RESUMO
Some pesticides increase the risk of type 2 diabetes, but whether fetal exposure carries transgenerational risk remains unknown. We evaluated the metabolic effects of gestational exposure to chlorpyrifos and imidacloprid in female Wistar rats and their offspring. We studied female nulliparous Wistar rats, including six exposed to imidacloprid (IMI) and six to chlorpyrifos (CPF) once daily throughout gestation at 1/10 lethal dose 50, while six (control group) received distilled water. These were explored 1 month after the birth of the offspring, while their offspring were explored at weaning (4 weeks) and adult age (12 weeks). Blood glucose, insulin and lipid profile were determined at each stage, while glucose transporter 4 (GLUT4) and nuclear factor kappa beta (NFkß) protein expression was measured in skeletal muscle at the end of follow up. Exposure to pesticides was associated with significantly higher fasting glucose (+25.4 to 30.9%) and insulin (> 100%) levels, with > 100% increased insulin resistance (HOMA-IR), - 18.3 to - 21.1% reduced HDL-cholesterol and + 60.9 to + 102.6% increased LDL-cholesterol in mothers. GLUT4 expression was reduced by 28.9-42.3% while NFkß expression increased by 32.8-35.4% in mothers. In offspring, similar abnormalities were observed at weaning (+ 18.4 to 67.4% fasting glucose, + 57.1 to 72.2% LDL-cholesterol, + 72.3 to 78.2% fasting insulin), persisting at adult age with decreased expression of GLUT4 (- 52.8 to 54.5%) and increased expression of NFkß (+ 30.5 to 30.7%). Gestational exposure to imidacloprid and chlorpyrifos induces hyperglycemia, insulin resistance and dyslipidemia in female Wistar rats and their offspring. The effects on offspring persist until adult age, suggesting intergenerational adverse effects.
RESUMO
Pesticide exposure may induce biochemical alterations including oxidative stress and lipid peroxidation. However, in the context of developmental origin of health and disease, putative trans-generational effect of exposure to pesticides are insufficiently studied. We therefore aimed to evaluate the biochemical effect of gestational exposure to four pesticides on female Wistar rats and their offspring at adult age. We studied 30 female nulliparous Wistar rats divided into 5 equal groups. Group 1 served as the control group and received distilled water while group 2, 3, 4 and 5 received orally pesticide 1 (imidacloprid), pesticide 2 (chlorpyrifos), pesticide 3 (imidacloprid + lambda cyhalothrin) and pesticide 4 (oxamyl) respectively once daily throughout gestation at a dose equivalent to 1/10 lethal dose 50. The mothers were followed up until one month post gestation. The offspring were followed up from birth until adult age (12 weeks). In all animals at each time point we evaluated malondialdehyde (MDA), oxidative stress and liver function enzymes. There was similar variation of total body weight in all the groups during and after gestation. However, Female Wistar rats of the exposed groups had significant alterations in liver SOD (-30.8% to +64.1%), catalase (-38.8% to -85.7%) and GSH (-29.2% to -86.5%) and; kidney catalase (> 100%), GSH (> 100%). Moreover, MDA, alanine transaminase (ALT) and aspartate transaminase (AST) levels were significantly higher in pesticide exposed rats compared to the control group. Similar alterations in antioxidant enzymes, MDA and liver function enzymes were observed in offspring of treated rats evidenced at weaning and persisting until adult age. Exposure to pesticides causes oxidative stress and lipid peroxidation in exposed female Wistar rats and their offspring. The persistence in offspring at adult age suggests transgenerational adverse effects.