1-Bromopropane

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Gaku Ichihara - One of the best experts on this subject based on the ideXlab platform.

  • Role of cytochrome P450s in the male reproductive toxicity of 1-Bromopropane.
    Toxicology research, 2016
    Co-Authors: Cai Zong, C. Edwin Garner, Chinyen Huang, Xiao Zhang, Jie Chang, Masashi Kato, Toshihiro Sakurai, Sahoko Ichihara, Gaku Ichihara
    Abstract:

    1-Bromopropane (1BP) is widely used as an alternative to ozone-depleting solvents. The present study investigated the role of P450s in 1BP-induced male reproductive toxicity. Mice co-treated with 1-aminobenzotriazole (ABT), a non-selective P450 inhibitor, were exposed to 1BP at 0, 50, 250, or 1200 ppm, while saline-treated control mice were exposed to 1BP at 0, 50, or 250 ppm, for 4 weeks. In the saline-treated mice, exposure to 1BP at 250 ppm decreased the sperm count and sperm motility. Histopathological examination showed that exposure to 1BP at 50 and 250 ppm increased the number of elongated spermatids retained at the basal region of stage IX, X and XI seminiferous tubules, while exposure to 1BP at 250 ppm increased the number of periodic acid-Schiff (PAS)-positive round structures in stage IX, X, and XI seminiferous tubules. Co-treatment with ABT prevented the above changes induced by exposure to 1BP at 50 or 250 ppm. However, ABT-treated mice exposed to 1BP in the 1200 ppm group showed decreases in the weights of reproductive organs, epididymal sperm count and motility, increases in epididymal sperm with abnormal heads, retained spermatids and PAS-positive round structures in stages IX–XI, depletion of spermatogenic cells in part of the seminiferous tubules, and a small number of round spermatids in stage VII seminiferous tubules. The results at 50 and 250 ppm of 1-BP exposure indicate that P450s play important roles in 1BP-induced testicular toxicity. The control of P450 activity reduced 1BP-induced male reproductive toxicities including spermiation failure, reduction of epididymal sperm count and motility, and formation of PAS-positive round structures at postspermiation stages.

  • Hippocampal phosphoproteomics of F344 rats exposed to 1-Bromopropane.
    Toxicology and applied pharmacology, 2014
    Co-Authors: Zhenlie Huang, Lingyi Zhang, Jie Chang, Sahoko Ichihara, Shinji Oikawa, Hanlin Huang, Gaku Ichihara
    Abstract:

    1-Bromopropane (1-BP) is neurotoxic in both experimental animals and human. To identify phosphorylated modification on the unrecognized post-translational modifications of proteins and investigate their role in 1-BP-induced neurotoxicity, changes in hippocampal phosphoprotein expression levels were analyzed quantitatively in male F344 rats exposed to 1-BP inhalation at 0, 400, or 1000 ppm for 8 h/day for 1 or 4 weeks. Hippocampal protein extracts were analyzed qualitatively and quantitatively by Pro-Q Diamond gel staining and SYPRO Ruby staining coupled with two-dimensional difference in gel electrophoresis (2D-DIGE), respectively, as well as by matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) to identify phosphoproteins. Changes in selected proteins were further confirmed by Manganese II (Mn2 +)-Phos-tag SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Bax and cytochrome c protein levels were determined by western blotting. Pro-Q Diamond gel staining combined with 2D-DIGE identified 26 phosphoprotein spots (p < 0.05), and MALDI-TOF/MS identified 18 up-regulated proteins and 8 down-regulated proteins. These proteins are involved in the biological process of response to stimuli, metabolic processes, and apoptosis signaling. Changes in the expression of phosphorylated 14-3-3 θ were further confirmed by Mn2 +-Phos-tag SDS-PAGE. Western blotting showed overexpression of Bax protein in the mitochondria with down-regulation in the cytoplasm, whereas cytochrome c expression was high in the cytoplasm but low in the mitochondria after 1-BP exposure. Our results suggest that the pathogenesis of 1-BP-induced hippocampal damage involves inhibition of antiapoptosis process. Phosphoproteins identified in this study can potentially serve as biomarkers for 1-BP-induced neurotoxicity.

