Impacts of organophosphate pesticide types and concentrations on aquatic bacterial communities and carbon cycling.

Organophosphorus pesticides (OPPs) are important chemical stressors in aquatic ecosystems, and they attract increasing more attentions recently. However, the impacts of different OPPs on carbon cycling remain unclear, particularly for those functional-yet-uncultivable microbes. This study investigated the change in lake aquatic microbial communities in the presence of dichlorvos, monocrotophos, omethoate and parathion. All OPPs significantly inhibited biomass (p < 0.05) and the expression of carbon cycle-related cbbLG gene (p < 0.01), and altered aquatic microbial community structure, interaction, and assembly. Variance partitioning analysis showed a stronger impact of pesticide type on microbial biomass and community structure, where pesticide concentration played more significant roles in carbon cycling. From analysis of cbbLG gene and PICRUSt2, Luteolibacter and Verrucomicrobiaceae assimilated inorganic carbon through Wood-Ljungdahl pathway, whereas it was Calvin-Benson-Bassham cycle for Cyanobium PCC-6307. This work provides a deeper insight into the behavior and mechanisms of microbial community change in aquatic system in response to OPPs, and explicitly unravels the impacts of OPPs on their carbon-cycling functions.

Microbial detoxification of chlorpyrifos, profenofos, monocrotophos, and dimethoate by a multifaceted rhizospheric Bacillus cereus strain PM38 and its potential for the growth promotion in cotton.

Bacillus genera, especially among rhizobacteria, are known for their ability to promote plant growth and their effectiveness in alleviating several stress conditions. This study aimed to utilize indigenous Bacillus cereus PM38 to degrade four organophosphate pesticides (OPs) such as chlorpyrifos (CP), profenofos (PF), monocrotophos (MCP), and dimethoate (DMT) to mitigate the adverse effects of these pesticides on cotton crop growth. Strain PM38 exhibited distinct characteristics that set it apart from other Bacillus species. These include the production of extracellular enzymes, hydrogen cyanide, exopolysaccharides, Indol-3-acetic acid (166.8 µg/mL), siderophores (47.3 µg/mL), 1-aminocyclopropane-1-carboxylate deaminase activity (32.4 µg/mL), and phosphorus solubilization (162.9 µg/mL), all observed at higher concentrations. This strain has also shown tolerance to salinity (1200 mM), drought (20% PEG-6000), and copper and cadmium (1200 mg/L). The amplification of multi-stress-responsive genes, such as acdS, ituC, czcD, nifH, sfp, and pqqE, further confirmed the plant growth regulation and abiotic stress tolerance capability in strain PM38. Following the high-performance liquid chromatography (HPLC) analysis, the results showed striking compatibility with the first kinetic model. Strain PM38 efficiently degraded CP (98.4%), PF (99.7%), MCP (100%), and DMT (95.5%) at a concentration of 300 ppm over 48 h at 35 °C under optimum pH conditions, showing high coefficients of determination (R2) of 0.974, 0.967, 0.992, and 0.972, respectively. The Fourier transform infrared spectroscopy (FTIR) analysis and the presence of opd, mpd, and opdA genes in the strain PM38 further supported the potential to degrade OPs. In addition, inoculating cotton seedlings with PM38 improved root length under stressful conditions. Inoculation of strain PM38 reduces stress by minimizing proline, thiobarbituric acid-reactive compounds, and electrolyte leakage. The strain PM38 has the potential to be a good multi-stress-tolerant option for a biological pest control agent capable of improving global food security and managing contaminated sites.

Toxic effects of organophosphate pesticide monocrotophos in aquatic organisms: A review of challenges, regulations and future perspectives.

In recent times, usage of pesticide, herbicides and synthetic fertilizers in farming lands has made the environment worse. The pesticide residues and toxic byproducts from agricultural lands were found to contaminate the aquatic ecosystem. The misuse of synthetic pesticide not only affects the environment, but also affects the health status of aquatic organisms. The organophosphate pesticide pollutants are emerging contaminants, which threatens the terrestrial and aquatic ecosystem. Monocrotophos (MCP) is an organophosphate insecticide, utilized on crops including rice, maize, sugarcane, cotton, soybeans, groundnuts and vegetables. MCP is hydrophilic in nature and their solubilizing properties reduce the soil sorption which leads to groundwater contamination. The half-life period of MCP is 17-96 and the half-life period of technical grade MCP is 2500 days if held stable at 38 °C in a container. MCP causes mild to severe confusion, anxiety, hyper-salivation, convulsion and respiratory distress in mammals as well as aquatic animals. The MCP induced toxicity including survival rate, behavioural changes, reproductive toxicity and genotoxicity in different aquatic species have been discussed in this review. Furthermore, the ultimate aim of this review is to highlight the international regulations, future perspectives and challenges involved in using the MCP.

