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J. Arunakaran - One of the best experts on this subject based on the ideXlab platform.
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oxidative stress alters creatine kinase system in serum and brain regions of polychlorinated biphenyl Aroclor 1254 exposed rats protective role of melatonin
Basic & Clinical Pharmacology & Toxicology, 2009Co-Authors: P Venkataraman, Gunasekaran Krishnamoorthy, Kandaswamy Selvakumar, J. ArunakaranAbstract:Abstract: Polychlorinated biphenyls are one of the environmental toxicants and neurotoxic compounds which induce the production of free radicals. Creatine kinase plays a key role in energy metabolism of nervous tissue and might be one of the targets for reactive oxygen species. Melatonin, an indoleamine, plays an important role in neurodegenerative diseases as an antioxidant and neuroprotector. The objective of the present study was to investigate the protective role of melatonin on polychlorinated biphenyl (Aroclor 1254)-induced oxidative stress and the changes in creatine kinase activity in brain regions of adult rats. Group I: rats were intraperitoneally (i.p.) administered with corn oil (vehicle) for 30 days. Group II: rats injected i.p. with Aroclor 1254 at 2 mg/kg body weight (bw)/day for 30 days. Groups III and IV: rats i.p. received melatonin (5 or 10 mg/kg bw/day) simultaneously with Aroclor 1254 for 30 days. After 30 days, rats were killed and the brain regions were dissected to cerebral cortex, cerebellum and hippocampus. Lipid peroxidation, hydroxyl radical and hydrogen peroxide (H2O2) levels were determined. The activity of creatine kinase was assayed in serum and brain regions, and its isoenzymes in serum were separated electrophoretically. Activity of creatine kinase was decreased while an increase in H2O2, hydroxyl radical and lipid peroxidation was observed in brain regions of polychlorinated biphenyl-treated rats. Also polychlorinated biphenyl exposure showed a significant increase in serum creatine kinase level and its isoforms such as BB-creatine kinase, MB-creatine kinase, and MM-creatine kinase. Administration of melatonin prevented these alterations induced by polychlorinated biphenyl by its free radical scavenging mechanism. Thus, polychlorinated biphenyl alters creatine kinase activity by inducing oxidative stress in brain regions, which can be protected by melatonin.
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studies on the protective role of lycopene against polychlorinated biphenyls Aroclor 1254 induced changes in star protein and cytochrome p450 scc enzyme expression on leydig cells of adult rats
Reproductive Toxicology, 2009Co-Authors: Perumal Elumalai, Gunasekaran Krishnamoorthy, P Venkataraman, Kandaswamy Selvakumar, Ramachandran Arunkumar, J. ArunakaranAbstract:Abstract Polychlorinated biphenyls (PCBs) are ubiquitous and persistent environmental contaminants that disturb normal endocrine functions, including gonadal functions in humans and mammals. PCBs (Aroclor 1254) - induced toxic manifestations are associated with the production of free radicals. Lycopene belongs to the group of natural carotenoids, which are found in many fruits, vegetables and other green plants. Lycopene, the most potent antioxidant protects against oxidative damage. The present study was conducted to elucidate the protective role of lycopene against Aroclor 1254-induced changes in Leydig cellular steroidogenic acute regulatory (StAR) protein, cytochrome P450 side chain cleavage (P450 scc) enzyme expression and 3β-hydroxy steroid dehydrogenase (3β-HSD) activity. The rats were divided into four groups. Each group consists of six animals. Group I rats were administered with corn oil intraperitoneally (i.p.) for 30 days. Group II rats were treated with Aroclor 1254 (i.p.) 2 mg kg −1 body weight (bwt) day −1 for 30 days. Group III rats were treated with Aroclor 1254 (i.p.) 2 mg kg −1 bwt day −1 along with simultaneous supplementation of lycopene 4 mg kg −1 bwt day −1 (gavage) for 30 days. Group IV rats administered with lycopene alone at the dose of 4 mg kg −1 bwt day −1 (gavage) for 30 days. After 24 h of the last treatment, animals were decapitated, blood was collected and serum testosterone level was estimated by radioimmunoassay (RIA). Testes were removed and Leydig cells were isolated in aseptic condition. StAR protein, cytochrome P450 scc enzyme expression were studied by Western blot analysis and 3β-HSD activity was estimated spectrophotometrically. Aroclor 1254 treatment significantly reduced the serum testosterone level. Simultaneous supplementation of lycopene maintained the serum testosterone to near normal. Aroclor 1254 exposure decreased Leydig cellular StAR protein, cytochrome P450 scc enzyme expression and activity of 3β-HSD. However, simultaneous supplementation of lycopene improved Leydig cellular StAR protein, cytochrome P450 scc expression and activity of 3β-HSD. These results suggested that lycopene have ameliorative role against Aroclor 1254 induced Leydig cell dysfunction.
