Studies on the toxic effects of agrochemical pesticide (Monocrotophos) on physiological and reproductive behavior of indigenous and exotic earthworm species.

Earthworms are an ideal biological model in toxicity assays and environmental monitoring studies. In the present study, the reproductive toxicity and histopathological effects of Monocrotophos pesticide on an exotic epigeic Eudrilus eugeniae and an indigenous epigeic Perionyx barotensis earthworm were studied. Earthworm species were exposed to different concentrations of pesticide like 450 ppm, 500 ppm, and 650 ppm for 45 days and the mortality rate and reproductive activity was recorded every 15 days of exposure. There was an increase in mortality and abnormal sperm (asthenospermia, necrospermia, and oligospermia) and defective cocoons in earthworms with increasing concentrations of the pesticide. Histopathological changes like rupture of chloragogenous tissue, longitudinal muscle, fused and extra-villous growth and necrotic cell rupture in earthworm's body wall (epidermis, circular and longitudinal muscles) were observed. Fluorescent probes have detected cell death in pesticide-treated earthworms when compared to the control group after 45 days. The present findings show that Monocrotophos pesticide on exposure to epigeic earthworm species causes significant reproductive toxicity and histopathological abnormalities and these changes could be used as a tool in environmental risk assessment of pesticides.Abbreviations: DDT: Dichlorodiphenyltrichloroethane; MCP: Monocrotophos; EPA: Environment Protection Act; SL: Soluble Liquid; C: N (Carbon: Nitrogen); C: P (Carbon: Phosphorus); LC: Lethal Concentration; PBS: Phosphate Buffer Solution; WHO: World Health Organization; H&E: Hematoxylin and Eosin; SV: seminal vesicles; O: ovary; GP: genital papillae; Ch: chloragogenous tissue; EL: epithelial layer; CM: circular muscle; LM: longitudinal muscle; CD: cell debris.

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.

Pkb/Akt1 mediates Wnt/GSK3ß/ß-catenin signaling-induced apoptosis in human cord blood stem cells exposed to organophosphate pesticide monocrotophos.

Inhibition mechanisms of protein kinase B (Pkb)/Akt and its consequences on related cell signaling were investigated in human umbilical cord blood stem cells (hUCBSCs) exposed to monocrotophos (MCP, an organophosphate pesticide). In silico data reveal that MCP interacts with kinase and c-terminal regulatory domains of Akt1, resulting into a total docking score of 5.2748 and also forms H-bond between its N-H and Thr-291 residue of Akt1, in addition to possessing several hydrophobic interactions. The main cause of Akt inhibition is considered to be the strong hydrogen bond between N-H and Thr-291, and hydrophobic interactions at Glu-234, and Asp-292 in the vicinity, which is usually occupied by the ribose of ATP, and interaction with residue Phe-161, thus leading to a significant conformational change in that particular portion of the protein. In silico data on Akt inhibition were confirmed by examining the downregulation of phosphorylated (Thr308/Ser493) Akt1 in MCP-exposed hUCBSCs. MCP-mediated altered levels of pAkt downstream targets viz., downregulated pGSK3ß (Ser9), unchanged GSK3αß, and upregulated levels of Bad, P(53), and caspase-9 further confirm the inhibition of pAkt. The cellular fate of such pAkt inhibition was confirmed by increased terminal deoxynucleotide transferase dUTP nick-end labeling positive cells, reduced mitochondrial membrane potential, and the activation of various MAPKs, proapoptotic markers-Bax, and caspases-9/3. Our data demonstrate that Akt1 plays a key role in MCP-induced apoptosis in hUCBSCs. We also identified that such cellular responses of human cord blood stem cells against MCP were due to strong binding and inhibition of kinase and AGC-Kinase-C terminal regulatory domains of Akt1.

Three-dimensional study on the effect of organophosphate pesticide 'monocrotophos' on lens of fish and its recovery.

The present studies are based on the feedback provided by fish farmers practicing composite fish culture of carps. According to them, fish habitats are affected by pesticides draining from agricultural fields into their catchments, especially during the rainy season. The lenses of most of the cultured fish became opaque, resulting in poor overall growth. In the literature, there was mounting evidence of pesticide toxicity involving multiple tissues. However, the fish visual system has never been investigated particularly from the toxicological perspective. In this regard, we carried out comparative toxicological studies on the lens of Cyprinus carpio communis using three different sublethal concentrations (0.038, 0.062 and 0.126 p.p.m.) of monocrotophos along with untreated controls for 30 days. Lenses from all the groups were extracted and preserved in gluteraldehyde and osmium tetraoxide and dehydrated in increasing grades of acetone. After dehydration, tissues were conducted with gold to observe under SEM. The fish exposed to monocrotophos developed cataract. Furthermore, when fish from the monocrotophos-treated tanks were transferred to normal environmental conditions for the next 60 days, progressive lens degeneration was noted. To conclude, monocrotophos induces irreversible cataractous changes in the lens of C. carpio communis. The fish visual system has many similarities to mammals and may serve as a good model for comparative toxicologic and ophthalmologic studies.