DNA Methylation Profiling of Ovarian Tissue of Climbing Perch (Anabas testudienus) in Response to Monocrotophos Exposure.

Epigenetic modifications like DNA methylation can alter an organism's phenotype without changing its DNA sequence. Exposure to environmental toxicants has the potential to change the resilience of aquatic species. However, little information is available on the dynamics of DNA methylation in fish gonadal tissues in response to organophosphates. In the present work, reduced-representation bisulfite sequencing was performed to identify DNA methylation patterns in the ovarian tissues of Anabas testudienus exposed to organophosphates, specifically monocrotophos (MCP). Through sequencing, an average of 41,087 methylated cytosine sites were identified and distributed in different parts of genes, i.e., in transcription start sites (TSS), promoters, exons, etc. A total of 1058 and 1329 differentially methylated regions (DMRs) were detected as hyper-methylated and hypo-methylated in ovarian tissues, respectively. Utilizing whole-genome data of the climbing perch, the DMRs, and their associated overlapping genes revealed a total of 22 genes within exons, 45 genes at transcription start sites (TSS), and 218 genes in intergenic regions. Through gene ontology analysis, a total of 16 GO terms particularly involved in ovarian follicular development, response to oxidative stress, oocyte maturation, and multicellular organismal response to stress associated with reproductive biology were identified. After functional enrichment analysis, relevant DMGs such as steroid hormone biosynthesis (Cyp19a, 11-beta-HSD, 17-beta-HSD), hormone receptors (ar, esrrga), steroid metabolism (StAR), progesterone-mediated oocyte maturation (igf1ar, pgr), associated with ovarian development in climbing perch showed significant differential methylation patterns. The differentially methylated genes (DMGs) were subjected to analysis using real-time PCR, which demonstrated altered gene expression levels. This study revealed a molecular-level alteration in genes associated with ovarian development in response to chemical exposure. This work provides evidence for understanding the relationship between DNA methylation and gene regulation in response to chemicals that affect the reproductive fitness of aquatic animals.

Degradation of mevinphos and monocrotophos by OH radicals in the environment: A computational investigation on mechanism, kinetic, and ecotoxicity.

Known organophosphorus pesticides are used widely in agriculture to improve the production of crops. Based on the literature, the degradation of some organophosphorus pesticides was studied theoretically. However, the mechanisms and variation of toxicity during the degradation of mevinphos and monocrotophos are still unclear in the environment, especially in wastewater. In this study, the reaction mechanisms for the degradation of the two representative organophosphorus pesticides (i.e., mevinphos and monocrotophos) in presence of OH radicals in the atmosphere and water are proposed using quantum chemical methods wB97-XD/6-311 + +G(3df,2pd)//wB97-XD/6-311 + +G(d,p). Result shows that the dominant channel is OH-addition to the C atom in CC bond with energy barriers being 15.6 and 14.7 kJ/mol, in the atmosphere and water, respectively, for mevinphos. As for monocrotophos, H-abstraction from NH group via barriers of 8.2 and 10.6 kJ/mol is more feasible in both the atmosphere and water. Moreover, the subsequent reactions of the major products in the atmosphere with NO and O2 were also studied to evaluate the atmospheric chemistry of mevinphos and monocrotophos. Kinetically, the total rate constant is 2.68 × 10-9 and 3.86 × 10-8 cm3 molecule-1·s-1 for mevinphos and monocrotophos in the atmosphere and 4.91 × 1010 and 7.77 × 1011 M-1 s-1 in the water at 298 K, thus the lifetime is estimated to be 36.46-364.60 s (2.53-25.31 s) in the atmosphere, and 1.41 × 10-2 - 1.41 × 10-1 s (8.92 ×10-4 - 8.92 ×10-3 s) in the advanced oxidation processes (AOPs) system. Furthermore, ecotoxic predictions for rats and three aqueous organisms imply their toxicity are reduced during degradation by using ECOSAR and T.E.S.T program based quantitative structure and activity relationship (QSAR) method.