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polychlorinated biphenyl Aroclor 1254 inhibits testosterone biosynthesis and antioxidant enzymes in cultured rat leydig cells
Reproductive Toxicology, 2008Co-Authors: Palaniappan Murugesan, K Balasubramanian, Thirupathi Muthusamy, J. ArunakaranAbstract:Polychlorinated biphenyls (PCBs) are environmental contaminants that in humans and animals disturb normal endocrine functions including gonadal functions. The present studies were aimed at determining the direct effects of PCB on Leydig cell testosterone production and antioxidant system in vitro. Adult Leydig cells were purified by Percoll gradient centrifugation method and the purity of Leydig cells was also determined by 3beta-hydroxysteroid dehydrogenase (3beta-HSD) staining method. Purified Leydig cells were exposed to different concentrations (10(-10) to 10(-7) M) of PCB (Aroclor 1254) for 6 and 12 h under basal and LH-stimulated conditions. After incubation, the cultured media were collected and used for the assay of testosterone. The treated cells were used for quantification of cell surface LH receptors and activity of steroidogenic enzymes such as cytochrome P450 side chain cleavage enzyme (P450scc), 3beta-HSD and 17beta-hydroxysteroid dehydrogenase (17beta-HSD). In addition, Leydig cellular enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), gamma-glutamyl transpeptidase (gamma-GT), glutathione-S-transferase (GST) and non-enzymatic antioxidants such as vitamin C and E were assayed. Lipid peroxidation (LPO) and reactive oxygen species (ROS) were also estimated in Leydig cells. The results indicated that Aroclor 1254 (10(-8) and 10(-7) M) treatments significantly inhibit basal and LH-stimulated testosterone production. In addition to this, the activity of steroidogenic enzymes, enzymatic and non-enzymatic antioxidants were significantly diminished in a dose- and time-dependent manner. Moreover, the LPO and ROS were elevated in a dose- and time-dependent manner under basal and LH-stimulated conditions. These findings suggest that PCBs can act directly on Leydig cells to inhibit testosterone biosynthesis by reducing steroidogenic enzymes, enzymatic and non-enzymatic antioxidants.
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effects of Aroclor 1254 on femoral bone metabolism in adult male wistar rats
Toxicology, 2007Co-Authors: Govindan Ramajayam, M A Sridhar, S Karthikeyan, R Lavanya, S Veni, R C Vignesh, R Ilangovan, Sitta S Djody, V Gopalakrishnan, J. ArunakaranAbstract:Environmental pollutants that disrupt endocrine system might also affect the modeling and remodeling of bone. Environmental factors, irrespective of age and sex contribute for the development of secondary osteoporosis. Polychlorinated biphenyls have adverse effects on various organs including bone. The present study was designed to investigate the effects of PCB (Aroclor 1254) on femur bone and the ameliorative role of vitamin C or E. In this regard, four groups of adult male albino rats were used as control, PCB (2 mg/kg b.wt.), PCB + vitamin C (100 mg/kg b.wt.) and PCB + vitamin E (50 mg/kg b.wt.). The bone formation markers (ALP, Collagen), bone resorption marker (TRAP), antioxidant enzymes (SOD, GPX and GST) and lipid peroxidation in the femur were studied. Aroclor 1254 treatment decreased the ALP activity and collagen, but increased the TRAP activity and lipid peroxidation. While it decreased the SOD and GPX activity, GST was unaltered. Interestingly, simultaneous administration of vitamin C or E prevented the adverse effects of Aroclor 1254 in the femur. In conclusion, the present investigation suggests that Aroclor 1254 induced oxidative stress affects femoral bone metabolism. However, vitamin C or vitamin E protected the femur from the oxidative stress.
