Antioxidant effect of ascorbic acid on PCB (Aroclor 1254) induced oxidative stress in hypothalamus of albino rats

Muthuvel, R.; Venkataraman, P.; Giribabu, K.; Gunadharini, Dharmalingam Nandagopal; Palaniyandi, Kanagaraj; Stanley, Jone A.; Srinivasan, Narasimhan; Balasubramanian, K.; Aruldhas, M. M.; Arunakaran, J.

doi:10.1016/j.cca.2005.09.006

Cited by 72 publications

(42 citation statements)

References 44 publications

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“…LH secretion is regulated by gonadotropin-releasing hormone released from the hypothalamus. Previous studies from our laboratory demonstrated that PCB altered the hypothalamicpituitary-testicular axis in adult rats (Murugesan et al 2005c, Muthuvel et al 2006.…”

Section: Introductionmentioning

confidence: 82%

Effects of polychlorinated biphenyl (Aroclor 1254) on steroidogenesis and antioxidant system in cultured adult rat Leydig cells

Palaniappan¹,

Balaganesh²,

Balasubramanian³

et al. 2007

Journal of Endocrinology

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Polychlorinated biphenyls (PCBs) are ubiquitous and persistent environmental contaminants that disturb normal endocrine functions, including gonadal functions in humans and mammals. In the present study, we examined the direct effects of PCB on rat Leydig cells in vitro. Adult Leydig cells were purified by Percoll gradient centrifugation method and the purity of Leydig cells was also determined by 3b-hydroxysteroid dehydrogenase (3b-HSD) staining method. Purified Leydig cells were exposed to different concentrations (10 K10-10 K7 M) of PCB (Aroclor 1254) for 24 h under basal and LH-stimulated conditions. After the experimental period, cultured media were collected and used for the assay of testosterone and estradiol. The treated cells were used for the quantification of cell-surface LH receptors and activities of steroidogenic enzymes, such as cytochrome P 450 side-chain cleavage enzyme (P 450 scc), 3b-HSD, and 17b-hydroxysteroid dehydrogenase (17b-HSD). Leydig cellular enzymatic antioxidants, such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, g-glutamyl transpeptidase, glutathione-S-transferase, and nonenzymatic antioxidants, such as vitamins C and E, were assayed. Lipid peroxidation (LPO) and reactive oxygen species (ROS) were also estimated in Leydig cells. In addition, total RNA was isolated from control and Aroclor 1254-exposed Leydig cells to monitor the steady-state mRNA levels by reverse transcription(RT)-PCR for steroidogenic acuteregulatory (StAR) protein, cytochrome P 450 scc, 3b-HSD, and 17b-HSD. Our results indicated that Aroclor 1254 (10 K9 , 10 K8 , and 10 K7 M) treatments significantly inhibit basal and LH-stimulated testosterone and estradiol production. In addition, the activities of steroidogenic enzymes, enzymatic and nonenzymatic antioxidants were significantly diminished in a dose-dependent manner. However, LPO and ROS were elevated in a dose-dependent manner under basal and LH-stimulated conditions. RT-PCR analysis of StAR mRNA level showed a decrease only in 10 K7 M dose of Aroclor 1254 treatment, while cytochrome P 450 scc, 3b-HSD, and 17b-HSD mRNAs were drastically decreased in both 10 K8 and 10 K7 M Aroclor 1254 treatment. These findings suggest that PCBs can act directly on Leydig cells to diminish testosterone production by inhibiting gene expression of steroidogenic enzymes and antioxidant system.

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Section: Introductionmentioning

confidence: 82%

Effects of polychlorinated biphenyl (Aroclor 1254) on steroidogenesis and antioxidant system in cultured adult rat Leydig cells

Palaniappan¹,

Balaganesh²,

Balasubramanian³

et al. 2007

Journal of Endocrinology

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“…Lee and Opanashuk (2004) have shown that PCB exposure in MN9D DA cell lines results in the formation of oxidative products and depletion of intracellular GSH while Lee et al (2006) suggested that PCB-induced increases in heme-oygenase-1 and corresponding increases in Fe 2+ at least partly explain the PCB-induced oxidative stress and eventual toxicity reported earlier. In vivo, rats exposed to A1254 have increased levels of oxidative damage (e.g., increased lipid peroxidation and H 2 O 2 , as well as decreased GSH) in a number of brain regions; interestingly, vitamin C treatment protected against these effects, although the exact mechanism of the changes was not explored (Muthuvel et al, 2006;Venkataraman et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…In fact, when the MN9D DA cell line was exposed to PCBs, neuronal death ensued, arising from increased oxidative stress (Lee and Opanashuk, 2004;Lee et al, 2006). Recently, rats exposed to PCBs, were found to have decreased levels of glutathione, a major cellular antioxidant, as well as increased levels of lipid peroxidation products and hydrogen peroxide (H 2 O 2 ) in several brain regions (Muthuvel et al, 2006;Venkataraman et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Polychlorinated biphenyl-induced oxidative stress in organotypic co-cultures: Experimental dopamine depletion prevents reductions in GABA