Neuroprotective Effect of N-acetylcysteine Against Monocrotophos-Induced Oxidative Stress in Different Brain Regions of Rats.

Monocrotophos (MCP) is systemic organophosphate insecticide used against crop pests. It is reported to cause mammalian toxicity through both acute and chronic exposure. In the present study, we have shown the protective role of N-acetylcysteine (NAC) against MCP-induced oxidative stress in frontal cortex, corpus striatum and hippocampus brain regions of rats. Male Albino Wistar rats were divided into control, NAC-treated, MCP and NAC + MCP-treated groups. An oral dose of MCP (0.9 mg/kg b.wt) and NAC (200 mg/kg b.wt) was administered for 28 days. Results showed an increase in lipid peroxidation (LPO) and protein oxidation followed by decreased antioxidant enzymes after 28 days of MCP exposure. Histopathological analysis showed that monocrotophos exposure caused neurodegenerative changes as evident by neurons with dystrophic changes in the form of shrunken hyperchromatic nuclei in all the regions of the rat brain. N-acetylcysteine supplementation to MCP-treated rats showed a reduction in oxidative stress and ameliorated cellular alterations in all of the three regions. The results of the study indicate that N-acetylcysteine offers neuroprotection by improving antioxidant response and decreasing oxidative stress in different regions of the rat brain.

N-acetylcysteine ameliorates monocrotophos exposure-induced mitochondrial dysfunctions in rat liver.

Background: Monocrotophos (MCP) is an organophosphate pesticide with well-known toxicity in mammals. Exposure of MCP is associated with altered molecular physiology at sub-cellular levels. This study investigated the efficacy of N-acetylcysteine (NAC) against MCP exposure mediated mitochondrial dysfunctions in hepatic tissue of rats.Methods: Male Wistar rats were given NAC (200 mg/kg b.wt), MCP (0.9 mg/kg b.wt) and NAC together with MCP, intragastrically for 28 consecutive days. Mitochondrial complexes activities were evaluated using biochemical analysis. mRNA expression of mitochondrial complexes subunits, PGC-1α and its downstream regulators were analyzed using polymerase chain reaction.Results: Exposure of MCP (0.9 mg/kg b.wt, intragastrically, 28 d) decreased mitochondrial complexes activities and gene expression of complexes subunits. The expression of PGC-1α, NRF-1, NRF-2, and Tfam was also reduced significantly. The administration of NAC (200 mg/kg b.wt, intragastrically, 28 d) significantly increased mitochondrial complexes activities and gene expression of complexes subunits. Additionally, NAC also maintained mitochondrial functions, and enhanced the gene expression of PGC-1α and its downstream regulators.Conclusion: The results of this study indicate that NAC prevents hepatic mitochondrial dysfunctions and maintains PGC-1α signaling. In conclusion, NAC might be speculated as a therapeutic agent for mitochondrial dysfunctions following toxic exposures.

Ultrastructural studies of photoreceptor cell degeneration with organophosphate and its regeneration in Cyprinus carpio communis L.

Organophosphates are highly neurotoxic to aquatic fauna if they enter the water bodies as runoff, thus affecting the nervous system of the fishes. The present study was undertaken to investigate the vision changes, especially on the photoreceptor layer of the retina, of Cyprinus carpio communis L. when exposed to monocrotophos, an organophosphate. Fish were exposed to three sub-lethal concentrations of LC50, i.e. 0.038 ppm (1/10 LC50), 0.062 ppm (1/6 LC50), and 0.126 ppm (1/3 LC50), to observe the changes in the photoreceptor cells at the behavioral, histopathological and ultrastructural levels. Further, acetylcholinesterase activity was also evaluated. Behavioral changes, such as long resting period, inactivity, increase in air gulps and decrease in opercular and fin movements, were observed. A semi-quantitative analysis of the histological sections showed shrinkage in retinal layers at 0.038 ppm concentration of monocrotophos. At 0.062 ppm, the disappearance of the outer nuclear layer was observed and at the highest concentration of 0.126 ppm, damage in all retinal layers involving necrosis of the outer segment of the photoreceptor cells was observed. Further, at the ultrastructural level, detachment of photoreceptor cells and damage in the inner and outer segments of the photoreceptors were observed in an increasing dose-dependent manner. A reduction in the acetylcholinesterase level was observed in the treated groups. The treated fish were then transferred to toxicant-free water for 60 days to study self-regeneration, but no regeneration was observed in photoreceptor cells of the fish retina. This study shows that exposure to of monocrotophos effectively damages and disturbs the functioning of photoreceptor cells of retina of C. carpio communis L., thus affecting its vision.

