Monocrotophos Exposure Research Articles

Exposure to monocrotophos pesticide causes disruption of the hypothalamic–pituitary–thyroid axis in adult male goldfish (Carassius auratus)

The thyroid hormones (THs) 3,3′,5-triiodo-l-thyronine (T3) and l-thyroxine (T4) exert a wide range of biological effects on physiological processes of fish. To elucidate the thyroid disruption effects of monocrotophos (MCP), an organophosphate pesticide, on male goldfish (Carassius auratus), thyroid follicle histology, plasma total T3 (TT3), total T4 (TT4), free T3 (FT3) and free T4 levels, and the mRNA expression of indices involved in the hypothalamic–pituitary–thyroid axis (HPT axis) were examined following 21-day exposure to 0.01, 0.10 and 1.00mg/L of a 40% MCP-based pesticide. The results showed that MCP exposure induced the hyperplasia and hypertrophy of thyroid follicular epithelium and led to decreased plasma TT3 levels and TT3-to-TT4 ratios, without effect on plasma TT4 levels. Profiles of the changes in the relative abundance of deiodinase (D1, D2 and D3) transcripts were observed in the liver, brain and kidneys, during MCP exposure. An increase in the metabolism of T3, expressed as highly elevated hepatic d1 and d3 mRNA levels, might be associated with the reduction in plasma TT3 levels in both the 0.01 and 0.10mg/L groups, while in the 1.00mg/L MCP group, inhibited hepatic d2 transcripts might have also resulted in decreased TT3 levels by preventing the activation of T4 to T3. As a compensatory response to decreased T3 levels, pituitary thyroid-stimulating hormone β subunit mRNA transcription was up-regulated by the MCP pesticide. Decreases in plasma FT3 levels were also correlated with the modulation of hepatic transthyretin mRNA expression. Overall, the MCP pesticide exhibited thyroid-disrupting effects via interference with the HPT axis at multiple potential sites, resulting in disturbance of TH homeostasis.

Monocrotophos pesticide modulates the expression of sexual differentiation genes and causes phenotypic feminization in zebrafish (Danio rerio)

Monocrotophos (MCP) is an organophosphorus pesticide moderately toxic to fish, and it has significant estrogenic properties in vivo. In this study, zebrafish (Danio rerio) were exposed to 0.001, 0.010, and 0.100mg/L 40% MCP pesticide in a semi-static manner from fertilization to 40days post-hatching. Histological analyses were performed to determine whether sex differentiation in zebrafish was affected by MCP, and the mRNA expression levels of genes involved in sexual differentiation were quantified by real-time PCR to clarify the possible mechanism(s) of action. The results revealed a prominent increase in the proportion of females (71%) in the 0.100mg/L MCP pesticide treatment as well as the presence of one intersex individual in each of the groups exposed to 0.001 and 0.100mg/L MCP. MCP exposure stimulated forkhead transcription factor gene L2 (foxl2) expression and suppressed doublesex/mab-3 related transcription factor 1 (dmrt1) expression, indirectly leading to elevated gonadal aromatase (cyp19a1a) gene expression, which should promote phenotypic feminization. In addition, MCP treatment increased the transcription of brain aromatase (cyp19a1b), resulting in an indirect impact on sexual differentiation. The results from this investigation can be used for risk and hazard assessment of MCP pesticide.

Effects of monocrotophos on the reproductive axis in the female goldfish ( Carassius auratus)

