RESUMO
Morin is a flavonoid which is present in many plants. Endosulfan and 7,12-dimethylbenz[a]anthracene (DMBA) are toxic chemicals that humans are exposed to in their daily lives. In this study, the protective role of morin was investigated in endosulfan and DMBA treated rats. Eight groups, each comprising seven 2.5-month-old adult male Wistar rats (weighing 170-255 g), were used. Endosulfan, morin, and DMBA were administered individually or in combinations, at 5 mg/kg body weight (bw) (three times/week), 25 mg/kg bw (three times/week), and 30 mg/kg bw (once/week for three weeks) via oral gavage, respectively. On day 54 of the administration period, the rats were killed. DMBA + endosulfan co-administration significantly increased CYP1A1-, CYP1A2-, CYP2E-, and GST-associated activities in the rats compared to the control. DMBA + endosulfan + morin significantly increased CYP1A1, CYP1A2, CYP3A, and GST associated activities in the rats relative to the control. Histopathological studies were performed to investigate protective effects of morin on liver damage. The results indicated that DMBA + endosulfan treatment induced liver damage, and morin reduced this damage. These findings suggest that CYP1A, CYP3A, and GST enzyme activities participate in the protective mechanism of morin against endosulfan and DMBA induced toxicity.
Assuntos
9,10-Dimetil-1,2-benzantraceno/toxicidade , Endossulfano/toxicidade , Flavonoides/farmacologia , Fígado/efeitos dos fármacos , 9,10-Dimetil-1,2-benzantraceno/administração & dosagem , Animais , Sistema Enzimático do Citocromo P-450/metabolismo , Endossulfano/administração & dosagem , Flavonoides/administração & dosagem , Glutationa Transferase/metabolismo , Fígado/enzimologia , Fígado/patologia , Masculino , Ratos , Ratos Wistar , Xenobióticos/metabolismoRESUMO
Endosulfan is a DDT-era organochlorine pesticide. Due to past and current environmental contamination, investigation of endosulfan exposure is of current importance. Acute high dose exposure precipitates neural/endocrine system damage, but the effects on the immune system and of lower doses are not well-characterized. Two relatively low concentrations of endosulfan (i.e. 0.1 and 17 µM ENDO) were investigated in an in vitro study using human peripheral blood mononuclear cells (PBMC) to understand effects of relatively low doses (0.1-25.0 µM [≈0.04-10 ppm/40-10,000 ppb]) of ENDO upon normal human T- and B-lymphocytes and NK cells. The study here found that 17 µM ENDO inhibited phytohemagglutinin-M (PHA)-induced human PBMC proliferation. It was also seen that senescence and apoptosis among non-stimulated cells was increased, specifically within CD8 and NK populations, and that CD4:CD8 ratios also were increased. Treatment of non-stimulated PBMC with ENDO led to overall increases in production of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-2, -4, and -6, and decreased production of anti-inflammatory IL-10, suggesting an immunosenescence secretory phenotype. Interestingly, when the cells were pre-stimulated with mitogen (PHA), ENDO became inhibitory against the mitogen-induced proliferation and cytokine formation - with the exception of that of TNFα and IL-6, suggesting differential effects of ENDO on activated cells. Thus, at the organismal level, ENDO might also display differential effects during states of autoimmune disease or chronic viral infection in the exposed host.
Assuntos
Proliferação de Células/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Endossulfano/toxicidade , Inseticidas/toxicidade , Linfócitos T Citotóxicos/efeitos dos fármacos , Adulto , Linfócitos B/efeitos dos fármacos , Linfócitos B/fisiologia , Células Cultivadas , Senescência Celular/imunologia , Citocinas/imunologia , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Endossulfano/administração & dosagem , Feminino , Voluntários Saudáveis , Humanos , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Inseticidas/administração & dosagem , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/fisiologia , Masculino , Cultura Primária de Células , Linfócitos T Citotóxicos/fisiologia , Adulto JovemRESUMO
Proper myometrial adaptation during gestation is crucial for embryo implantation, pregnancy maintenance and parturition. Previously, we reported that neonatal exposure to endosulfan alters uterine development and induces implantation failures. The present work investigates the effects of endosulfan exposure on myometrial differentiation at the pre-implantation period, and myometrial activation during labor. Newborn female rats were s.c. injected with corn oil (vehicle) or 600⯵g/kg/day of endosulfan (Endo600) on postnatal days (PND) 1, 3, 5 and 7. On PND90, the rats were mated to evaluate: i) the myometrial differentiation on gestational day 5 (GD5, pre-implantation period), by assessment myometrial histomorphology, smooth muscle cells (SMCs) proliferation, and expression of proteins involved in myometrial adaptation for embryo implantation (steroid receptors, Wnt7a and Hoxa10); ii) the timing of parturition and myometrial activation during labor by determining the uterine expression of contraction-associated genes (oxytocin receptor, OTXR; prostaglandin F2α receptor, PTGFR and connexin-43, Cx-43). Endosulfan decreased the thickness of both myometrial layers, with a concomitant decrease in the collagen remodeling. Blood vessels relative area in the interstitial connective tissue between muscle layers was also decreased. Endo600 group showed lower myometrial proliferation in association with a downregulation of Wnt7a and Hoxa10. Although in all females labor occurred on GD23, the exposure to endosulfan altered the timing of parturition, by inducing advancement in the initiation of labor. This alteration was associated with an increased uterine expression of OTXR, PTGFR and Cx-43. In conclusion, neonatal exposure to endosulfan produced long-term effects affecting myometrial adaptation during early pregnancy and labor. These alterations could be associated with the aberrant effects of endosulfan on the implantation process and the timing of parturition.
