also known as tumor protein p53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory transcription factor protein that is often mutated in human cancers. The p53 proteins (originally thou ...

p21 p21Cip1 (alternatively p21Waf1), also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin-dependent kinase inhibitor (CKI) that is capable of inhibiting all cyclin/ CDK complexes, though is primarily associ ...

, PUMA, and cytochrome-c were significantly upregulated, whereas the levels of

Bcl-2 Bcl-2, encoded in humans by the ''BCL2'' gene, is the founding member of the Bcl-2 family of regulator proteins. BCL2 blocks programmed cell death (apoptosis) while other BCL2 family members can either inhibit or induce it. It was the first a ...

Bcl-w Bcl-2-like protein 2 is a 193-amino acid protein that in humans is encoded by the ''BCL2L2'' gene on chromosome 14 ( band q11.2-q12). It was originally discovered by Leonie Gibson, Suzanne Cory and colleagues at the Walter and Eliza Hall Instit ...

, and

Mcl-1 Induced myeloid leukemia cell differentiation protein Mcl-1 is a protein that in humans is encoded by the ''MCL1'' gene. Function The protein encoded by this gene belongs to the Bcl-2 family. Alternative splicing occurs at this locus and two t ...

were downregulated.

TUNEL assay Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) is a method for detecting DNA fragmentation by labeling the 3′- hydroxyl termini in the double-strand DNA breaks generated during apoptosis. Method TUNEL is a method for dete ...

, DNA laddering, and micronuclei induction show that long-term exposure of PC12 cells to monocrotophos at higher concentration (10⁻⁵ M) decreases the number of apoptotic events due to an increase in the number of necrotic cells. Monocrotophos-induced translocation of BAX and cytochrome-c proteins between the

cytoplasm The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell a ...

and mitochondria confirmed the role of monocrotophos in the permeability of the

mitochondrial membrane A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used ...

. Mitochondria mediated apoptosis induction was confirmed by the increased activity of

caspase Caspases (cysteine-aspartic proteases, cysteine aspartases or cysteine-dependent aspartate-directed proteases) are a family of protease enzymes playing essential roles in programmed cell death. They are named caspases due to their specific cyste ...

cascade. These apoptotic changes could be correlated with elevated levels of expression of selected

cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

s (

CYP1A1 Cytochrome P450, family 1, subfamily A, polypeptide 1 is a protein that in humans is encoded by the ''CYP1A1'' gene. The protein is a member of the cytochrome P450 superfamily of enzymes. Function Metabolism of xenobiotics and drugs CYP1A1 is ...

/ 1A2, 2B1/2B2, 2E1) in PC12 cells exposed to monocrotophos (10⁻⁵ M).Monocrotophos Induced Apoptosis in PC12 Cells: Role of Xenobiotic Metabolizing Cytochrome P450s
/ref>

References

External links

* {{Acetylcholine metabolism and transport modulators Acetylcholinesterase inhibitors Organophosphate insecticides Acrylamides Pollutants