  • Effects of sub-acute and sub-chronic inhalation of 1-Bromopropane on neurogenesis in adult rats.
    Toxicology, 2012
    Co-Authors: Lingyi Zhang, Sahoko Ichihara, Taku Nagai, Kiyofumi Yamada, Daisuke Ibi, Kaviarasan Subramanian, Zhenlie Huang, Sahabudeen Sheik Mohideen, Hisao Naito, Gaku Ichihara
    Abstract:

    a b s t r a c t Purpose: 1-Bromopropane (1-BP) intoxication is associated with depression and cognitive and memory deficits. The present study tested the hypothesis that 1-BP suppresses neurogenesis in the dentate gyrus, which is involved in higher cerebral function, in adult rats.

  • A Case of Severe Neurotoxicity Associated With Exposure to 1-Bromopropane, an Alternative to Ozone-Depleting or Global-Warming Solvents
    Archives of internal medicine, 2012
    Co-Authors: Makoto Samukawa, Gaku Ichihara, Nobuyuki Oka, Susumu Kusunoki
    Abstract:

    Health hazard alerts to 1-Bromopropane, an alternative to ozone layer–damaging organic solvents, have been issued by some countries. Herein, we report a new case of 1-Bromopropane–induced neurotoxicity. A 43-year-old male industrial worker developed muscle weakness, pain, numbness, and gait disturbance. Neurological examination indicated sensory ataxic neuropathy associated with mild impairment of upper motor neurons. He had used 1-Bromopropane as a cleaning agent for metal parts at his workplace without appropriate protection. The serum bromide level was elevated at the onset of clinical manifestations. Histopathologic examination of sural nerve biopsy showed axonal damage. Under the tentative diagnosis of 1-Bromopropane toxicity, he was kept away from exposure to the solvent. This resulted in gradual improvement of symptoms, recovery of motor function, and resolution of sensory deficits. The diagnosis of 1-Bromopropane neurotoxicity in this case was based on details of the work environment, the clinical course, and laboratory and pathologic findings. To our knowledge, this is the first report that describes nerve biopsy findings in a human case.

  • Neurotoxicity of 1-Bromopropane: Evidence from animal experiments and human studies
    Journal of Advanced Research, 2012
    Co-Authors: Gaku Ichihara, Xuncheng Ding, Junzoh Kitoh, Sahoko Ichihara, Yasuhiro Takeuchi
    Abstract:

    Abstract 1-Bromopropane was introduced as an alternative to ozone layer-depleting solvents such as chlorofluorocarbons and 1,1,1-trichloroethane. However, a dozen human cases have been reported with symptoms and signs of toxicity to 1-Bromopropane including numbness, diminished vibration sense in the lower extremities as well as ataxic gait. An epidemiological study also demonstrated dose-dependent prolongation of distal latency and decrease in vibration sense in the lower extremities. The initial animal experiments helped to identify and analyze the initial human case of 1-Bromopropane toxicity. However, animal data that can explain the central nervous system disorders in humans are limited. Nonetheless, animal data should be carefully interpreted especially in a high-order function of the central nervous system or neurological signs such as ataxia that is influenced by fundamental anatomical/physiological differences between humans and animals. Enzymatic activity in the liver may explain partly the difference in the susceptibility between humans and animals, but further studies are needed to clarify the biological factors that can explain the difference and commonality among the species.

Tae Cheon Jeong - One of the best experts on this subject based on the ideXlab platform.

  • Identification of a N 7 -guanine adduct of 1-Bromopropane in calf thymus DNA by mass spectrometry
    Molecular & Cellular Toxicology, 2016
    Co-Authors: Pritam Thapa, Mahesh Raj Nepal, Ki Sun Jeong, Mi Jeong Kang, Hye Gwang Jeong, Eun-kyung Kim, Keumhan Noh, Sangkyu Lee, Jun-ho Lee, Tae Cheon Jeong
    Abstract:

    As a replacement for chlorofluorocarbons that cause ozone depletion, 1-Bromopropane has been widely used in work place. In the present study, the formation of N 7-guanine adduct in DNA by 1-Bromopropane was evaluated in vitro to elucidate the possible mechanism of its toxic action. N 7-Propyl guanine was chemically synthesized and structurally characterized by NMR, UV, HPLC, and liquid chromatographyelectrospray ionization mass spectrometry (LC- ESI MS) for using as a reference standard. An incubation of 2ʹ-deoxyguanosine with 1-Bromopropane produced N 7-propyl adduct, which was identified by UV, HPLC and ESI-MS. In addition, N7-guanine adduct was also identified from the incorporation of calf thymus DNA with 1-Bromopropane at the physiological condition by LC-ESI MS. Furthermore, the production of adduct was proportional to the amounts of 1-Bromopropane used. These results indicated that the molecular mechanism underlying toxic effects of 1-Bromopropane would be associated with the adduct formation on DNA at least in part.