Assuntos
Adaptação Fisiológica/efeitos dos fármacos , Endossulfano/administração & dosagem , Inseticidas/administração & dosagem , Trabalho de Parto/efeitos dos fármacos , Miométrio/efeitos dos fármacos , Contração Uterina/efeitos dos fármacos , Útero/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Diferenciação Celular , Feminino , Trabalho de Parto/metabolismo , Miométrio/crescimento & desenvolvimento , Miométrio/metabolismo , Gravidez , Ratos , Ratos Wistar , Contração Uterina/metabolismo , Útero/crescimento & desenvolvimento , Útero/metabolismoRESUMO
This study evaluated the in vitro effect of three concentrations of atrazine, chlorpyrifos and endosulfan on the growth parameters of four non-toxigenic Aspergillus section Flavi strains. The ability of the strains to remove these pesticides in a synthetic medium was also determined. Growth parameters were measured on soil extract solid medium supplied with 5, 10 and 20mg/l of each pesticide, and conditioned to -0.70, -2.78, -7.06 and -10.0 water potential (MPa). Removal assays were performed in Czapek Doc medium (CZD) supplied with 20mg/l of each pesticide under optimal environmental conditions (-2.78 of MPa and 25°C). The residual levels of each pesticide were detected by the reversed-phase HPLC/fluorescence detection system. The lag phases of the strains significantly decreased in the presence of the pesticides with respect to the control media. This result indicates a fast adaptation to the conditions assayed. Similarly, the mycelial growth rates in the different treatments increased depending on pesticide concentrations. Aspergillus oryzae AM 1 and AM 2 strains showed high percentages of atrazine degradation (above 90%), followed by endosulfan (56 and 76%) and chlorpyrifos (50 and 73%) after 30 days of incubation. A significant (p<0.001) correlation (r=0.974) between removal percentages and growth rate was found. This study shows that non-toxigenic Aspergillus section Flavi strains from agricultural soils are able to effectively grow in the presence of high concentrations of atrazine, chlorpyrifos and endosulfan under a wide range of MPa conditions. Moreover, these strains have the ability to remove high levels of these pesticides in vitro in a short time.
Assuntos
Aspergillus flavus/crescimento & desenvolvimento , Aspergillus flavus/metabolismo , Atrazina/administração & dosagem , Atrazina/metabolismo , Clorpirifos/administração & dosagem , Clorpirifos/metabolismo , Endossulfano/administração & dosagem , Endossulfano/metabolismo , Herbicidas/administração & dosagem , Inseticidas/administração & dosagem , Aspergillus flavus/efeitos dos fármacos , Atrazina/farmacologia , Clorpirifos/farmacologia , Relação Dose-Resposta a Droga , Endossulfano/farmacologia , Herbicidas/farmacologia , Inseticidas/farmacologiaRESUMO
Low levels of endosulfan are known to stimulate mast cells to release allergic mediators, while imidacloprid can inhibit IgE-mediated mast cell degranulation. However, little information about the effects of both pesticides together on mast cell degranulation is available. To measure the effects, IgE-activated mouse bone marrow-derived mast cells (BMMCs) were treated with imidacloprid and endosulfan, individually, and simultaneously at equi-molar concentrations in tenfold steps ranging from 10-4 to 10-11â¯M, followed by measuring several allergy-related parameters expressed in BMMCs: the mediator production and influx of Ca2+, the phosphorylation content of NF-κB in the FcεRI signaling pathway. Then, the effects of the mixtures on IgE-induced passive systemic anaphylaxis (PSA) of BALB/c was detectded. This study clearly showed that the application of equi-molar mixtures of both pesticides with 10-4-10-5â¯M significantly inhibited the IgE-mediated mouse bone marrow-derived mast cells degranulation in vitro and 10-4â¯M of them decreased IgE-mediated PSA in vivo, as the application of imidacloprid at the same concentration alone did. Morever endosulfan alone had no remarkable stimulatory effects on any of the factors measured. In conclusion, simultaneous application of equi-molar concentrations of both pesticides generally showed highly similar responses compared to the responses to imidacloprid alone, suggesting that the effects of the mixture could be solely attributed to the effects of imidacloprid.
