Functional role of phospholipase D (PLD) in di(2-ethylhexyl) phthalate-induced hepatotoxicity in Sprague-Dawley rats.
نویسندگان
چکیده
Phospholipase D (PLD) is an enzyme that catalyzes the hydrolysis of phosphatidyl choline (PC) to generate phosphatidic acid (PA) and choline. PLD is believed to play an important role in cell proliferation, survival signaling, cell transformation, and tumor progression. However, it remains to be determined whether enhanced expression of PLD in liver is sufficient to induce hepatotoxicity. The aim of this study was to investigate the possible role of PLD in di(2-ethylhexyl) phthalate (DEHP)-induced hepatotoxicity in Sprague-Dawley rats. The phthalate, DEHP (500 mg/kg/d), was administered orally, daily to prepubertal rats (4 wk of age, weighing approximately 70-90 g) for 1, 7, or 28 d. In this study, protein expression levels of PLD1/2, peroxisome proliferator-activated receptor (PPAR), and cytochrome P-450 (CYP) were determined by Western blot analysis using specific antibodies. Liver weight was significantly increased in the DEHP treatment groups. Immunohistochemical analysis demonstrated that DEHP produced strong staining of proliferating cell nuclear antigen (PCNA) at 28 d of exposure, suggestive of hepatocyte proliferation. A significant rise in PLD1/2 expression was observed in liver of DEHP-exposed rats after 7 d. Further, PPARα, constitutive androstane receptor (CAR), pregnane X receptor (PXR), and CYP2B1 protein expression levels were markedly elevated in DEHP-treated groups. Our results suggest that DEHP significantly enhanced the expression of PLD, which may be correlated with PPARα-induced hepatotoxicity through a complex interaction with nuclear receptors including CAR and PXR.
منابع مشابه
Prevention of di (2-ethylhexyl) Phthalate-induced Testicular Disturbance in Mice by Co-administration of L-carnitine
متن کامل
Di-(2-ethylhexyl) phthalate induces precocious puberty in adolescent female rats
Objective(s): Nowadays, Di-(2-ethylhexyl) phthalate (DEHP) is widely used in different kinds of commercial products as a plasticizer. Previous studies have revealed that exposures to DEHP could be associated with precocious puberty in teenagers, but the exact mechanism is yet to be known. Materials and Methods: In this study, 48 prepubertal Wistar female rats were randomly apportioned into 4 gr...
متن کاملComparison of the Short Term Toxicity of Phthalate Diesters and Monoesters in Sprague-Dawley Male Rats
This study was carried out to investigate the short term toxicity of nine phthalate diesters including di-2 (ethylhexyl) phthalate (DEHP) , di (n-butyl) phthalate (DBP) , di-n-octyl phthalate (DnOP) , diethyl phthalate (DEP) , butylbenzyl phthalate (BBP) , dimethyl phthalate (DMP) , di-isodecyl phthalate (DIDP) , diundecyl phthalate (DUP) , and di-isononyl phthalate (DINP) and five phthalate mo...
متن کاملDopamine-Induced Plasticity, Phospholipase D (PLD) Activity and Cocaine-Cue Behavior Depend on PLD-Linked Metabotropic Glutamate Receptors in Amygdala
Cocaine-cue associations induce synaptic plasticity with long lasting molecular and cellular changes in the amygdala, a site crucial for cue-associated memory mechanisms. The underlying neuroadaptations can include marked alterations in signaling via dopamine (DA) receptors (DRs) and metabotropic glutamate (Glu) receptors (mGluRs). Previously, we reported that DR antagonists blocked forms of sy...
متن کاملChronic Effects of Di(2-ethylhexyl)phthalate on Stereological Parameters of Testis in Adult Wistar Rats
Objective(s) In recent years concerns have been raised regarding the incidence of male reproductive disorders from exposure to endocrine disruptors. So, chronic effects of di(2-ethylhexyl)phthalate were studied on histological and stereological structure of testis in adult Wistar rats. Materials and Methods Thirty two adult Wistar rats were randomly divided in four equal experiment groups; o...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Journal of toxicology and environmental health. Part A
دوره 73 21-22 شماره
صفحات -
تاریخ انتشار 2010