RESUMEN
In view of the increased use of anilofos for crop protection and ever increasing arsenic levels in drinking water in many countries, the coexistence of arsenic and anilofos in the environment is a reality and simultaneous exposure of humans and animals to these contaminants could be potentially hazardous. The aim of the present study was to examine whether coexposure to arsenic at the groundwater contamination level could alter the embryofetal toxicity of anilofos in rat model. Anilofos (100 mg kg(-1) day(-1)) and sodium arsenite (1 mg arsenic kg(-1) day(-1)) were administered by gavage either individually or in combination to the pregnant rats from day 6 to day 15 of gestation. Arsenic did not produce any significant effects either on maternal or fetal parameters at the given dose. Anilofos alone significantly decreased maternal weight gain, feed and water intakes, gravid uterine weights, number of live fetuses and fetal body weights and increased resorptions. There were increased incidences of gross, skeletal and visceral anomalies in the fetuses of anilofos-treated group. The main skeletal abnormality was increased intercostal space, while the visceral anomaly was an interventricular septal defect. Treatment with the combination of arsenic and anilofos significantly enhanced the fetal changes with much greater magnitude compared with the effects produced by anilofos alone. Anomalies such as midfacial cleft, exencephaly and anophthalmia were seen only in the fetuses of the combination group. The results show that anilofos interferes with embryofetal development and coexposure with arsenic at environmentally realistic concentrations produces additive or synergistic effects on the developmental toxicity of anilofos in rats.
Asunto(s)
Arsenitos/toxicidad , Desarrollo Embrionario/efectos de los fármacos , Compuestos Organofosforados/toxicidad , Compuestos de Sodio/toxicidad , Anomalías Inducidas por Medicamentos/etiología , Anomalías Inducidas por Medicamentos/patología , Animales , Arsenitos/administración & dosificación , Relación Dosis-Respuesta a Droga , Ingestión de Líquidos/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Implantación del Embrión/efectos de los fármacos , Pérdida del Embrión/inducido químicamente , Exposición a Riesgos Ambientales/análisis , Femenino , Edad Gestacional , Humanos , Intubación Gastrointestinal , Compuestos Organofosforados/administración & dosificación , Embarazo , Ratas , Ratas Wistar , Compuestos de Sodio/administración & dosificación , Abastecimiento de Agua/análisis , Aumento de Peso/efectos de los fármacosRESUMEN
To elucidate the teratogenic effects, ochratoxin A (OTA) and aflatoxin B1 (AFB1) were dissolved in corn oil and administered in combination to New Zealand White rabbits during 6-18 days of gestation orally with the dose levels of OTA+AFB1, 0.05+0.05 and 0.1+0.1mg/kg body weight. To assess pathomorphological features of the anomalies, the fetal serial sections were histologically examined. There was no mortality in any of the treated groups. Body weights and body weight gains of dams in the combined treatment groups were comparable with those of controls and individual treatments. The mean crown to rump lengths in both the combination dose groups and mean fetal weights in high dose combination group were significantly decreased. In the high dose combination, there was increase in the percent of implants resorbed and significant increase in the incidence of visceral anomalies. The combination treatment resulted in various gross, skeletal and visceral anomalies such as wrist drop, scoliosis, bent metacarpals, rudimentary ribs, cardiac defects and microphthalmia. There was a dose-related increase in the percent of litters showing the histopathological changes in the fetal tissues. The incidence of histopathological changes in the tissue sections prepared from fetal liver, kidneys, brain, heart and eyes was found increased in the high dose combination group. The comparative evaluation of the results of combination versus individual treatments revealed that certain anomalies observed in the individual treatment of OTA such as knuckling of fetlock, rudimentary tail or agenesis of tail, wavy ribs, hydrocephalus and agenesis of kidney and AFB1 as enlarged eye sockets and enlarged liver were absent in the combination treatment. However, some new manifestations such as cardiac defects and scoliosis were seen. The results of the present study indicated that in combination, OTA and AFB1 have antagonistic interaction. The presence of subtle lesions histologically due to an interference with normal development suggested that microscopic examination of the fetal tissues could provide additional, useful information to a developmental toxicity study.
Asunto(s)
Aflatoxina B1/toxicidad , Anomalías Congénitas/patología , Feto/patología , Ocratoxinas/toxicidad , Organogénesis/efectos de los fármacos , Teratógenos/toxicidad , Animales , Anomalías Congénitas/embriología , Anomalías Congénitas/etiología , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Femenino , Feto/efectos de los fármacos , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal , ConejosRESUMEN
Aflatoxin B1 (AFB1), is a food borne mycotoxin produced by fungal species of the genera Aspergillus. To elucidate the teratogenic effects, AFB1 was dissolved in corn oil and given orally to New Zealand White rabbits during 6-18 days of gestation with the dose levels of 0.025, 0.05 and 0.1 mg/kg body weight. To assess pathomorphological features of the anomalies induced by AFB1, the fetal serial sections were histologically examined. There was no maternal mortality in any group. There was non-significant decrease in percent of live fetuses and increase in the percent resorptions and post-implantation losses at 0.1 mg/kg dose group as compared with those of controls. The mean crown to rump lengths of 0.05 and 0.1 mg/kg dose groups were significantly reduced than that of the control. The mean fetal weights were significantly reduced in 0.1 mg/kg dose group than that of other treated groups. The gross anomalies observed included wrist drop and enlarged eye socket whereas, skeletal anomalies were agenesis of caudal vertebrae, incomplete ossification of skull bones and bent metacarpals. The visceral anomalies of microphthalmia and cardiac defects were seen at 0.1 mg/kg dose group. The characteristic histological findings of fetal tissues were distortion of normal hepatic cord pattern and reduced megakaryocytes in liver, fusion of auriculo-ventricular valves, mild degenerative changes in myocardial fibers, microphthalmic eyes and lenticular degeneration. The results of this study indicated that AFB1 was found to be teratogenic in rabbits when given by oral route during gestation days 6-18 and the dose of 0.1 mg/kg could be considered as the minimum oral teratogenic dose. The histological examination of the fetal tissues indicated its importance in identifying the visceral anomalies which were otherwise not visible.