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oxidative stress modulates membrane bound atpases in brain regions of pcb Aroclor 1254 exposed rats protective role of α tocopherol
Biomedicine & Pharmacotherapy, 2007Co-Authors: N Sridevi, P Venkataraman, Gunasekaran Krishnamoorthy, Kalimuthu Senthilkumar, J. ArunakaranAbstract:Abstract Polychlorinated biphenyls (PCBs) are a class of widely dispersed and environmentally persistent organic compounds. PCBs exhibit a wide range of toxicological effects including neurotoxicity. Vitamin E (α-tocopherol) is an important lipid soluble antioxidant placed in a special region of membranes. Large amounts of energy are required to maintain the signaling activities of the cells in the central nervous system (CNS). Membrane proteins that control ion gradients across organellar and plasma membranes appear to be particularly susceptible to oxidation-induced changes. The aim of this study was to determine the protective role of vitamin E on Aroclor 1254 induced modulation in membrane bound ATPases in brain regions of rats. One group of rats received corn oil as vehicle for 30 days as control. The other group of rats were administered Aroclor 1254 at a dose of 2 mg kg −1 bw day −1 intraperitoneally for 30 days. One group of rats received vitamin E (50 mg kg −1 bw day −1 ) orally simultaneously with Aroclor 1254 for 30 days. After 30 days, the animals were euthanized and the brain was dissected to hypothalamus and hippocampus to determine the following parameters. Hydrogen peroxide (H 2 O 2 ), Lipid peroxidation (LPO) and the activities of Na + K + -ATPase, Ca 2+ -ATPase and Mg 2+ -ATPase were determined. Reduced glutathione (GSH) level was also determined. Activities of all the enzymes were decreased while an increase in H 2 O 2 and LPO were observed in selected brain regions of PCB treated animals. Simultaneous vitamin E treatment in PCB exposed animals restored all the parameters significantly. These results suggest that oxidative stress is involved in the inhibitory effect of PCB (Aroclor 1254) on membrane bound ATPases in selected brain regions. α-tocopherol acts against PCB induced neurotoxicity by decreasing oxidative stress.
Drew Fackett - One of the best experts on this subject based on the ideXlab platform.
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a comparison of Aroclor 1254 induced and uninduced rat liver microsomes to human liver microsomes in phenytoin o deethylation coumarin 7 hydroxylation tolbutamide 4 hydroxylation s mephenytoin 4 hydroxylation chloroxazone 6 hydroxylation and testoste
Chemico-Biological Interactions, 2001Co-Authors: Judy Easterbrook, Drew Fackett, Albert P LiAbstract:Abstract Aroclor 1254-induced rat liver homogenate supernatant (liver S-9) is routinely used as an exogenous metabolic activation system for the evaluation of mutagenicity of xenobiotics. The purpose of this study is to evaluate whether results obtained with Aroclor 1254-induced liver microsomes would be relevant to human. Aroclor 1254-induced and uninduced rat liver microsomes were compared to human liver microsomes in the metabolism of substrates which are known to be selectively metabolized by the major human cytochrome P450 (CYP) isoforms. The activities studied and the major CYP isoforms involved were as follows: phenacetin O -deethylation (CYP1A2); coumarin 7-hydroxylation, (CYP2A6); tolbutamide 4-hydroxylation (CYP2C9), S- mephenytoin 4′-hydroxylation (CYP2C19); dextromethorphan O -demethylation (CYP2D6); chloroxazone 6-hydroxylation (CYP2E1); and testosterone 6β-hydroxylation (CYP3A4). We found that both induced and uninduced rat liver microsomes were active in all the pathways studied with the exception of coumarin 7-hydroxylation. Coumarin 7-hydroxylation was observed with human liver microsomes but not the rat liver microsomes. Aroclor-1254 was found to induce all activities measured, with the exception of coumarin 7-hydroxylation. Dextromethorphan O -deethylation activity was higher in the rat liver microsomes than the human liver microsomes. Testosterone 6β-hydroxylation activity was found to be similar between the human liver microsomes and the induced rat liver microsomes. Our results suggest that experimental data obtained with Aroclor 1254-induced rat liver microsomes may not always be relevant to human.