  • Identification of a N ^7-guanine adduct of 1-Bromopropane in calf thymus DNA by mass spectrometry
    Molecular & Cellular Toxicology, 2016
    Co-Authors: Pritam Thapa, Mahesh Raj Nepal, Ki Sun Jeong, Mi Jeong Kang, Hye Gwang Jeong, Tae Cheon Jeong
    Abstract:

    As a replacement for chlorofluorocarbons that cause ozone depletion, 1-Bromopropane has been widely used in work place. In the present study, the formation of N ^7-guanine adduct in DNA by 1-Bromopropane was evaluated in vitro to elucidate the possible mechanism of its toxic action. N ^7-Propyl guanine was chemically synthesized and structurally characterized by NMR, UV, HPLC, and liquid chromatographyelectrospray ionization mass spectrometry (LC- ESI MS) for using as a reference standard. An incubation of 2ʹ-deoxyguanosine with 1-Bromopropane produced N ^7-propyl adduct, which was identified by UV, HPLC and ESI-MS. In addition, N7-guanine adduct was also identified from the incorporation of calf thymus DNA with 1-Bromopropane at the physiological condition by LC-ESI MS. Furthermore, the production of adduct was proportional to the amounts of 1-Bromopropane used. These results indicated that the molecular mechanism underlying toxic effects of 1-Bromopropane would be associated with the adduct formation on DNA at least in part.

  • Role of metabolism in 1-Bromopropane-induced hepatotoxicity in mice.
    Journal of toxicology and environmental health. Part A, 2010
    Co-Authors: Sangkyu Lee, Mi Jeong Kang, Hye Gwang Jeong, Tae Won Jeon, Jin Woo Yoo, Wonku Kang, Won Seok Lyoo, Tae Cheon Jeong
    Abstract:

    A possible role of metabolism in 1-Bromopropane (1-BP)-induced hepatotoxicity was investigated in male ICR mice. The depletion of glutathione (GSH) by formation of GSH conjugates was associated with increased hepatotoxicity in 1-BP-treated mice. The formation of S-propyl and 2-hydroxypropyl GSH conjugates were identified in the liver following 1-BP treatment. In addition, the formation of reactive metabolites of 1-BP by certain cytochrome P-450 (CYP) may be involved in 1-BP-induced hepatotoxicity. The decreased content of hepatic GSH produced by 1-BP was associated not only with increased activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) but also with elevated levels of hepatic thiobarbituric acid-reactive substance (TBARS) in mice where metabolic enzymes were induced by pretreatment with phenobarbital. In addition, the hepatotoxicity induced by 1-BP was prevented by pretreatment with SKF-525A. Taken together, the formation of reactive metabolites by CYP and depletion of GS...

  • Role of glutathione conjugation in the hepatotoxicity and immunotoxicity induced by 1-Bromopropane in female BALB/c mice.
    Journal of applied toxicology : JAT, 2007
    Co-Authors: Sangkyu Lee, Hye Gwang Jeong, Eung-seok Lee, Tae Won Jeon, Yong Beom Kim, Tae Cheon Jeong
    Abstract:

    1-Bromopropane (1-BP) is used as a cleaning agent or adhesive solvent in the workplace. In the present study, the hepatotoxic and immunotoxic effects of 1-Bromopropane and its conjugation with glutathione (GSH) were investigated in female BALB/c mice. The animals were treated orally with 200, 500 and 1000 mg kg−1 of 1-BP in corn oil for a dose response study or treated orally with 1000 mg kg−1 of 1-BP for 6, 12, 24 and 48 h for a time course study. The hepatic and splenic contents of GSH were significantly decreased by 1-BP in a dose-dependent manner. S-propyl GSH was identified in livers following treatment with 1-BP by liquid chromatography-electrospray ionization tandem mass spectrometry. When the production of conjugates from 1-BP was investigated in livers following oral treatment with 1000 mg kg−1 of 1-BP for 6, 12, 24 and 48 h, the GSH conjugates were detected maximally 6 h after treatment. Treatment of mice with 1-BP increased the serum activity of alanine aminotransferase dose-dependently. The oral 1-BP treatment significantly suppressed the antibody response to a T-dependent antigen and the production of splenic intracellular IL-2 in response to Con A in a dose-dependent manner. The present results suggested that 1-BP could cause hepatotoxicity and immunotoxicity as well as depletion of GSH content due to the formation of GSH conjugates with 1-BP in female BALB/c mice. Copyright © 2007 John Wiley & Sons, Ltd.

