ABSTRACT
PURPOSE: Nonylphenol (NP) is one widely distributed representative of environmental estrogens that disturb reproductive activities, bone metabolism and brain function through interfering diverse signal pathways leading to hormone metabolic dysfunctions, immunologic derangement, and tumorigenesis. Few of previous studies have observed the subacute toxicity on rodents, and little has been focused on the mechanism underneath the toxicities observed. METHODS: The 32 male Sprague-Dawley (SD) rats were randomly divided into four groups, the negative control group (corn oil) NP low, medium and high dose groups [30, 90, 270 mg/(kg·d)]. SD rats administrated with different dosage of NP every other day for 28d. Elisa and RT-PCR was employed to observe estrogen metabolism markers or mRNA expressions. RESULTS: In serum, NP exposure caused testosterone (T) (pâ¯<â¯0.001), progesterone (PROG) (pâ¯<â¯0.05) and estrone (E1) (pâ¯<â¯0.05) increased. In testicle, NP exposure caused T (pâ¯<â¯0.001), PROG (pâ¯<â¯0.05), E1 (pâ¯<â¯0.05), 17ß-estradiol (E2) (pâ¯<â¯0.05) and ERα mRNA (pâ¯<â¯0.01) increased, while P450 aromatizing enzyme (pâ¯<â¯0.001) decreased in NPL and ERß mRNA (pâ¯<â¯0.001) decreased in NPM and NPH. In liver, NP exposure caused 17ß-HSD2 mRNA (pâ¯<â¯0.01) increased, while P450 aromatizing enzyme decreased (pâ¯<â¯0.05). CONCLUSION: NP exposure exhibited general and estrogenic toxicity in rats through disturbing estrogen secretion network and estrogen receptor expression network, inducing abnormal metabolism of estrogen, whether in serum, liver and testicle.
Subject(s)
Endocrine Disruptors/toxicity , Estrogens/metabolism , Liver/metabolism , Phenols/toxicity , Testis/metabolism , Animals , Cytochrome P-450 Enzyme System/metabolism , Estradiol/metabolism , Estrogen Receptor alpha/metabolism , Estrogen Receptor beta/metabolism , Estrone/metabolism , Female , Male , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Receptors, Estrogen/metabolism , Testosterone/metabolism , Toxicity TestsABSTRACT
BACKGROUND: Di(2-ethylhexyl) phthalate (DEHP) is one of the most widely used phthalate esters. The application of DEHP has caused serious environmental pollution and posed a threat to human health. METHODS: A total of 30 male Sprague-Dawley rats were randomly divided into control group, DEHP group (500 mg/kg DEHP), low GABA (Gama-aminobutyric acid) group (500 mg/kg DEHP and 1 mg/kg GABA), medium GABA group (500 mg/kg DEHP and 2 mg/kg GABA) and high GABA group (500 mg/kg DEHP and 4 mg/kg GABA). The interventions continued for 30 consecutive days. Open-field test and elevated plus-maze test were used to detect behavioral changes of rats before and after interventions. RESULTS: The levels of nitric oxide and nitric oxide synthase in prefrontal cortex of rats were measured using enzyme-linked immunosorbent assay. DEHP and GABA treatment had no significant effects on the body weight of rats. GABA restored food utilization rate of rats impaired by DEHP to the level of healthy rats. According to open-field test and elevated plus-maze test, GABA alleviated the effects of DEHP on rat behaviors. Enzyme-linked immunosorbent assay showed that GABA was effective in reducing the levels of nitric oxide and nitric oxide synthase in rats treated with DEHP. CONCLUSION: DEHP exposure induced anxiety in rats, which may be achieved through elevating nitric oxide and nitric oxide synthase levels in prefrontal cortex of rats. However, the effects caused by DEHP could be alleviated by GABA.
Subject(s)
Anxiety , Behavior, Animal , Diethylhexyl Phthalate , GABA Agents , Nitric Oxide Synthase , Nitric Oxide , Prefrontal Cortex , gamma-Aminobutyric Acid , Animals , Rats , Anxiety/chemically induced , Anxiety/drug therapy , Behavior, Animal/drug effects , Diethylhexyl Phthalate/administration & dosage , Diethylhexyl Phthalate/pharmacology , GABA Agents/administration & dosage , GABA Agents/pharmacology , gamma-Aminobutyric Acid/administration & dosage , gamma-Aminobutyric Acid/pharmacology , Nitric Oxide/metabolism , Nitric Oxide Synthase/metabolism , Prefrontal Cortex/drug effects , Prefrontal Cortex/metabolism , Random Allocation , Rats, Sprague-DawleyABSTRACT
Nonylphenol (NP) and octylphenol (OP) are priority environmental contaminants that have a potential role as endocrine disruptors. They can be biomagnified in the food chain and pose an estrogenic health risk to human health. A 28-day oral toxicity study was performed to observe the impact of single and combined exposure to NP and OP on 5-HT transporter (SERT) as well as 5-HT2A receptor. Results showed that the 5-HT levels in rat plasma increased with exposure to middle-dose and high-dose NP, to high-dose OP, and to low, middle, and high doses of combined NP and OP (P < 0.05), while the 5-HT levels in rat platelets increased when exposed to NP/OP or combined NP and OP of middle or high dose (P < 0.05). The expression levels of SERT in rat platelets decreased when exposed to high-dose NP/OP or high dose of combined NP and OP (P < 0.05). Meanwhile, the expression levels of 5-HT2A in rat platelets decreased when exposed to high-dose NP/OP as well as combined NP and OP (P < 0.05). These findings suggested that exposure to NP and OP could influence the metabolic network of 5-hydroxytryptamine via transportation and receptor binding pathways.