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Monocrotophos is an organophosphate insecticide. 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 subs ...
to birds 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. 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 ...
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 A laboratory rat or lab rat is a brown rat of the subspecies '' Rattus norvegicus domestica'' which is bred and kept for scientific research. While less commonly used for research than mice (see laboratory mouse), rats have served as an impor ...
s were administered 1/50 of dosage of monocrotophos (0.36 mg/kg body weight) orally via gavage daily for three weeks. Animals administered Monocrotophos exhibited mild hyperglycemia and
dyslipidemia Dyslipidemia is an abnormal amount of lipids (e.g. triglycerides, cholesterol and/or fat phospholipids) in the blood. Dyslipidemia is a risk factor for the development of atherosclerotic cardiovascular disease ( ASCVD). ASCVD includes coronary ar ...
in the blood. Cardiac oxidative stress was conferred by accumulation of protein carbonyls, lipid peroxidation and
glutathione Glutathione (GSH, ) 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 such as reactive oxygen species, free radicals, pe ...
production. The cardiac markers (cTn-I, CK-MB and LDH) showed elevated levels in blood plasma, which indicates cardiac tissue damage. The histopathology of the heart tissue authenticated the monocrotophos induced tissue damage by showing signs of nonspecific inflammatory changes and edema 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 (50 ng/ml) induced functional differentiation in PC12 cells has been reported. The studies have been carried out showing mitochondria mediated apoptosis in PC12 cells exposed to monocrotophos. A significant induction in
reactive oxygen species In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen () p ...
,
lipid peroxides Lipid peroxidation is the chain of reactions of oxidative degradation of lipids. It is the process in which free radicals "steal" electrons from the lipids in cell membranes, resulting in cell damage. This process proceeds by a free radical chain ...
, and the ratio of glutathione disulfide/reduced
glutathione Glutathione (GSH, ) 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 such as reactive oxygen species, free radicals, pe ...
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 residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
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 synthesizing a protein. mRNA is created during the ...
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 p ...
,
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, such ...
, BAX,
p53 p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...
, p21, PUMA, and
cytochrome-c The cytochrome complex, or cyt ''c'', is a small hemeprotein found loosely associated with the inner mitochondrial membrane, inner membrane of the mitochondrion. It belongs to the cytochrome c family of proteins and plays a major role in cell apo ...
were significantly
upregulated In the biological context of organisms' production of gene products, downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external stimulus. The complementary pro ...
, whereas the levels of
Bcl-2 Bcl-2 (B-cell lymphoma 2), encoded in humans by the ''BCL2'' gene, is the founding member of the Bcl-2 family of regulator proteins that regulate cell death (apoptosis), by either inhibiting (anti-apoptotic) or inducing (pro-apoptotic) apoptosi ...
,
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 Institut ...
, 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 tr ...
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 DNA laddering is a feature that can observed when DNA fragments, resulting from apoptotic DNA fragmentation, are visualised after separation by gel electrophoresis as first described in 1980 by Andrew Wyllie at the University Edinburgh medical sc ...
, 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 In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...
and mitochondria confirmed the role of monocrotophos in the permeability of the mitochondrial membrane. Mitochondria mediated apoptosis induction was confirmed by the increased activity of caspase cascade. These apoptotic changes could be correlated with elevated levels of expression of selected
cytochrome P450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various co ...
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 ...
/
1A2 The 1A2 Key Telephone System is a business telephone system developed and distributed by the Western Electric, Western Electric Company for the Bell System. The 1A2 Key Telephone System is a modular system that provided flexible solutions for a ...
, 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 Carboxamides Alkene derivatives Pollutants