Polyvinylchloride and polypropylene as adsorbents of the pesticide monocrotophos enhance oxidative stress in Eudrillus eugeniae (Kinberg).

The use of plastics has increased significantly with consequent rise in the generation of wastes. Microplastics (MPs) with particle size <5 mm are produced in natural terrestrial habitats by weathering of the discarded plastic debris and therefore are likely to impact soil biota. Earthworms are the dominant soil fauna which play vital role in soil formation and decomposition of organics. Since these animals are soil feeders, MP particles contaminating soil are likely to enter in to the gut of these animals affecting their physiology. MPs have been shown to be potent adsorbents of various other pollutants such as heavy metals and agrochemicals. This study reports the effects of two MPs, polyvinyl chloride (PVC) and polypropylene (PP) alone and in combination with the pesticide monocrotophos in soil on tissue protein, lipid peroxidation (LPX), activities of lactate dehydrogenase (LDH) and catalase (CAT) of an epigeic earthworm Eudrillus eugeniae over an exposure period of 48h. Results from molecular docking and laboratory experiment confirmed that both the MPs are potent adsorbents of the pesticide and enhanced oxidative stress on the animal with significant reduction in protein, increased LPX level and enzyme activities. PP indicated significantly higher pesticide adsorption relative to PVC.

DNA damage and biochemical responses in estuarine bivalve Donax incarnatus (Gmelin, 1791) exposed to sub-lethal concentrations of an organophosphate pesticide monocrotophos.

Monocrotophos (MCP) is a highly toxic and broad-spectrum pesticide extensively used for agricultural and household purposes. The present study was aimed to evaluate the genotoxicity and alterations in the biochemical and physiological conditions induced by monocrotophos in a non-target organism, an estuarine bivalve, Donax incarnatus. The bivalves were exposed to three sub-lethal concentrations (6.8, 13.7, and 27.45 ppm) of MCP for a period of 72 h. DNA damage was assessed using the comet assay. Oxidative stress was analyzed using catalase, glutathione peroxidase, and superoxide dismutase. Neurotoxicity was evaluated using the acetylcholinesterase assay (AChE) and the physiological condition was assessed using the condition index (CI). A significant concentration-dependent increase of DNA damage was observed as well as a decline in the activities of the antioxidant enzymes. However, a decrease in DNA damage was observed with advancing time. A significant decrease of AChE activity and CI was observed in the bivalves exposed to MCP. Positive correlations were also observed between DNA damage and the antioxidant enzymes whereas negative correlations were observed between AChE and the antioxidant enzymes indicating MCP toxicity mediated by oxidative stress.

Toxicity and detoxification of monocrotophos from ecosystem using different approaches: A review.

Monocrotophos (MCP) is an organophosphate insecticide with broad application in agricultural crops like rice, maize, sugarcane, cotton, soybeans, groundnut and vegetables. MCP solubilize in water readily and thus reduced sorption occurs in soil. This leads to MCP leaching into the groundwater and pose a significant threat of contamination. The MCP's half-life depends on the temperature and pH value and estimated as 17-96 d. But the half-life of technical grade MCP can exceed up to 2500 days if properly stored at 38 °C in a glass or polyethylene container in a stable condition. It causes abnormality, ranging from mild to severe confusion, agitation, hypersalivation, convulsion, pulmonary failure, senescence in mammals and insects. MCP affects humans by inhibiting the activity of the acetylcholine esterase enzyme. MCP is accountable for the catalytic degradation of acetylcholine and affects the neurotransmission between neurons. This review discusses MCP's various aspects and fate on aquatic and terrestrial life forms, quantification methods for monitoring, various degradation processes, and their mechanisms. Different case studies related to its impact on the human population in different parts of the world have been discussed. Efforts have also been made to summarize and present different microbial population's role in its degradation and mineralization.