Monocrotophos (MCP) is a highly toxic organophosphorus pesticide. To elucidate the influence of MCP on female fish reproduction, plasma 17 β-estradiol, testosterone and gonadotropin levels and aromatase and gonadotropin β subunit gene expression levels were examined in female goldfish ( Carassius auratus) following a 21-day exposure to 0.01, 0.10 and 1.00 mg L− 1 40% MCP-based pesticide in a semi-static exposure system. The results indicated that MCP induced increases in plasma 17 β-estradiol levels and the 17 β-estradiol/testosterone ratio via interference with the reproductive axis at multiple potential sites through two mechanisms: (a) MCP exposure enhanced the mRNA expression of gonadal aromatase, the enzyme that converts androgens into estrogens, consequently reducing plasma testosterone levels and increasing plasma concentrations of 17 β-estradiol; and (b) MCP treatment increased follicle-stimulating hormone β subunit mRNA expression and secretion and decreased luteinizing hormone β subunit mRNA expression and secretion, leading to the disruption of reproductive endocrine control and androgen and estrogen balance. This study provided convincing evidence for reproductive toxicology of MCP by disrupting of the HPG axis at multiple sites in female goldfish.

Effects of monocrotophos on the reproductive axis in the male goldfish ( Carassius auratus): Potential mechanisms underlying vitellogenin induction

Monocrotophos (MCP) is a highly toxic organophosphorus pesticide that has been banned in many countries. Both vitellogenin mRNA expression and secretion were significantly induced in male goldfish by exposure to an MCP-based pesticide, suggesting that MCP has significant estrogenic properties. To elucidate the mechanisms of action of MCP on vitellogenin induction, we used radioimmunoassay to examine the effect of MCP treatment on plasma 17β-estradiol and testosterone levels in male goldfish ( Carassius auratus). We also investigated the potential impacts of MCP treatment on aromatase expression, on the synthesis and secretion of pituitary gonadotropins and on the regulation of hypothalamic gonadotropin-releasing hormones by real-time PCR and radioimmunoassay. Experiments were carried out during the period of gonadal late recrudescence following a 21-day exposure to 0.01, 0.10 and 1.00 mg L −1 of a pesticide containing 40% MCP in a semi-static exposure system. The results indicated that males in each MCP treatment group had much higher plasma levels of 17β-estradiol, suggesting that the induction of VTG production by MCP was indirectly caused by elevated levels of endogenous 17β-estradiol. MCP-induced plasma 17β-estradiol levels via interference with the reproductive axis at multiple potential sites in male goldfish: (a) MCP exposure enhanced the mRNA expression of gonadal aromatase, the enzyme that converts androgens into estrogens, consequently reducing plasma levels of testosterone and increasing plasma concentrations of 17β-estradiol; (b) MCP treatment increased follicle-stimulating hormone β subunit mRNA expression and protein secretion and decreased luteinizing hormone β subunit mRNA expression and protein secretion, thus interfering with gonadotropin synthesis and secretion at the pituitary level and leading to the disruption of reproductive endocrine control and androgen and estrogen balance.

Effects of combined exposure to dichlorvos and monocrotophos on blood and brain biochemical variables in rats

Dichlorvos (DDVP) and monocrotophos (MC) are systemic insecticides and known to produce cholinergic and non-cholinergic effects. Individual toxic effects of these chemicals are known but their combined effects have not been studied. We studied the effect of concomitant exposure to DDVP and MC on selected biochemical variables suggestive of liver damage, changes in whole brain biogenic amines levels, acetylcholinesterase (AchE) and monoamine oxidase (MAO) activities in rats. Female rats were exposed to DDVP (2.5 mg/kg subcutaneously) and MC (1.8 mg/kg oral) either individually or in combination for 4 weeks. We observed significant decrease in more pronounced depletion in norepinephrine (NE) and dopamine (DA) levels during co-exposure to DDVP and MC. Brain AChE activity increased and activity of MAO showed significant depletion on co-exposure to DDVP and MC. Brain glutathione (GSH) and oxidized glutathione (GSSG) ratio decreased significantly during exposure to DDVP or MC while co-exposure to these toxicants led to a more pronounced depletion of GSH: GSSG ratio. Serum aspartate amino transferase (AST) and alkaline phosphatase (ALP) activities increased significantly on exposure to MC suggesting liver injury, while DDVP alone had no effect on these variables. There were no effects of DDVP and MC exposure on haematological biochemical variables except for depletion in serum glucose level after MC exposure which was more pronounced DDVP + MC during co-exposure. It can be concluded that only moderate synergistic effects occur between MC and DDVP during co-exposure. A more detailed study with variable doses, prolonged exposure and alterations in different brain regions is recommended.