Assuntos
Anafilaxia/induzido quimicamente , Células da Medula Óssea/efeitos dos fármacos , Degranulação Celular/efeitos dos fármacos , Endossulfano/farmacologia , Imunoglobulina E/administração & dosagem , Mastócitos/efeitos dos fármacos , Neonicotinoides/farmacologia , Nitrocompostos/farmacologia , Praguicidas/farmacologia , Anafilaxia/metabolismo , Animais , Células da Medula Óssea/metabolismo , Cálcio/metabolismo , Endossulfano/administração & dosagem , Transporte de Íons , Mastócitos/metabolismo , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Neonicotinoides/administração & dosagem , Nitrocompostos/administração & dosagem , Fosforilação , Receptores de IgE/metabolismo , Transdução de SinaisRESUMO
Agricultural activities associated mainly with soybean crops affect the natural environment and wildlife by habitat destruction and the extensive use of agrochemicals. The aim of this study was to evaluate immunotoxic effects of the insecticides cypermethrin (CYP) and endosulfan (END) in Caiman latirostris analyzing total blood cell count (TWBC) and differential white blood cell count (DWBC) after in ovo and in vivo exposure. Eggs (in ovo) and hatchlings (in vivo) from nests harvested in natural habitats were artificially incubated and reared under controlled conditions in the Proyecto Yacaré (Gob.Santa Fe/MUPCN) facilities. Exposure of embryos was performed by topication on the eggshell during the first stage of development. The treatments were distilled water (negative control; NC), ethanol (vehicle control; VC), four groups treated with different concentrations of CYP and four groups with END. In vivo exposure was performed by immersion; treatments were NC, VC, two groups exposed to CYP and two to END. After embryonic exposure to the insecticides, no differences were found in TWBC or DWBC among the neonates exposed to pesticides versus controls. In the in vivo scenario, similar results were obtained for TWBC, but DWBC data showed differences between NC hatchlings and CYP-1 hosts for heterophil, lymphocyte and monocyte levels, and between NC and END-1 hosts for lymphocyte and monocyte levels. Research on the effects of pesticide exposure on this species is of special interest not only to assess the impact on caiman populations, but also to further characterize the species as a potential sentinel of ecosystem health.
Assuntos
Jacarés e Crocodilos/imunologia , Endossulfano/administração & dosagem , Inseticidas/administração & dosagem , Leucócitos/imunologia , Óvulo/imunologia , Piretrinas/administração & dosagem , Animais , Animais Recém-Nascidos , Endossulfano/efeitos adversos , Exposição Ambiental/efeitos adversos , Inseticidas/efeitos adversos , Contagem de Leucócitos , Piretrinas/efeitos adversosRESUMO
Endosulfan (ENDO) is a widely used organochlorine (OC) pesticide and persistent organo-pollutant. Epidemiological studies have shown that high levels of OC exposure were related to colorectal cancer (CRC) incidence. The objectives of the present study were to evaluate histological changes in the colon, as well as in in situ expression of ß-catenin and P-selectin, and serum levels of select pro-inflammatory cytokines in mice administered ENDO; there is a relationship between increased serum IL-6 and P-selectin levels in CRC patients and aberrant ß-catenin signaling is important in initiation/maintenance of most CRCs. Mice were exposed to ENDO (at dose < LD50) orally once a week for up to 24 weeks, and monitored (inclusive) for a total of 42 weeks. The experiment was comprised of three groups, one that did not receive ENDO (olive oil vehicle), one administered 2 mg ENDO/kg/week and a positive control (for induction of CRC) given a weekly 20 mg 1,2-dimethylhydrazine (DMH)/kg injection. The results indicated that oral administration of ENDO provoked moderate inflammation starting at six weeks, and severe colonic inflammation with an appearance of dysplastic formations (aberrant crypts) in mice treated with ENDO (or DMH) for 12 weeks or longer. Serum IL-6 levels significantly increased starting at six weeks and rose to a peak of 15-fold higher than in controls at 42 weeks; TNFα levels likewise significantly increased, with a later peak (≈four-fold higher than controls) at 30-42 weeks. Immunohistochemical analysis of the colon also showed that expression of ß-catenin and P-selectin increased with length of exposure to ENDO. Taken together, the results indicate that continued repeated oral exposure to ENDO induces increased expression of ß-catenin and P-selectin, inflammation in the colon, and, ultimately, local tissue dysplasia.