Asunto(s)
Aflatoxina B1/toxicidad , Anomalías Congénitas/etiología , Desarrollo Embrionario/efectos de los fármacos , Administración Oral , Aflatoxina B1/administración & dosificación , Animales , Anomalías Congénitas/veterinaria , Relación Dosis-Respuesta a Droga , Femenino , Embarazo , ConejosRESUMEN
Ochratoxin A (OA) and Aflatoxin B1 (AFB1), the food borne mycotoxins are produced by several fungal species of the genera Aspergillus and Penicillium. To determine the teratogenic effects, these mycotoxins were administered orally either individually or in combination to the pregnant Wistar rats on days 6-15 of gestation. OA and AFB1 were dissolved in corn oil and different doses of OA (0.125, 0.25, 0.50, and 0.75 mg/kg), AFB1 (0.125, 0.25, 0.50, and 1.00 mg/kg), and a combination of OA+AFB1 (0.125+0.125; 0.25+0.50; 0.50+0.25 mg/kg) were given by gastric intubation to rats. During dosing period, the body weight and body weight gains significantly decreased at a higher dosage, in both individual and combined treatments. In all the combination treatments, the percent implants resorbed, fetal body weights, and crown-rump lengths were comparable to those of controls and with the individual mycotoxin treatment. The number of dead fetuses was significantly increased in the high OA combination (OA+AFB1 0.50+0.25) group as compared with the other two combinations. OA and AFB1 alone and in combination caused various gross, skeletal, and visceral anomalies. The occurrence was considerably less pronounced in fetuses of AFB1 and combination groups as compared with those of OA group fetuses. The exencephaly, incomplete closure of skull, wavy and fused ribs, agenesis of the ischium bone, and enlarged renal pelvis, recorded in OA treatment and ear abnormality and incomplete ossification of skull bones observed in AFB1 when given individually, were not seen in combination groups. However, new manifestations, such as gastroschisis and syndactyly were observed and the incidence of cardiac defects was increased in fetuses due to the combined treatment. The results of the present study indicated that there is some interaction between these mycotoxins that resulted in reduced teratogenic activity of OA in the presence of AFB1. Apparently, new manifestations observed in combination treatment points to the potential threat of teratogenicity in terms of public health hazards.
Asunto(s)
Anomalías Inducidas por Medicamentos/etiología , Aflatoxina B1/toxicidad , Carcinógenos/toxicidad , Desarrollo Embrionario/efectos de los fármacos , Exposición Materna , Ocratoxinas/toxicidad , Animales , Peso Corporal/efectos de los fármacos , Huesos/anomalías , Combinación de Medicamentos , Femenino , Muerte Fetal , Micotoxinas/toxicidad , Embarazo , Ratas , Ratas WistarRESUMEN
The histopathological features of various abnormalities induced by different doses of ochratoxin A (OA), aflatoxin B1 (AFB1), and their combination in rat fetuses were studied. The pregnant Wistar rats were orally treated during 6-15 gestation days with different doses of OA (0.125, 0.25, 0.50, 0.75 mg/kg), AFB1 (0.125, 0.25, 0.50, 1.00 mg/kg), and their combination (0.125+0.125, 0.25+0.50, 0.50+0.25 mg/kg). The fetal sections passing through liver, kidney, brain, heart, and eyes were selected from the fetuses given visceral examination representing each litter. The selected sections were processed for paraffin embedding, stained with H and E, and examined by light microscopy. The histological examination of the fetal organs revealed that OA, AFB1, and their combination treatments caused variable changes in internal organs. In the case of OA, the incidence of pathological lesions liver, kidney, brain, and eye lesions was high, whereas in AFB1 treatment, liver, brain, kidney, and heart were affected. The incidence of heart lesions, especially valvular defects, increased in the combination groups. Bile duct proliferation/new bile duct formation, defective ossification of cranial bones, exposure of the brain to the exterior, hypoplasia of cerebellum, and retinal defects observed in OA treatment and spinal cord defects in addition to liver, kidney, and brain changes observed in AFB1 were less severe in the combination groups. The present study indicates that the occurrence of brain, kidney, and liver lesions in combination treatment was less than in either individual treatment suggesting antagonism of OA-induced teratogenic effects by AFB1. The indication of subtle lesions due to an interference with normal development and arrest of differentiation in various internal organs observed in the present study suggests that microscopic examination of the tissues can provide additional useful information to a developmental toxicity study.