Effects of in vitro exposure of perfluorooctanoic acid and monocrotophos on astroglia SVG p12 cells.

Glia cells provide supportive functions to the central nervous system and can be compromised by environmental contaminants. The primary objective of this study was to characterize the effects of in vitro exposure to perfluorooctanoic acid, a persistent environmental contaminant and/or monocrotophos (MCP), a neurotoxic organophosphate that is rapidly metabolized, to astroglia SVG p12 cells. The endpoints evaluated include cell viability, intracellular glutamate levels as a marker of astrocyte homeostasis function, differential gene expression for selected proteins, which include inflammatory markers (tachykinin), astrocytosis (nestin), S100B, and metabolism enzymes (CYP1A1). The results from cell viability revealed significant differences from the controls at some of the concentrations tested. Also, intracellular glutamate levels were elevated at the 10-µM concentration for perfluorooctanoic acid (PFOA) as well as the 10-µM PFOA/5-µM MCP concentration. Gene expression results at 80-µM PFOA concentration revealed a significant increase in the expression of S100B, tachykinin and CYP1A1. A combination of 10-µM PFOA/20-µM MCP caused a significant decrease in the expression of tachykinin. Gene expression for MCP exposures produced a decrease at the 20-µM MCP concentration. Immunofluorescence results indicated an increase in nestin protein expression for the 20-µM concentration of MCP, which contradicted the gene expression at the same concentration tested. The results indicate that toxicity to glia cells can compromise critical glia functions and could be implicated in neurodegenerative diseases.

Monocrotophos, an organophosphorus insecticide, induces cortical and trabecular bone loss in Swiss albino mice.

Till now monocrotophos (MCP) has been addressed as a neurotoxic stressor. Limited studies investigate its aftermath on bone pathologies. Given the fact that MCP is a propensely used insecticide in developing countries, this study investigates its potential to mirror osteoporotic features and bone loss incurred in a rodent model. Briefly, Swiss albino mice were orally gavaged daily with varying doses of MCP for 8 weeks. Musculoskeletal changes were analyzed through micro-computed tomography and histology. A series of in vitro and ex vivo cell culture experiments were performed on MC3T3E-1 and primary osteoclast cultures. Results highlight that oral gavaging with MCP causes bone loss from the cortico-trabecular interface by decreasing the osteoblast and increasing the osteoclast number. Results from in vitro studies establish that MCP treatment increases the TRAP-positive multinucleated cell number during osteoclast differentiation. Ex-vivo experiments with MCP-treated animal sera further substantiate the in vivo claims with significant decreases seen in cell viability, proliferation, mineralization and differentiation studies. In conclusion MCP induces osteoclastogenesis (bone loss) on direct stimulation and alters the circulating factors in MCP-treated serum. Holistically, this work would be of potential significance to patients suffering from pesticide induced osteoporosis.

Deregulation of hepatic lipid metabolism associated with insulin resistance in rats subjected to chronic monocrotophos exposure.

In our previous study, we demonstrated the potential of monocrotophos (MCP), an organophosphorus insecticide (OPI), to induce glucose intolerance, insulin resistance (IR), and dyslipidemia with hyperinsulinemia in rats after chronic exposure. As hyperinsulinemia is likely to exert an impact on hepatic lipid metabolism, we carried out this study to establish the effect of chronic MCP exposure (0.9 and 1.8 mg/kg/day for 180 days) on hepatic lipid metabolism in rats. The state of IR induced by MCP in rats was associated with an increase in the liver lipid content (triglyceride and cholesterol) and expression levels of sterol regulatory element-binding proteins, PPARγ, acetyl-CoA carboxylase, and fatty acid synthase in the liver. Similarly, activities of key enzymes (acetyl-COA carboxylase, fatty acid synthase, lipin 1, malic enzyme, glucose-6-phosphate dehydrogenase, and glycerol-3-phosphate dehydrogenase), which regulate lipogenesis, were enhanced in livers of pesticide-treated rats. A strong correlation was observed between insulin levels, hepatic lipid content, and plasma lipid profile in treated rats. Our study suggests that long-term exposure to OPIs not only has a propensity to induce a state of hyperinsulinemic IR, but it is also associated with augmented hepatic lipogenesis, which may explain dyslipidemia induced by chronic exposure to MCP.

Effect of chronic exposure to monocrotophos on white adipose tissue in rats and its association with metabolic dyshomeostasis.