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a comparison of Aroclor 1254 induced and uninduced rat liver microsomes to human liver microsomes in phenytoin o deethylation coumarin 7 hydroxylation tolbutamide 4 hydroxylation s mephenytoin 4 hydroxylation chloroxazone 6 hydroxylation and testoste
Chemico-Biological Interactions, 2001Co-Authors: Judy Easterbrook, Drew FackettAbstract:Aroclor 1254-induced rat liver homogenate supernatant (liver S-9) is routinely used as an exogenous metabolic activation system for the evaluation of mutagenicity of xenobiotics. The purpose of this study is to evaluate whether results obtained with Aroclor 1254-induced liver microsomes would be relevant to human. Aroclor 1254-induced and uninduced rat liver microsomes were compared to human liver microsomes in the metabolism of substrates which are known to be selectively metabolized by the major human cytochrome P450 (CYP) isoforms. The activities studied and the major CYP isoforms involved were as follows: phenacetin O-deethylation (CYP1A2); coumarin 7-hydroxylation, (CYP2A6); tolbutamide 4-hydroxylation (CYP2C9), S-mephenytoin 4'-hydroxylation (CYP2C19); dextromethorphan O-demethylation (CYP2D6); chloroxazone 6-hydroxylation (CYP2E1); and testosterone 6beta-hydroxylation (CYP3A4). We found that both induced and uninduced rat liver microsomes were active in all the pathways studied with the exception of coumarin 7-hydroxylation. Coumarin 7-hydroxylation was observed with human liver microsomes but not the rat liver microsomes. Aroclor-1254 was found to induce all activities measured, with the exception of coumarin 7-hydroxylation. Dextromethorphan O-deethylation activity was higher in the rat liver microsomes than the human liver microsomes. Testosterone 6beta-hydroxylation activity was found to be similar between the human liver microsomes and the induced rat liver microsomes. Our results suggest that experimental data obtained with Aroclor 1254-induced rat liver microsomes may not always be relevant to human.
Judy Easterbrook - One of the best experts on this subject based on the ideXlab platform.
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a comparison of Aroclor 1254 induced and uninduced rat liver microsomes to human liver microsomes in phenytoin o deethylation coumarin 7 hydroxylation tolbutamide 4 hydroxylation s mephenytoin 4 hydroxylation chloroxazone 6 hydroxylation and testoste
Chemico-Biological Interactions, 2001Co-Authors: Judy Easterbrook, Drew Fackett, Albert P LiAbstract:Abstract Aroclor 1254-induced rat liver homogenate supernatant (liver S-9) is routinely used as an exogenous metabolic activation system for the evaluation of mutagenicity of xenobiotics. The purpose of this study is to evaluate whether results obtained with Aroclor 1254-induced liver microsomes would be relevant to human. Aroclor 1254-induced and uninduced rat liver microsomes were compared to human liver microsomes in the metabolism of substrates which are known to be selectively metabolized by the major human cytochrome P450 (CYP) isoforms. The activities studied and the major CYP isoforms involved were as follows: phenacetin O -deethylation (CYP1A2); coumarin 7-hydroxylation, (CYP2A6); tolbutamide 4-hydroxylation (CYP2C9), S- mephenytoin 4′-hydroxylation (CYP2C19); dextromethorphan O -demethylation (CYP2D6); chloroxazone 6-hydroxylation (CYP2E1); and testosterone 6β-hydroxylation (CYP3A4). We found that both induced and uninduced rat liver microsomes were active in all the pathways studied with the exception of coumarin 7-hydroxylation. Coumarin 7-hydroxylation was observed with human liver microsomes but not the rat liver microsomes. Aroclor-1254 was found to induce all activities measured, with the exception of coumarin 7-hydroxylation. Dextromethorphan O -deethylation activity was higher in the rat liver microsomes than the human liver microsomes. Testosterone 6β-hydroxylation activity was found to be similar between the human liver microsomes and the induced rat liver microsomes. Our results suggest that experimental data obtained with Aroclor 1254-induced rat liver microsomes may not always be relevant to human.