Assuntos
Colite/imunologia , Colo/imunologia , Neoplasias Colorretais/epidemiologia , Endossulfano/administração & dosagem , Inflamação/imunologia , 1,2-Dimetilidrazina/administração & dosagem , Administração Oral , Animais , Neoplasias Colorretais/imunologia , Endossulfano/imunologia , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Selectina-P/metabolismo , Praguicidas/imunologia , Fator de Necrose Tumoral alfa/metabolismo , beta Catenina/genética , beta Catenina/metabolismoRESUMO
Neonatal exposure to a low dose of endosulfan may disrupt the expression of Wnt7a and ß-catenin during uterine development leading to the failure of uterine functional differentiation during implantation. New-born female Wistar rats were treated with vehicle, endosulfan (600 µg/kg/d, E600) or diethylstilbestrol (0.2 µg/kg/d, DES) on postnatal days (PNDs) 1, 3, 5 and 7. Subsequently, uterine histomorphology and the protein expression of Wnt7a and ß-catenin were evaluated on PND8, PND21 and gestational day (GD) 5 (pre-implantation period). In the E600 rats, Wnt7a and ß-catenin protein expression was increased in the epithelium on PND8, and Wnt7a expression was decreased in the endometrial glands on PND21. On GD5, the number of uterine glands was decreased in the E600-and DES-treated rats. In addition, Wnt7a expression was decreased in all uterine compartments, and ß-catenin expression was increased in the luminal and glandular epithelia of the E600-and DES-treated rats. Disruption of Wnt7a and ß-catenin uterine expression in the prepubertal and adult females altered the uterine preparation for embryo implantation, which could be associated with the subfertility triggered by endosulfan.
Assuntos
Endossulfano/efeitos adversos , Proteínas Proto-Oncogênicas/metabolismo , Útero/efeitos dos fármacos , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Animais , Animais Recém-Nascidos , Diferenciação Celular/efeitos dos fármacos , Dietilestilbestrol/toxicidade , Endossulfano/administração & dosagem , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Ratos , Ratos Wistar , Útero/crescimento & desenvolvimento , Útero/metabolismoRESUMO
Endosulfan, a chlorinated hydrocarbon insecticide/acaricide, is a member of a cyclodiene sub-group of poisons to a wide variety of insects and mites. It is also toxic to humans and animals, but there is limited knowledge about endosulfan-related splenic and overall immunotoxicity. The aim of this study was to review pathological findings of endosulfan toxicity in the spleen and to examine potential protective effects of the anti-oxidant Vitamin C (Vit C). Here, after 6-week exposures, the spleens of New Zealand White rabbits were examined grossly and histopathologically and tissue caspase-3 activity was assessed immunohistochemically. Rabbits in four groups were used: Group END were given by oral gavage a sub-lethal dose of endosulfan (1 mg/kg) in corn oil daily for 6 weeks; Group END + C received the same dose of endosulfan daily and Vit C (20 mg/kg) every other day by gavage during this period; Group Vit C received oral corn oil daily and 20 mg/kg Vit C every other day; and Group OIL received corn oil daily for 6 weeks. Analyses of the tissues collected 1 week after the final dosing revealed lymphocyte depletion and necrosis in spleens of the hosts that received the pesticide (END only and END + C); hemorrhage and slight neutrophilic infiltration was also noted. Caspase-3 immunoreactivity was marked in lymphocytes in all spleens of rabbits in both END groups. Overall, these toxicities were mitigated by Vit C co-treatment; in END + C hosts, markedly decreased depletion of lymphocytes, inflammation and caspase-3 immunoreactivity were observed. However, even with mitigation, the level of toxicity present was still greater than any seen in the spleens of hosts that received OIL or Vit C alone. These results revealed endosulfan could cause toxicity in the rabbit spleen, characterized by depletion of lymphocytes, inflammation, necrosis and hemorrhage, and that this toxicity could begin to be mitigated by Vit C co-treatment.