Lyng

Seegal

2008

NeuroToxicology

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Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that have been demonstrated to be toxic to the dopamine (DA) systems of the central nervous system. One proposed mechanism for PCB-induced DA neurotoxicity is inhibition of the vesicular monoamine transporter (VMAT); such inhibition results in increased levels of unsequestered DA and DA metabolism leading to oxidative stress. We have used an organotypic co-culture system of developing rat striatum and ventral mesencephalon (VM) to determine whether alterations in the vesicular storage of DA, resulting from PCB exposure and consequent induction of oxidative stress, leads to GABA and DA neuronal dysfunction. 24 hr exposure to an environmentally relevant mixture of PCBs reduced tissue DA and GABA concentrations, increased medium levels of DA and measures of oxidative stress in both the striatum and VM. Alterations in neurochemistry and increases in measures of oxidative stress were blocked in the presence of n-acetylcysteine (NAC). Although NAC treatment did not alter PCB-induced changes in DA neurochemistry, it did protect against reductions in GABA concentration. To determine whether alterations in the vesicular storage of DA were responsible for PCB-induced oxidative stress and consequent reductions in GABA levels, we depleted DA from the co-cultures using α-methyl-p-tyrosine (AMPT). AMPT reduced striatal and VM DA levels by 90% and 70%, respectively. PCB exposure, following DA depletion, neither increased levels of oxidative stress nor resulted in GABA depletion. These results suggest that PCB-induced alterations in the vesicular storage of DA, resulting in increased levels of unsequestered DA, leads to increased oxidative stress, depletion of tissue glutathione, and consequent reductions in tissue GABA concentrations.

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“…Lead induces oxidative stress and increases DNA damage [29] . PCBs induce lipid peroxidation [30] . Urinary porphyrin profiles strongly suggest heavy metal toxicity in autism [31] .…”

Section: Implication Of Environmental Factors In Autismmentioning

confidence: 99%

Oxidative Stress in Autism: Elevated Cerebellar 3-nitrotyrosine Levels

Sajdel-Sulkowska¹,

Lipiński²,

Windom³

et al. 2008

American J. of Biochemistry and Biotechnology

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It has been suggested that oxidative stress and/or mercury compounds play an important role in the pathophysiology of autism. This study compared for the first time the cerebellar levels of the oxidative stress marker 3-nitrotyrosine (3-NT), mercury (Hg) and the antioxidant selenium (Se) levels between control and autistic subjects. Tissue homogenates were prepared in the presence of protease inhibitors from the frozen cerebellar tissue of control (n=10; mean age, 15.5 years; mean PMI, 15.5 hours) and autistic (n=9; mean age 12.1 years; mean PMI, 19.3 hours) subjects. The concentration of cerebellar 3-NT, determined by ELISA, in controls ranged from 13.69 to 49.04 pmol g 1 of tissue; the concentration of 3-NT in autistic cases ranged from 3.91 to 333.03 pmol g 1 of tissue. Mean cerebellar 3-NT was elevated in autism by 68.9% and the increase was statistically significant (p=0.045). Cerebellar Hg, measured by atomic absorption spectrometry ranged from 0.9 to 35 pmol g 1 tissue in controls (n=10) and from 3.2 to 80.7 pmol g 1 tissue in autistic cases (n=9); the 68.2% increase in cerebellar Hg was not statistically significant. However, there was a positive correlation between cerebellar 3-NT and Hg levels (r=0.7961, p=0.0001). A small decrease in cerebellar Se levels in autism, measured by atomic absorption spectroscopy, was not statistically significant but was accompanied by a 42.9% reduction in the molar ratio of Se to Hg in the autistic cerebellum. While preliminary, the results of the present study add elevated oxidative stress markers in brain to the growing body of data reflecting greater oxidative stress in autism.

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Antioxidant effect of ascorbic acid on PCB (Aroclor 1254) induced oxidative stress in hypothalamus of albino rats

Cited by 72 publications

References 44 publications

Effects of polychlorinated biphenyl (Aroclor 1254) on steroidogenesis and antioxidant system in cultured adult rat Leydig cells

Effects of polychlorinated biphenyl (Aroclor 1254) on steroidogenesis and antioxidant system in cultured adult rat Leydig cells

Polychlorinated biphenyl-induced oxidative stress in organotypic co-cultures: Experimental dopamine depletion prevents reductions in GABA

Oxidative Stress in Autism: Elevated Cerebellar 3-nitrotyrosine Levels

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