Earlier, we demonstrated that chronic exposure to monocrotophos (MCP) elicits insulin resistance in rats along with increased white adipose tissue (WAT) weights. This study was carried out to delineate the biochemical and molecular changes in adipose tissues of rats subjected to chronic exposure to MCP (0.9 and 1.8 mg/kg bw/d for 180 days). Pesticide-treated rats exhibited increased fasting glucose and hyperinsulinemia as well as dyslipidemia. Tumor necrosis factor-alpha and leptin levels were elevated, while adiponectin level was suppressed in plasma of treated rats. MCP treatment caused discernable increase in the weights of perirenal and epididymal WAT. Acetyl coenzyme A carboxylase, fatty acid synthase, glyceraldehyde-3-phosphate dehydrogenase, lipin-1, and lipolytic activities were elevated in the WAT of MCP-treated rats. Corroborative changes were observed in the expression profile of proteins that are involved in lipogenesis and adipose tissue differentiation. Our results clearly demonstrate that long-term exposure to organophosphorus insecticides (OPIs) such as MCP has far-reaching consequences on metabolic health as evidenced by the association of adipogenic outcomes with insulin resistance, hyperinsulinemia, endocrine dysregulations, and dyslipidemia. Taken together, our results suggest that long-term exposure to OPI may be a risk factor for metabolic dysregulations.

Establishment of resveratrol and its derivatives as neuroprotectant against monocrotophos-induced alteration in NIPBL and POU4F1 protein through molecular docking studies.

Monocrotophos (MCP) is a broad spectrum organophosphorus insecticide, which is widely used as foliar spray to the different important crops. MCP may reach the soil and the aquatic environment directly or indirectly during and after the application, which leads to the different environmental issues. MCP is found to be associated with neurotoxicity and its toxic effects have been monitored during different stages of neuronal development. Identification of gene expression in MCP-induced neurotoxicity during neuronal developmental stage is a major area of genomic research interest. In accordance with this identification, screening of potential neuroprotective, natural resources are also required as a preventive aspects by targeting the impaired genes. In this current course of work, microarray experiment has been used to identify genes that were expressed in monocrotophos (MCP)-induced mesenchymal stem cells (MSC) and also the neuroprotectant activity of RV on MCP-exposed MSCs. Microarray experiment data have been deposited in NCBI's Gene Expression Omnibus database and are accessible through GEO Series accession number GSE121261. In this paper, we have discussed two important genes NIPBL (nipped-B-like protein) and POU4F1 (POU domain, class 4, transcription factor 1). These genes were found to be significantly expressed in MCP-exposed MSC and show minimum expression in presence of RV. Homology modelling and docking study was done to identify the interaction and binding affinity of resveratrol and its derivatives with NIPBL and POU4F1 protein. Docking analysis shows that RV and its derivatives have strong interaction with NIPBL and POU4F1 protein hence proves the significance of resveratrol as potential neuroprotectant. This paper highlights the hazardous impact of MCP on neuronal development disorders and repairing potentiality of RV and its derivatives on altered genes involved in neuronal diseases. Graphical Abstract.

Fatal monocrotophos poisoning by cutaneous absorption while sleeping: A remarkable case study.

Organophosphate poisoning is a continued menace associated with high morbidity and mortality in both resource-crunched developing and developed countries. Cases have been described of deliberate self-poisoning which has higher mortality than accidental exposure. Fatal poisoning by accidental dermal absorption is rarely reported for monocrotophos. Authors detail fatal accidental monocrotophos poisoning in adult female by dermal exposure while sleeping. Pesticide was detected in post-mortem blood and skin by chromatography and spectroscopy. Extraction along with review of literature for monocrotophos poisoning is adjuncted in this study.

Quantitative analysis of in-vivo responses of reproductive and thyroid endpoints in male goldfish exposed to monocrotophos pesticide.