Assuntos
Antioxidantes/administração & dosagem , Ácido Ascórbico/administração & dosagem , Endossulfano/administração & dosagem , Hemorragia/imunologia , Inflamação/imunologia , Linfócitos/patologia , Baço/patologia , Animais , Caspase 3/metabolismo , Endossulfano/toxicidade , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Imuno-Histoquímica , Inflamação/induzido quimicamente , Inflamação/prevenção & controle , Linfócitos/efeitos dos fármacos , Necrose , Infiltração de Neutrófilos/efeitos dos fármacos , Praguicidas/toxicidade , Coelhos , Baço/efeitos dos fármacosRESUMO
The spotted murrel, Channa punctatuswere exposed to sub-lethal concentration of endosulfan (8.1 microg l(-1)) for 12, 24, 48, 72 and 96 hrto elucidate the impact of pesticide on fatty acid composition of liver and muscle. After endosulfan exposure, fish from each control and experimental tanks were randomly sampled anesthetized, sacrificed and then the liver and muscle were dissected out for lipid and fatty acid (FA) profile. Results showed that total lipid, cholesterol, and triglyceride and FA in liver and muscle, and phospholipid in liver were significantly affected due to pesticide exposure. In liver and muscle tissues, 28.09 and 32.57% reduction of the total lipid, and 42.82 and 49.75% reduction in triglyceride and FAwere observed at the end of 96 hrs of exposure. Reduction of total lipid, triglyceride and FA may be due to their mobilization for energy production to combat stress. In FA, oleic (25.46 to 22.48% in liver and 25.75 to 21.87% in muscle) and linoleic acids (8.04 to 6.83% in liver and 9.88 to 8.09%) were reduced in both the tissues at the end of 96 hr of exposure. It may be concluded that exposure of fish to sub-lethal concentration of endosulfan had influenced the lipid and fatty acid metabolism of Channa punctatus.
Assuntos
Endossulfano/toxicidade , Ácidos Graxos/metabolismo , Peixes/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Endossulfano/administração & dosagem , Fígado/metabolismo , Músculo Esquelético/metabolismo , Poluentes Químicos da Água/administração & dosagemRESUMO
We exposed African catfish Clarias gariepinus from embryo-larvae stage to adult stage (13 months old, BW) to chronic doses of Tihan 175 O-TEQ and endosulfan (Thionex) and assessed the impact of this exposure on endocrine regulation, liver status and offspring fitness. Endosulfan exposure caused a significant increase in plasma estradiol-17ß (E2) and decreased plasma testosterone (T) but not 11 ketotestosterone (11-KT). Tihan decreased significantly plasma E2 and 11-KT, but not T. Endosulfan doses altered gonad histology and induced high proportions (1830% of males) of ovotestis in males and follicular atretic oocytes in females, indicating occurrence of feminization in fish. Tihan also altered gonad histology but only one case of ovotestis was observed at the highest dose. Presence of foam cells in lobular lumen, fibrosis, necrosis, and immature cells released in lobular lumen were found in male gonads and melano-macrophage centers (MMCs), necrosis, fibrosis and vacuolation were observed in female gonads. Fish livers also suffered injuries such as MMCs, necrosis, fibrosis, vacuolation, dilatation of sinusoids, and nuclear pleomorphism. Chronic Tihan and Thionex exposures decreased fertilization rate, hatching rate, ova and larval weight, as well as larval resistance to osmotic choc. They also delayed hatching and increased abnormalities in the F1 generation, all these indicators suggesting transgenerational effects of these compounds.
Assuntos
Peixes-Gato , Endossulfano/toxicidade , Aptidão Genética/efeitos dos fármacos , Inseticidas/toxicidade , Fígado/efeitos dos fármacos , Maturidade Sexual/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Endossulfano/administração & dosagem , Monitoramento Ambiental , Feminino , Gossypium , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Masculino , Ovário/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testosterona , Poluentes Químicos da Água/toxicidadeRESUMO
We investigated whether neonatal exposure to low doses of endosulfan affects fertility and uterine functional differentiation at pre-implantation in rats. Newborn female rats received the vehicle, 0.2 µg/kg/d of diethylstilbestrol (DES), 6 µg/kg/d of endosulfan (Endo6) or 600 µg/kg/d of endosulfan (Endo600) on postnatal days (PND) 1, 3, 5, and 7. On PND90, the rats were mated to evaluate their reproductive performance on gestational day (GD) 19 and their ovarian steroid serum levels, endometrial proliferation and implantation-associated proteins on GD5. DES and endosulfan decreased the pregnancy rate and the number of implantation sites. On GD5, DES and endosulfan did not change the serum levels of 17ß-estradiol (E2) and progesterone (P); the endometrial proliferation decreased, which was associated with silencing of Hoxa10 in the Endo600-treated rats. Both doses of endosulfan increased the progesterone receptor (PR) expression, whereas the higher dose led additionally to an increase in estrogen receptor alpha (ERα). In the Endo600-treated rats, the down-regulation of Hoxa10 was associated with a deregulation of the steroid receptor coregulators. Alterations in endometrial proliferation and the endocrine pathway of Hoxa10/steroid receptors/coregulators might be the mechanism of endosulfan-induced implantation failure.