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a comparison of Aroclor 1254 induced and uninduced rat liver microsomes to human liver microsomes in phenytoin o deethylation coumarin 7 hydroxylation tolbutamide 4 hydroxylation s mephenytoin 4 hydroxylation chloroxazone 6 hydroxylation and testoste
Chemico-Biological Interactions, 2001Co-Authors: Judy Easterbrook, Drew FackettAbstract:Aroclor 1254-induced rat liver homogenate supernatant (liver S-9) is routinely used as an exogenous metabolic activation system for the evaluation of mutagenicity of xenobiotics. The purpose of this study is to evaluate whether results obtained with Aroclor 1254-induced liver microsomes would be relevant to human. Aroclor 1254-induced and uninduced rat liver microsomes were compared to human liver microsomes in the metabolism of substrates which are known to be selectively metabolized by the major human cytochrome P450 (CYP) isoforms. The activities studied and the major CYP isoforms involved were as follows: phenacetin O-deethylation (CYP1A2); coumarin 7-hydroxylation, (CYP2A6); tolbutamide 4-hydroxylation (CYP2C9), S-mephenytoin 4'-hydroxylation (CYP2C19); dextromethorphan O-demethylation (CYP2D6); chloroxazone 6-hydroxylation (CYP2E1); and testosterone 6beta-hydroxylation (CYP3A4). We found that both induced and uninduced rat liver microsomes were active in all the pathways studied with the exception of coumarin 7-hydroxylation. Coumarin 7-hydroxylation was observed with human liver microsomes but not the rat liver microsomes. Aroclor-1254 was found to induce all activities measured, with the exception of coumarin 7-hydroxylation. Dextromethorphan O-deethylation activity was higher in the rat liver microsomes than the human liver microsomes. Testosterone 6beta-hydroxylation activity was found to be similar between the human liver microsomes and the induced rat liver microsomes. Our results suggest that experimental data obtained with Aroclor 1254-induced rat liver microsomes may not always be relevant to human.
Albert P Li - One of the best experts on this subject based on the ideXlab platform.
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a comparison of Aroclor 1254 induced and uninduced rat liver microsomes to human liver microsomes in phenytoin o deethylation coumarin 7 hydroxylation tolbutamide 4 hydroxylation s mephenytoin 4 hydroxylation chloroxazone 6 hydroxylation and testoste
Chemico-Biological Interactions, 2001Co-Authors: Judy Easterbrook, Drew Fackett, Albert P LiAbstract:Abstract Aroclor 1254-induced rat liver homogenate supernatant (liver S-9) is routinely used as an exogenous metabolic activation system for the evaluation of mutagenicity of xenobiotics. The purpose of this study is to evaluate whether results obtained with Aroclor 1254-induced liver microsomes would be relevant to human. Aroclor 1254-induced and uninduced rat liver microsomes were compared to human liver microsomes in the metabolism of substrates which are known to be selectively metabolized by the major human cytochrome P450 (CYP) isoforms. The activities studied and the major CYP isoforms involved were as follows: phenacetin O -deethylation (CYP1A2); coumarin 7-hydroxylation, (CYP2A6); tolbutamide 4-hydroxylation (CYP2C9), S- mephenytoin 4′-hydroxylation (CYP2C19); dextromethorphan O -demethylation (CYP2D6); chloroxazone 6-hydroxylation (CYP2E1); and testosterone 6β-hydroxylation (CYP3A4). We found that both induced and uninduced rat liver microsomes were active in all the pathways studied with the exception of coumarin 7-hydroxylation. Coumarin 7-hydroxylation was observed with human liver microsomes but not the rat liver microsomes. Aroclor-1254 was found to induce all activities measured, with the exception of coumarin 7-hydroxylation. Dextromethorphan O -deethylation activity was higher in the rat liver microsomes than the human liver microsomes. Testosterone 6β-hydroxylation activity was found to be similar between the human liver microsomes and the induced rat liver microsomes. Our results suggest that experimental data obtained with Aroclor 1254-induced rat liver microsomes may not always be relevant to human.
Palaniappan Murugesan - One of the best experts on this subject based on the ideXlab platform.