Cross-regulation occurs at many points between the hypothalamic-pituitary-gonad (HPG) and hypothalamic-pituitary-thyroid (HPT) axes. Monocrotophos (MCP) pesticide could disrupt HPG and HPT axes, but its direct target within the endocrine system is still unclear. In the present study, hormone concentrations and transcriptional profiles of HPG and HPT genes were examined in male goldfish (Carassius auratus) exposed to 0, 4, 40, and 400 µg/L MCP for 2, 4, 8, and 12 d. In vivo data were analyzed by multiple linear regression and correlation analysis, quantitatively indicating that MCP-induced plasma 17ß-estradiol (E2) levels were most associated with alteration of cyp19a transcription, which was also a potential point indirectly modulated by the MCP-altered thyroid hormones (THs) status; disturbance of THs pathways was most related with effect of MCP on regulation of the hypothalamic-pituitary hormones involved in the thyroid system, and the increased E2 levels might enhance the impact of MCP on HPT axis by modulating hepatic deiodinase expression. Our finding, based on these correlational data, gave a whole view of the regulations, especially on the cross-talk between sex hormone and thyroid hormone pathways upon exposure to chemicals with unknown direct target in vivo, and cautions should be exercised when developing adverse outcome pathway networks for reproductive and thyroidal endocrine disruption.

Insights on the age dependent neurodegeneration induced by Monocrotophos, (an organophosphorous insecticide) in Caenorhabditis elegans fed high glucose: Evidence in wild and transgenic strains.

The higher susceptibility of high glucose fed C. elegans to Monocrotophos (MCP, an organophosphorus insecticide) - induced dopaminergic (DA) neuronal degeneration was recently demonstrated. Employing this acute exposure model, the impact of MCP on DA degeneration among worms of two age groups (8 and 13 d old) fed control (CO) and high glucose (GF) diet with specific focus on phenotypic alterations, oxidative impairments and associated molecular perturbations employing both wild (N2) and transgenic strains(BZ555 and NL5901) was investigated. In general, 13 d worms exhibited higher susceptibility to MCP intoxication compared to 8 d old worms. Further, MCP-exposure caused an enhanced degree of DA degeneration among glucose fed (GF) worms as evidenced by lower chemotaxis index, reduced long-term memory and increased nonanone repulsion. Biochemical analysis of 13 d GF worms also revealed a significant increase in ROS, protein carbonyls and reduced ADP/ATP ratio. Interestingly, marked increase in degeneration of dopaminergic neurons and increased in α-synuclein content was evident among 13 d GF worms exposed to MCP. Significant alterations in the mRNA expression levels of daf-2, age-1, sir 2.1 and aak-2 among 13 d GF worms was evident. Collectively these findings suggest that high intake of glucose diet aggravates MCP associated dopaminergic neuronal degeneration and the impact of increasing age under such a condition. Moreover it provides an experimental paradigm to explore the molecular targets and mechanism/s underlying the possible relationship between insecticide exposure-associated dopaminergic degeneration in humans under hyperglycemic conditions.

Secretome of Differentiated PC12 Cells Restores the Monocrotophos-Induced Damages in Human Mesenchymal Stem Cells and SHSY-5Y Cells: Role of Autophagy and Mitochondrial Dynamics.

A perturbed cellular homeostasis is a key factor associated with xenobiotic exposure resulting in various ailments. The local cellular microenvironment enriched with secretory components aids in cell-cell communication that restores this homeostasis. Deciphering the underlying mechanism behind this restorative potential of secretome could serve as a possible solution to many health hazards. We, therefore, explored the protective efficacy of the secretome of differentiated PC12 cells with emphasis on induction of autophagy and mitochondrial biogenesis. Monocrotophos (MCP), a widely used neurotoxic organophosphate, was used as the test compound at sublethal concentration. The conditioned medium (CM) of differentiated PC12 cells comprising of their secretome restored the cell viability, oxidative stress and apoptotic cell death in MCP-challenged human mesenchymal stem cells and SHSY-5Y, a human neuroblastoma cell line. Delving further to identify the underlying mechanism of this restorative effect we observed a marked increase in the expression of autophagy markers LC3, Beclin-1, Atg5 and Atg7. Exposure to autophagy inhibitor, 3-methyladenine, led to a reduced expression of these markers with a concomitant increase in the expression of pro-apoptotic caspase-3. Besides that, the increased mitochondrial fission in MCP-exposed cells was balanced with increased fusion in the presence of CM facilitated by AMPK/SIRT1/PGC-1α signaling cascade. Mitochondrial dysfunctions are strongly associated with autophagy activation and as per our findings, cellular secretome too induces autophagy. Therefore, connecting these three potential apices can be a major breakthrough in repair and rescue of xenobiotic-damaged tissues and cells.