Assuntos
Implantação do Embrião/efeitos dos fármacos , Endossulfano/administração & dosagem , Fertilidade/efeitos dos fármacos , Inseticidas/administração & dosagem , Útero/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Carcinógenos/administração & dosagem , Carcinógenos/toxicidade , Proliferação de Células/efeitos dos fármacos , Dietilestilbestrol/administração & dosagem , Dietilestilbestrol/toxicidade , Relação Dose-Resposta a Droga , Endossulfano/toxicidade , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Inseticidas/toxicidade , Gravidez , Taxa de Gravidez , Ratos , Ratos Wistar , Esteroides/sangue , Útero/crescimento & desenvolvimentoRESUMO
Excessive use of pesticides poses increased risks to non target species including humans. In the developing countries, lack of proper awareness about the toxic potential of pesticides makes the farmer more vulnerable to pesticide linked toxicities, which could lead to diverse pathological conditions. The toxic potential of a pesticide could be determined by their ability to induce genetic mutations and cytotoxicity. Hence, determination of genetic mutation and cytotoxicity of each pesticide is unavoidable to legislate health and safety appraisal about pesticides. The objective of current investigation was to determine the genotoxic and cytotoxic potential of Endosulfan (EN) and Lambda-cyhalothrin (LC); individually and in combination. 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay was utilized to determine cytotoxicity, while two mutant histidine dependent Salmonella strains (TA98, TA100) were used to determine the mutagenicity of EN and LC. Moreover, mutagenicity assay was conducted with and without S9 to evaluate the effects of metabolic activation on mutagenicity. Even though a dose dependent increase in the number of revertant colonies was detected with EN against both bacterial strains, a highly significant (p<0.05) increase in the mutagenicity was detected in TA98 with S9. In comparison, data obtained from LC revealed less mutagenic potential than EN. Surprisingly, the non-mutagenic individual-concentrations of EN and LC showed dose dependent mutagenicity when combined. Combination of EN and LC synergistically induced mutagenicity both in TA98 and TA100. MTT assay spotlighted comparable dose dependent cytotoxicity effects of both pesticides. Interestingly, the combination of EN and LC produced increased reversion and cytotoxicity at lower doses as compared to each pesticide, concluding that pesticide exposure even at sub-lethal doses can produce cytotoxicity and genetic mutations, which could lead to carcinogenicity.
Assuntos
Sobrevivência Celular/efeitos dos fármacos , Endossulfano/toxicidade , Mutagênicos/toxicidade , Nitrilas/toxicidade , Praguicidas/toxicidade , Piretrinas/toxicidade , Testes de Carcinogenicidade , Endossulfano/administração & dosagem , Técnicas In Vitro , Testes de Mutagenicidade , Nitrilas/administração & dosagem , Piretrinas/administração & dosagemRESUMO
The decline of freshwater fish biodiversity corroborates the trends of unsustainable pesticide usage and increase of disease incidence in the last few decades. Little is known about the role of nonlethal exposure to pesticide, which is not uncommon, and concurrent infection of opportunistic pathogens in species decline. Moreover, preventative measures based on current knowledge of stress biology and an emerging role for epigenetic (especially methylation) dysregulation in toxicity in fish are lacking. We herein report the protective role of lipotropes/methyl donors (like choline, betaine and lecithin) in eliciting primary (endocrine), secondary (cellular and hemato-immunological and histoarchitectural changes) and tertiary (whole animal) stress responses including mortality (50%) in pesticide-exposed (nonlethal dose) and pathogen-challenged fish. The relative survival with betaine and lecithin was 10 and 20 percent higher. This proof of cause-and-effect relation and physiological basis under simulated controlled conditions indicate that sustained stress even due to nonlethal exposure to single pollutant enhances pathogenic infectivity in already nutritionally-stressed fish, which may be a driver for freshwater aquatic species decline in nature. Dietary lipotropes can be used as one of the tools in resurrecting the aquatic species decline.