  • Synthesis, characterization andIn vitro identification ofN ^7-Guanine adduct of 2-bromopropane
    Archives of Pharmacal Research, 2002
    Co-Authors: Long-xuan Zhao, Tae Cheon Jeong, Eun-kyung Kim, Hyun-tae Lim, Yoon-soo Moon, Nam-hee Kim, Tae-hyung Kim, Heesung Choi, Whigun Chae, Eung-seok Lee
    Abstract:

    Recently, we have reported that 2-bromopropane might have an immunotoxic potential in rats when exposed for 28 days. In the present studies, the possibility of 2í-deoxyguanosine adduct formation by 2-bromopropane was investigated in vitro to elucidate molecular mechanism of 2-bromopropane-induced immunosuppression. N7 -Guanine adduct of 2′-bromopropane (i.e., N7- isopropyl guanine) was chemically synthesized and structurally characterized by analysis of UV,^1H-NMR,^13C-NMR, COSY and fast atom bombardment mass spectrometry to use as a reference material. Incubation of 2′-deoxyguanosine with an excess amount of 2-bromopropane in PBS buffer solution, pH 7.4, at 37°C for 16 h, followed by a thermal hydrolysis, produced a detectable amount of N7 -isopropyl guanine by an HPLC and UV analysis. The present results suggest that 2-bromopropane might form a DNA adduct in N7 position of 2′-deoxyguanosine at a physiological condition.

Jaime Wisniak - One of the best experts on this subject based on the ideXlab platform.

Yasuhiro Takeuchi - One of the best experts on this subject based on the ideXlab platform.

  • Neurotoxicity of 1-Bromopropane: Evidence from animal experiments and human studies
    Journal of Advanced Research, 2012
    Co-Authors: Gaku Ichihara, Xuncheng Ding, Junzoh Kitoh, Sahoko Ichihara, Yasuhiro Takeuchi
    Abstract:

    Abstract 1-Bromopropane was introduced as an alternative to ozone layer-depleting solvents such as chlorofluorocarbons and 1,1,1-trichloroethane. However, a dozen human cases have been reported with symptoms and signs of toxicity to 1-Bromopropane including numbness, diminished vibration sense in the lower extremities as well as ataxic gait. An epidemiological study also demonstrated dose-dependent prolongation of distal latency and decrease in vibration sense in the lower extremities. The initial animal experiments helped to identify and analyze the initial human case of 1-Bromopropane toxicity. However, animal data that can explain the central nervous system disorders in humans are limited. Nonetheless, animal data should be carefully interpreted especially in a high-order function of the central nervous system or neurological signs such as ataxia that is influenced by fundamental anatomical/physiological differences between humans and animals. Enzymatic activity in the liver may explain partly the difference in the susceptibility between humans and animals, but further studies are needed to clarify the biological factors that can explain the difference and commonality among the species.

  • Dose-dependent neurologic abnormalities in workers exposed to 1-Bromopropane.
    Journal of occupational and environmental medicine, 2010
    Co-Authors: Eiji Shibata, Lingyi Zhang, Hailan Wang, Sahoko Ichihara, Zhijun Zhou, Qiangyi Wang, Kenji Wakai, Yasuhiro Takeuchi
    Abstract:

    Objectives:To investigate the health effects of 1-Bromopropane (1-BP) and its dose-dependency in 1-BP production factories in China.Methods:Data of 60 female and 26 male workers in three 1-BP factories and the same number of age-, sex-, and region-matched controls were interviewed and examined. The

  • Exposure to 1-Bromopropane causes dose-dependent neurological abnormalities in workers
    Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational di, 2010
    Co-Authors: Qiangyi Wang, Gaku Ichihara, Xuncheng Ding, Yasuhiro Takeuchi, Zhijun Zhou
    Abstract:

    Objective To explore the dose-effect relationship between 1-Bromopropane (1-BP) exposure and health effects in workers. Methods Occupational field investigations were conducted in 1-BP factories. Ambient 1-BP concentrations were detected with detection tube, and the 8 h time-weighted average individual exposure levels (TWA-8 h) were measured by passive sampler. Workers underwent questionnaire survey, neurological examination, nerve conduction velocity examination, vibration sensation test, routine blood test as well as blood biochemical test. According to TWA values or TWA × duration values, workers were divided into three dose groups for dose-effect relationship analysis. USEPA BMDS 2.1 software was applied to calculate 1-BP benchmark dose (BMD) and its 95% lower limit (BMDL). Results The TWA-8h concentrations ranged from 0.35 to 535.19 mg/m3 (geo-mean 14.08 mg/m3). Dose-dependent analysis showed that the motor nerve distal latency (linear regression coefficient was 0.066 6), vibration sensation of toes (linear regression coefficient were 0.157 2 and 0.193 9), creatine kinase (linear regression coefficient was-1.05) and thyroid stimulating hormone levels (linear regression coefficient was 0.102 4) of 1-BP exposed workers changed in a dose-dependent manner (P

  • Dose-dependent biochemical changes in rat central nervous system after 12-week exposure to 1-Bromopropane.
    Neurotoxicology, 2003
    Co-Authors: Hailan Wang, Hidenori Ito, Gaku Ichihara, Tetsuya Yamada, Kanefusa Kato, Junzoh Kitoh, Seiji Tsuboi, Yoshinori Moriyama, Yasuhiro Takeuchi
    Abstract:

    Abstract 1-Bromopropane is used as a cleaning agent or adhesive solvent in the workplace. The present study investigated the long-term effects of exposure to 1-Bromopropane on biochemical components in the central nervous system (CNS) of rats. Four groups, each of nine male Wistar rats, were exposed to 200, 400, or 800 ppm 1-Bromopropane or fresh air only, 8 h per day, 7 days a week for 12 weeks. We measured the levels of neuron-specific γ-enolase, glia-specific β-S100 protein, creatine kinase (CK) subunits B and M, heat shock protein Hsp27 (by enzyme immunoassay), enzymatic activity of CK and levels of glutathione (GSH), oxidized glutathione (GSSG) and sulfhydrul (SH) base in the cerebrum, cerebellum, brainstem and spinal cord. γ-Enolase decreased dose-dependently in the cerebrum, which showed a decrease in wet weight, at 400 ppm or over, but no change was noted in β-S100 protein in any brain region or spinal cord. Hsp27 decreased in the cerebellum, brainstem and spinal cord. Protein-bound SH base, non-protein SH base and total glutathione decreased in every brain region. CK activity decreased dose-dependently at 200 ppm or over, and the ratio of CK activity to CK-B concentration tended to decrease in all regions. The decrease in γ-enolase in the cerebrum suggests the involvement of biochemical changes in neurons with decrease in the wet weight of the cerebrum. Glutathione depletion and changes in proteins containing SH base as a critical site might be the underlying neurotoxic mechanism of 1-Bromopropane. The biochemical changes in the cerebrum indicate that long-term exposure to 1-Bromopropane has effects on the CNS.

  • Exposure to 1-Bromopropane Causes Ovarian Dysfunction in Rats
    Toxicological sciences : an official journal of the Society of Toxicology, 2003
    Co-Authors: Tetsuya Yamada, Gaku Ichihara, Hailan Wang, Michihiro Kamijima, Kei-ichiro Maeda, Hiroko Tsukamura, Tamie Nakajima, Yasuhiro Takeuchi
    Abstract:

    Although 1-Bromopropane has been used in chemical and electronic industries as an alternative to ozone layer-depleting solvents, its toxicity on female reproductive organs has not been fully elucidated. The aim of this experiment was to determine the effect of 1-Bromopropane on female reproductive function in rats. Forty female Wistar rats were divided into four equal groups. Each group was exposed daily to 0, 200, 400, or 800 ppm of 1-Bromopropane for eight h a day. After exposure for 7 weeks, all rats in the 800-ppm group became seriously ill and were sacrificed during the 8th week. The other dose groups were exposed for 12 weeks. In the 800-ppm group, but not in the other two exposed groups, body weight was significantly less than the control at each time point from 2 to 7 weeks after the beginning of exposure. Tests of vaginal smears showed a significant increase in the number of irregular estrous cycles with extended diestrus in the 400- and 800-ppm groups. Histopathological examination of the ovary showed a significant dose-dependent reduction of the number of normal antral follicles and a decrease in the number of normal growing follicles in the 400-ppm group. No significant change was found in plasma concentrations of LH or FSH in any group when compared with the control. Our results indicate that 1-Bromopropane can induce a dose-dependent ovarian dysfunction in nonpregnant female rats associated with disruption in follicular growth process.