Mitochondrial ATP synthase inhibition and nitric oxide are involved in muscle weakness that occurs in acute exposure of rats to monocrotophos

Organophosphate poisoning in the context of self-harm is a common medical emergency in Asia. Prolonged muscle weakness is an important but poorly understood cause of morbidity and mortality of the poisoning. This study examined mitochondrial function and its modulation by nitric oxide in muscle weakness of rats exposed to an acute, oral (0.8LD50) dose of monocrotophos. Muscle mitochondrial ATP synthase activity was inhibited in the rat in acute exposure to monocrotophos while respiration per se was not affected. This was accompanied by decreased mitochondrial uptake of calcium and increased levels of nitric oxide. Reactive cysteine groups of ATP synthase subunits were reduced in number, which may contribute to decreased enzyme activity. The decrease in ATP synthase activity and reactive cysteine groups of ATP synthase subunits was prevented by treatment of animals with the nitric oxide synthase inhibitor, L-NG Nitroarginine methyl ester, at 12 mg/kg body weight for 9 days in drinking water, prior to monocrotophos exposure. This indicated a role for nitric oxide in the process. The alterations in mitochondrial calcium uptake may influence cytosolic calcium levels and contribute to muscle weakness of acute organophosphate exposure.

In Vivo and In Vitro Inhibitions of Red Drum (Sciaenops ocellatus) Brain Acetylcholinesterase and Liver Carboxylesterase by Monocrotophos at Sublethal Concentrations

The toxic effects of monocrotophos at sublethal concentrations on red drum (Sciaenops ocellatus) brain acetylcholinesterase (AChE, EC 3.1.1.7) and liver carboxylesterase (CaE, EC 3.1.1.1) were examined. After monocrotophos exposure for 4 days at 0.25, 0.5, 1 and 2 mgL-1 respectively, the AChE activity goes down progressively with the increaseof monocrotophos concentration, and CaE activity reaches the lowest rapidly at the lowest monocrotophos concentration and keeps almost the lowest with the increase of monocrotophos concentration. In time-effect experiments, after exposure to 0.5 mg L-1 monocrotophos for 1, 2, 4 and 7 days, the activities of two enzymes change in similar trends as found in concentration-effect experiment. The in vivo inhibitions of brain AChE by monocrotophos depend better on concentration and time than CaE. The inhibition of brain AChE by monocrotophos are weaker significantly than that of liver CaE, revealing that CaE may protect AChE in vivo. In addition, half inhibition concentration(IC50) of CaE is significantly lower than AChE(7.2 × 10-4 mmol L-1 vs 0.21 mmol L-1), explaining the protection role of CaE on AChE.

Biochemical changes in the liver of fish, Tilapia mossambica (Peters), during continuous exposure to monocrotophos

The purpose of the present investigation was to determine the effect of continuous exposure to the organophosphate monocrotophos at 2.5 ppm for over a period of 2 through 45 days on protein, RNA, and DNA contents and on 5′-nucleotidase activity in the liver of Tilapia mossambica. Protein content was decreased by 45% after 5 days, returned to control levels at 10–30 days, and again decreased by 45 days. DNA content was decreased by 2 days, returned to control values by 5 days, and remained constant throughout the exposure. In contrast, RNA content was significantly lower starting from 2 through 45 days of exposure. 5′-Nucleotidase activity showed a transient increase at 5 and 30 days of monocrotophos exposure. These results indicate that monocrotophos altered the protein, DNA, and RNA contents and the 5′-nucleotidase activity levels as early as 2 and 5 days. However, these changes were reversed by 10 days and after a short period of recovery, the alterations reappeared. This supports our earlier histological observations of hepatic pathology during monocrotophos exposure.