Assuntos
Peixes , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Lipotrópicos/farmacologia , Praguicidas/toxicidade , Substâncias Protetoras/farmacologia , Estresse Fisiológico/efeitos dos fármacos , Ração Animal , Animais , Biomarcadores , Endossulfano/administração & dosagem , Endossulfano/toxicidade , Interações Hospedeiro-Patógeno/imunologiaRESUMO
Cardiovascular disease is one of the most significant causes of mortality in humans and animals, and its etiology is usually unknown. The aim of this study was to investigate the cardiac pathology of endosulfan toxicity and the protective effect of vitamin C in rabbits. Twenty-four rabbits were divided into 4 groups: (1) the END group was given a daily sublethal dose of endosulfan in corn oil by oral gavage for 6 weeks; (2) the END + C group received the endosulfan as well as vitamin C over the same 6-week period; (3) the OIL + C group received corn oil daily and vitamin C every other day; and (4) the OIL group received only corn oil daily. We observed microscopic hemorrhages, single-cell necrosis, inflammatory reactions, and fibrotic changes in the myocardium in the END group. Small hemorrhages and single-cell necrosis also were seen in some hearts in the END + C group, but no inflammation was observed. Caspase-3 immunoreactivity was more significant in myocardial cells in the END group compared with the others. A protective effect of vitamin C on lesions was observed in the END + C group. These results showed that endosulfan resulted in toxic changes in the hearts of rabbits, but this toxicity could be decreased with vitamin C treatment.
Assuntos
Apoptose/efeitos dos fármacos , Ácido Ascórbico/uso terapêutico , Cardiotoxinas/toxicidade , Endossulfano/toxicidade , Cardiopatias/prevenção & controle , Inseticidas/toxicidade , Miócitos Cardíacos/patologia , Administração Oral , Animais , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/farmacologia , Cardiotoxinas/administração & dosagem , Cardiotoxinas/farmacologia , Caspase 3/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Endossulfano/administração & dosagem , Endossulfano/farmacologia , Fibrose/induzido quimicamente , Fibrose/patologia , Fibrose/prevenção & controle , Cardiopatias/metabolismo , Cardiopatias/patologia , Inseticidas/administração & dosagem , Inseticidas/farmacologia , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Necrose/induzido quimicamente , Necrose/patologia , Necrose/prevenção & controle , CoelhosRESUMO
The genotoxic and mutagenic effects of two commonly used organochlorine pesticides, lindane (LND) and endosulfan (ENS), and two commonly used organophosphate pesticides, chlorpyrifos (CPF) and monocrotophos (MCP) were assessed using in vivo mouse bone marrow micronucleus test and in vitro Ames Salmonella/ microsome mutagenicity test. The results showed that these pesticides alone or in combination, induced significantly high frequency of micronuclei (MN) formation that increased with concentration of pesticides. All these four pesticides produced significant increase in the frequencies of micronucleated-polychromatic erythrocytes (MN-PCE) and decrease infrequencies of PCE in dose-dependent manner. The results indicate the suppression of proliferative activity of the bone marrow and increase in the extent of cell death. ENS and MCP showed mutagenic potential in Salmonella/ microsome assay. ENS induced mutagenic and nontoxic response only in TA98 tester strain of S.typhimurium at the dose of 500 µg/plate and in the absence of metabolic activation. MCP showed weak mutagenic and nontoxic effect only in TA100 tester strain at the dose of 5000 µg/plate in both assays, with or without metabolic activation when compared with negative control. MCP was toxic in TA98 tester strain at the dose of 5000 µg/plate in absence of metabolic activation while reduction in toxicity was seen on addition of S9 mixture. The study clearly showed the genotoxic potential of all these four pesticides and mutagenic response of endosulfan and monocrotophos.