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polychlorinated biphenyl Aroclor 1254 inhibits testosterone biosynthesis and antioxidant enzymes in cultured rat leydig cells
Reproductive Toxicology, 2008Co-Authors: Palaniappan Murugesan, K Balasubramanian, Thirupathi Muthusamy, J. ArunakaranAbstract:Polychlorinated biphenyls (PCBs) are environmental contaminants that in humans and animals disturb normal endocrine functions including gonadal functions. The present studies were aimed at determining the direct effects of PCB on Leydig cell testosterone production and antioxidant system in vitro. Adult Leydig cells were purified by Percoll gradient centrifugation method and the purity of Leydig cells was also determined by 3beta-hydroxysteroid dehydrogenase (3beta-HSD) staining method. Purified Leydig cells were exposed to different concentrations (10(-10) to 10(-7) M) of PCB (Aroclor 1254) for 6 and 12 h under basal and LH-stimulated conditions. After incubation, the cultured media were collected and used for the assay of testosterone. The treated cells were used for quantification of cell surface LH receptors and activity of steroidogenic enzymes such as cytochrome P450 side chain cleavage enzyme (P450scc), 3beta-HSD and 17beta-hydroxysteroid dehydrogenase (17beta-HSD). In addition, Leydig cellular enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), gamma-glutamyl transpeptidase (gamma-GT), glutathione-S-transferase (GST) and non-enzymatic antioxidants such as vitamin C and E were assayed. Lipid peroxidation (LPO) and reactive oxygen species (ROS) were also estimated in Leydig cells. The results indicated that Aroclor 1254 (10(-8) and 10(-7) M) treatments significantly inhibit basal and LH-stimulated testosterone production. In addition to this, the activity of steroidogenic enzymes, enzymatic and non-enzymatic antioxidants were significantly diminished in a dose- and time-dependent manner. Moreover, the LPO and ROS were elevated in a dose- and time-dependent manner under basal and LH-stimulated conditions. These findings suggest that PCBs can act directly on Leydig cells to inhibit testosterone biosynthesis by reducing steroidogenic enzymes, enzymatic and non-enzymatic antioxidants.
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effects of vitamins c and e on steroidogenic enzymes mrna expression in polychlorinated biphenyl Aroclor 1254 exposed adult rat leydig cells
Toxicology, 2007Co-Authors: Palaniappan Murugesan, K Balasubramanian, Thirupathi Muthusamy, J. ArunakaranAbstract:Polychlorinated biphenyls (PCBs) are ubiquitous and persistent environmental contaminants that disturb normal endocrine functions including gonadal functions in humans and mammals. The present study was conducted to elucidate the protective role of vitamins C and E against Aroclor 1254-induced changes in Leydig cell steroidogenic acute regulatory (StAR) protein and steroidogenic enzymes mRNA expression. Adult male rats were dosed for 30 days with daily intraperitoneal (i.p.) injection of 2 mg/kg Aroclor 1254 or vehicle (corn oil). One group of rats was treated with vitamin C (100 mg/kg bw day) while the other group was treated with vitamin E (50 mg/kg bw day) orally, simultaneously with Aroclor 1254 for 30 days. One day after the last treatment, animals were euthanized and blood was collected for the assay of serum hormones such as luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol. The serum androgen binding protein was also estimated. Testes were quickly removed and Leydig cells were isolated in aseptic condition. Purity of Leydig cells was determined by 3beta-hydroxysteroid dehydrogenase (3beta-HSD) staining methods. Purified Leydig cells were used for quantification of androgen and estrogen receptors. In addition, total RNA was isolated from control and treated Leydig cells to monitor the steady-state mRNA levels by RT-PCR for StAR protein, cytochrome P(450)scc, 3beta-HSD and 17beta-HSD. Aroclor 1254 treatment significantly reduced the serum LH, FSH, testosterone, estradiol and androgen binding protein. In addition to this, Leydig cell androgen and estrogen receptors were markedly decreased. RT-PCR analysis of StAR mRNA level did not alter Aroclor 1254 treatment while steroidogenic enzymes such as cytochrome P(450)scc, 3beta-HSD and 17beta-HSD mRNAs were drastically decreased in Aroclor 1254 treatment. However, the simultaneous administration of vitamins C or E in Aroclor 1254-exposed rats resulted a significant restoration of all the above-mentioned parameters to the control level. These observations suggest that vitamins C and E have ameliorative role against PCBs-induced testicular Leydig cells dysfunction.