Long-term effects of a novel phosphorothionate (RPR-II) on detoxifying enzymes in brain, lung, and kidney rats.

The effects of a phosphorothionate, 2-butenoic acid-3-(diethoxyphosphinothioyl) methyl ester (RPR-II), on the activities of glutathione S-transferase (GST) and UDP-glucuronyltransferase (UDPGT) and the level of glutathione (GSH) were evaluated in rats after administration of RPR-II at 0.014 (low), 0.028 (medium), and 0.042 (high) mgkg(-1)day(-1) for 90 days and also at 28 days (withdrawal) after stopping treatment. Brain GST activity and GSH level decreased significantly at the high dose on the 45th and 90th days of treatment. Dose- and time-dependent decreases in GST activity and GSH was level were observed in lung at medium and high doses and in kidneys at all three doses on both the 45th and 90th days. UDPGT activity increased significantly in kidneys at the medium and high doses at 45 and 90 days. Brain and lung did not display any significant variations in UDPGT activity when compared with the control. Interestingly, the withdrawal study revealed that the effect was reversible within 28 days of cessation of treatment, when enzyme activity reverted to levels close to those of controls. The study revealed that RPR-II affected the GSH- and GST-dependent detoxification system of the treated tissues of rat and its potential to modulate the enzymes is in the order kidneys>lung>>brain. The present subacute study suggests that RPR-II may bring about physiological upsets by altering GSH- and GST-dependent events in different tissues of exposed organisms.

Subarachnoid hemorrhage and rhabdomyolysis induced acute renal failure complicating organophosphate intoxication.

Organophosphate is extremely uncommon cause of rhabdomyolysis. This article describe two cases with rhabdomyolysis induced acute renal failure complicating by monocrotophos, an organophosphate compound. First patient had rhabdomyolysis induced acute renal failure and subarachnoid hemorrhage. This is the first reported case of subarachnoid hemorrhage, which may be related with organophosphate intoxication in literature. Second patient described here had rhabdomyolysis induced acute renal failure after organophosphate overdose.

Gill lesions in the perch, Anabas testudineus, exposed to monocrotophos.

Histopathological effects of sublethal doses of monocrotophos on the gills have been studied by exposing the fish for a period ranging from ten to twenty days. The extent of damage to gills was dependent on the dose and duration of exposure. Histopathological changes in the gills observed were characterized primarily by hemorrhage in the primary and secondary gill lemellae. Degeneration and necrosis of epithelial cells were very prominent. Distortion of the secondary lamellae was very prominent, beginning with disruption of epithelial cells from pillar cells.

Toxicology of monocrotophos.

Monocrotophos is a water-soluble organophosphate insecticide with high oral and moderate dermal toxicity. The toxicologically relevant mode of action is the inhibition of ChE activities. The toxicity of organophosphate metabolites of monocrotophos is comparable with the parent compound. Glycol conjugation in plant metabolism decreased the acute toxicity significantly. Dephosphorylated metabolites showed no demonstrable acute toxicity. Repeated exposure to the compound leads to initial cumulation of the single-dose effects. At moderate dose levels, the adverse effects are counteracted by an increase of tolerance through adaptation. A study in humans demonstrated no relevant ChE depression over a 30-d period at daily dose levels of up to 0.006 mg/kg. Lifetime chronic feeding studies in rodents again indicated ChE inhibition as the only specific effect. Body weight reduction was limited to high doses. No gross or microscopic specific lesions were demonstrable; especially, there was no evidence of oncogenic effects. Genotoxicity was evident in vitro, whereas comprehensive assessment of the in vivo tests indicates no toxicologically relevant mutagenic potential in mammals. This conclusion is supported by the absence of oncogenic effects in chronic feeding trials. Findings in reproduction studies were limited to secondary fetal reactions that were triggered by maternal toxicity. Acute and repeated administration studies in hens revealed no delayed (degenerative) neurotoxic potential. Monocrotophos showed no significant potentiation with 24 other ChE inhibitors. Poisoning signs after heavy doses were controlled by therapeutic doses of atropine, preferably in combination with an oxime.