Assuntos
Morte Celular/efeitos dos fármacos , Inseticidas/toxicidade , Micronúcleos com Defeito Cromossômico/efeitos dos fármacos , Mutagênicos/toxicidade , Animais , Medula Óssea/efeitos dos fármacos , Medula Óssea/metabolismo , Clorpirifos/administração & dosagem , Clorpirifos/toxicidade , Relação Dose-Resposta a Droga , Endossulfano/administração & dosagem , Endossulfano/toxicidade , Hexaclorocicloexano/administração & dosagem , Hexaclorocicloexano/toxicidade , Inseticidas/administração & dosagem , Masculino , Camundongos , Testes para Micronúcleos , Microssomos , Monocrotofós/administração & dosagem , Monocrotofós/toxicidade , Testes de Mutagenicidade , Mutagênicos/administração & dosagem , Ratos , Ratos Wistar , Salmonella/genéticaRESUMO
This study is aimed at evaluating the sublethal effects of endosulfan (EDS) in juvenile common carp (Cyprinus carpio). For this purpose, fish were exposed for 15 days to the technical EDS (95% pure) diluted in dimethyl sulfoxide (DMSO) 0.1% of the total volume in water solution in a semi-static system at sublethal concentration (1 µg/L). Subsequently, the liver somatic index (LSI) and factor condition (K) were determined. The total cytocrome P450 (CYP), CYP1A isoform, and the ethoxyresorufin-O-deethylase (EROD) activity were determined from the hepatic microsomal fraction as well as the activity of the oxidative stress enzyme system such as superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GP(X)), glutathione reductase (GR), and glucose-6-phosphate dehydrogenase (G6PDH). Among the parameters assessed, EDS at the sublethal concentration in subchronic exposure caused significant changes in liver somatic indices as well as induction of the phase I biotransformation system and oxidative stress in juvenile common carp (Cyprinus carpio). Thus, it is seen that the use of biochemical biomarkers of environmental contamination in this study proved to be an extremely important tool for detecting the adverse effects of xenobiotics in the aquatic environment, even at low concentration.
Assuntos
Carpas/metabolismo , Endossulfano/toxicidade , Inseticidas/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Biomarcadores/metabolismo , Citocromo P-450 CYP1A1/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Endossulfano/administração & dosagem , Proteínas de Peixes/metabolismo , Inseticidas/administração & dosagem , Fígado/efeitos dos fármacos , Fígado/enzimologia , Microssomos/efeitos dos fármacos , Microssomos/enzimologia , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/administração & dosagemRESUMO
An increasing number of studies have documented that sublethal pesticide exposure can change predator-prey interactions. Most of these studies have focused on effects of long-term pesticide exposure on only one type of antipredator traits and have not directly linked changes in these traits to mortality by predation. To get a better mechanistic understanding of how short-term pesticide pulses make prey organisms more vulnerable to predation, we studied effects of 24h exposure to a sublethal concentration of the insecticide endosulfan and the herbicide Roundup on the major antipredator traits and the resulting mortality by predation in larvae of the damselfly Enallagma cyathigerum. A pulse of both pesticides affected antipredator traits involved in avoiding detection by predators as well as traits involved in escape after detection. After a pesticide pulse, larvae increased activity levels and even further increased the number of walks when predation risk was present. Further, an endosulfan pulse tended to reduce escape swimming speed. In contrast, previous exposure to Roundup caused the larvae to swim faster, yet less often when attacked. Importantly, although both studied pesticides induced maladaptive changes in overall activity, only for endosulfan this resulted in an increased mortality by predation. Our study highlights that considering changed predator-prey interactions may improve ecological risk evaluations of short pesticide pulses, yet also underscores the need (1) to consider effects on all important antipredator traits of the prey as trait compensation may occur and (2) to effectively score the outcome of predator-prey interactions in staged encounters.
Assuntos
Endossulfano/toxicidade , Reação de Fuga/efeitos dos fármacos , Insetos/fisiologia , Inseticidas/toxicidade , Animais , Endossulfano/administração & dosagem , Feminino , Insetos/efeitos dos fármacos , Inseticidas/administração & dosagem , Estresse Fisiológico , Natação , Poluentes Químicos da Água/administração & dosagem , Poluentes Químicos da Água/toxicidadeRESUMO
Endosulfan is an organochlorine pesticide, which is used worldwide and has known toxic effects on non-target organisms including fish. This research investigated the acute and chronic effects of pulse-exposed endosulfan on Florida flagfish (Jordanella floridae). A 4-h pulse-exposure of endosulfan to larval flagfish caused a significant increase in mortality after 96 h at nominal concentrations equal to or greater than 100 µg/L. Some of the acute sub-lethal observations included hyperactivity, convulsions, and axis malformation. Seven-eight day old post-hatch flagfish were pulse-exposed for 4h to endosulfan and then monitored over one full life-cycle for chronic effects on growth, reproduction, and survivability. There were no growth or reproductive effects of endosulfan pulse-exposure up to the highest exposure concentration of 10.8 µg/L. Thus, the life-cycle 4-h pulse-exposure no observed effect concentration (NOEC) and lowest observed effect concentration (LOEC) were 3.3 and 10.8 µg/L endosulfan, respectively, based on significantly higher larval and juvenile mortality.