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effects of polychlorinated biphenyl Aroclor 1254 on steroidogenesis and antioxidant system in cultured adult rat leydig cells
Journal of Endocrinology, 2007Co-Authors: Palaniappan Murugesan, K Balasubramanian, Muthusamy Balaganesh, J. ArunakaranAbstract: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 3beta-hydroxysteroid dehydrogenase (3beta-HSD) staining method. Purified Leydig cells were exposed to different concentrations (10(- 10)-10(- 7) 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 (P450scc), 3beta-HSD, and 17beta-hydroxysteroid dehydrogenase (17beta-HSD). Leydig cellular enzymatic antioxidants, such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, gamma-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 acute-regulatory (StAR) protein, cytochrome P450scc, 3beta-HSD, and 17beta-HSD. Our results indicated that Aroclor 1254 (10(- 9), 10(- 8), and 10(- 7) 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(- 7) M dose of Aroclor 1254 treatment, while cytochrome P(450)scc, 3beta-HSD, and 17beta-HSD mRNAs were drastically decreased in both 10(- 8) and 10(- 7) 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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studies on the protective role of vitamin c and e against polychlorinated biphenyl Aroclor 1254 induced oxidative damage in leydig cells
Free Radical Research, 2005Co-Authors: Palaniappan Murugesan, K Balasubramanian, Thirupathi Muthusamy, J. ArunakaranAbstract:Free radical production and lipid peroxidation are potentially important mediators in testicular physiology and toxicology. Polychlorinated biphenyls (PCBs) are global environmental contaminants that cause disruption of the endocrine system in human and animals. The present study was conducted to elucidate the protective role of vitamin C and E against Aroclor 1254-induced changes in Leydig cell steroidogenesis and antioxidant system. Adult male rats were dosed for 30 days with daily intraperitoneal (ip) injection of 2 mg/kg Aroclor or vehicle (corn oil). One group of rats was treated with vitamin C (100 mg/kg bw/day) while the other group was treated with vitamin E (50 mg/kg bw/day) orally, simultaneously with Aroclor 1254 for 30 days. One day after the last treatment, animals were euthanized and blood was collected for the assay of serum hormones such as luteinizing hormone (LH), thyroid stimulating hormone (TSH), prolactin (PRL), triiodothyronine (T3), thyroxine (T4), testosterone and estradiol. Testes...
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effect of Aroclor 1254 on sertoli cellular antioxidant system androgen binding protein and lactate in adult rat in vitro
Toxicology, 2005Co-Authors: Gunasekaran Krishnamoorthy, Palaniappan Murugesan, M M Aruldhas, R Muthuvel, D N Gunadharini, M R Vijayababu, A Arunkumar, P Venkataraman, J. ArunakaranAbstract:Abstract Polychlorinated biphenyls (PCBs) are persistent and bioaccumulative environmental toxicants. Previous studies suggested that PCBs (Aroclor 1254) induce toxic effects including reproductive toxicity. The present study was designed to investigate the impact of Aroclor 1254 on Sertoli cellular function and antioxidant system of adult rat in vitro. Sertoli cells were isolated from adult rat testes and treated with various concentrations (10 −10 to 10 −7 M) of Aroclor 1254 for 6, 12 and 24 h. After the treatment period, cell viability was assessed and the Sertoli cellular antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), γ-glutamyl transpeptidase (γ-GT) and glutathione reductase (GR) and lipid peroxidation (LPO) were assayed. In addition, androgen binding protein (ABP) and lactate secretions were also quantified in Sertoli cell culture medium. Sertoli cellular viability and activity of antioxidant enzymes were significantly reduced in Aroclor 1254 (10 −10 to 10 −7 M) treatment for 6, 12 and 24 h whereas, the Sertoli cellular lipid peroxidation was significantly increased in a dose and duration dependent manner. In addition, ABP secretion diminished and lactate secretion was significantly elevated in the same manner. To conclude, the present study suggested that Aroclor 1254 disrupts Sertoli cellular metabolic functions such as ABP, lactate secretions and activity of antioxidant enzymes.