ABSTRACT
Di-n-butyl phthalate (DBP), one of the plasticizers, is considered a ubiquitous environmental contaminant due to its widespread application in personal-care products and serves as a raw material in many industries for the generation of many plastic products. Several scientific investigations have shown that DBP caused embryotoxicity and cognitive impairments. However, there is less understanding of the genotoxic potential of DBP in neuronal tissue when exposure happens continuously for several generations. The present study was undertaken to investigate the impact of DBP on the nucleic acids of neuronal tissue in one-month-old rats by performing a comet assay and biochemical analyses. By oral gavage, the parental generation (F0) was administered DBP (500 mg/kg/day) during gestation (GD6-20) and lactation, and exposures were continued for three consecutive generations until the pups were grown to one-month-old. The oxidative stress assessments carried out in discrete brain regions isolated from one-month-old rats (F1-F3) following DBP exposure indicated significant inhibition in the levels of antioxidant enzymes (superoxide dismutase and catalase) while oxidant status (malondialdehyde) was elevated significantly. The extent of DNA damage using the comet assay, as measured by the olive moment, tail DNA percentage and tail length, was greater in DBP-treated rats compared with the control group, but RNA/DNA content decreased significantly. The results of this study suggested a strong link between oxidative stress and genetic integrity in the neuronal tissue of rats exposed to DBP generationally. To summarise, DBP exposure during pregnancy caused oxidative stress, which resulted in genetic instability in specific discrete brain regions of the third generation.
Subject(s)
DNA Damage , Dibutyl Phthalate , Prenatal Exposure Delayed Effects/pathology , Animals , DNA , Dibutyl Phthalate/toxicity , Female , Malondialdehyde , Pregnancy , Rats , Rats, WistarABSTRACT
The extensive use of di--n-butyl phthalate (DBP) as a plasticizer in medical devices, personal care products, and industries, which is a major threat to humankind as it leaches out easily from the plastic matrix into the environment. Health risks posed to adults and children from the broad usage of DBP in cosmetics and infant toys observed predominantly due to repeated and prolonged exposure. Hence, this study was undertaken to evaluate the potential effect of DBP in the hepatic tissue of rats up to three generations. Wistar rats were induced at a dose of 500 mg DBP /kg body weight dissolved in olive oil by oral gavage throughout gestation (GD 6-21), lactation and post-weaning and reared by crossing intoxicated rats up to three generations. Results of the present study showed a significant increase in the relative weight of liver, while decreased levels of antioxidant enzymes viz., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH) was evident in DBP treated rats at P < 0.05. Besides hepatic marker enzymes viz., alanine transaminase (ALT) and aspartate transaminase (AST) were elevated significantly in experimental rats compared to those of the control group. Furthermore, histological studies revealed congested central veins and dilated sinusoids in F1 progeny while mild to severe focal inflammatory infiltrations were evident in F2 & F3 rats. Negative correlation observed between the levels of antioxidant enzymes and transaminase activity. In brief, DBP exposure elicits oxidative stress and alters the transaminase activity levels causing damage in hepatic tissue. F3 progeny found to high vulnerability to the exposure of DBP than F2 & F1 rats.
ABSTRACT
With the limited but ongoing usage of di-n-butyl phthalate (DBP) as plasticizer, the health effects of both phthalate and its alternatives are far from being understood. Multigenerational effects of phthalates were evaluated in rats upon exposure to DBP, aiming to provide some evidences about its potential in causing developmental teratogenicity. Gestational rats were exposed to DBP (500 mg/kg bw/day) and control groups with olive oil. On the 18th day of gestation, fetuses (F1) isolated from a few dams were subjected to prenatal screening, and the other rats were allowed to litter, and later postnatal screening was made. DBP-toxicated (F1) rats were crossed and reared up to three generations (F2 and F3) by adopting the same experimental design. A considerable decrease in the weight of placenta, low number of corpora lutea and increased resorptions, and pre- and postimplantation loss were observed in F1, F2, and F3 generations. Further, there was a decrease in the number of live births and fetal body weight with high mortality, the developmental indices showed reduction in litter size and sex ratio, and a considerable incidence of skeletal and malformation complex involving face and eye was observed in later generations compared to the first. The pre-weaning indices in neonates showed a considerable delay in physical growth milestones and poor scores in sensory motor development. Alterations noticed in the levels of thyroid profile and testosterone found to have a role in sensory motor, craniofacial development, and eye formation. In brief, results confirm multigenerational and fetotoxic effects of DBP; thereby, findings imply that developing tissues are the targets and endocrine disruption appears to be the underlying mechanism of phthalate action.