Sahoko Ichihara - One of the best experts on this subject based on the ideXlab platform.

  • Role of cytochrome P450s in the male reproductive toxicity of 1-Bromopropane.
    Toxicology research, 2016
    Co-Authors: Cai Zong, C. Edwin Garner, Chinyen Huang, Xiao Zhang, Jie Chang, Masashi Kato, Toshihiro Sakurai, Sahoko Ichihara, Gaku Ichihara
    Abstract:

    1-Bromopropane (1BP) is widely used as an alternative to ozone-depleting solvents. The present study investigated the role of P450s in 1BP-induced male reproductive toxicity. Mice co-treated with 1-aminobenzotriazole (ABT), a non-selective P450 inhibitor, were exposed to 1BP at 0, 50, 250, or 1200 ppm, while saline-treated control mice were exposed to 1BP at 0, 50, or 250 ppm, for 4 weeks. In the saline-treated mice, exposure to 1BP at 250 ppm decreased the sperm count and sperm motility. Histopathological examination showed that exposure to 1BP at 50 and 250 ppm increased the number of elongated spermatids retained at the basal region of stage IX, X and XI seminiferous tubules, while exposure to 1BP at 250 ppm increased the number of periodic acid-Schiff (PAS)-positive round structures in stage IX, X, and XI seminiferous tubules. Co-treatment with ABT prevented the above changes induced by exposure to 1BP at 50 or 250 ppm. However, ABT-treated mice exposed to 1BP in the 1200 ppm group showed decreases in the weights of reproductive organs, epididymal sperm count and motility, increases in epididymal sperm with abnormal heads, retained spermatids and PAS-positive round structures in stages IX–XI, depletion of spermatogenic cells in part of the seminiferous tubules, and a small number of round spermatids in stage VII seminiferous tubules. The results at 50 and 250 ppm of 1-BP exposure indicate that P450s play important roles in 1BP-induced testicular toxicity. The control of P450 activity reduced 1BP-induced male reproductive toxicities including spermiation failure, reduction of epididymal sperm count and motility, and formation of PAS-positive round structures at postspermiation stages.

  • Hippocampal phosphoproteomics of F344 rats exposed to 1-Bromopropane.
    Toxicology and applied pharmacology, 2014
    Co-Authors: Zhenlie Huang, Lingyi Zhang, Jie Chang, Sahoko Ichihara, Shinji Oikawa, Hanlin Huang, Gaku Ichihara
    Abstract:

    1-Bromopropane (1-BP) is neurotoxic in both experimental animals and human. To identify phosphorylated modification on the unrecognized post-translational modifications of proteins and investigate their role in 1-BP-induced neurotoxicity, changes in hippocampal phosphoprotein expression levels were analyzed quantitatively in male F344 rats exposed to 1-BP inhalation at 0, 400, or 1000 ppm for 8 h/day for 1 or 4 weeks. Hippocampal protein extracts were analyzed qualitatively and quantitatively by Pro-Q Diamond gel staining and SYPRO Ruby staining coupled with two-dimensional difference in gel electrophoresis (2D-DIGE), respectively, as well as by matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) to identify phosphoproteins. Changes in selected proteins were further confirmed by Manganese II (Mn2 +)-Phos-tag SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Bax and cytochrome c protein levels were determined by western blotting. Pro-Q Diamond gel staining combined with 2D-DIGE identified 26 phosphoprotein spots (p < 0.05), and MALDI-TOF/MS identified 18 up-regulated proteins and 8 down-regulated proteins. These proteins are involved in the biological process of response to stimuli, metabolic processes, and apoptosis signaling. Changes in the expression of phosphorylated 14-3-3 θ were further confirmed by Mn2 +-Phos-tag SDS-PAGE. Western blotting showed overexpression of Bax protein in the mitochondria with down-regulation in the cytoplasm, whereas cytochrome c expression was high in the cytoplasm but low in the mitochondria after 1-BP exposure. Our results suggest that the pathogenesis of 1-BP-induced hippocampal damage involves inhibition of antiapoptosis process. Phosphoproteins identified in this study can potentially serve as biomarkers for 1-BP-induced neurotoxicity.

  • Effects of sub-acute and sub-chronic inhalation of 1-Bromopropane on neurogenesis in adult rats.
    Toxicology, 2012
    Co-Authors: Lingyi Zhang, Sahoko Ichihara, Taku Nagai, Kiyofumi Yamada, Daisuke Ibi, Kaviarasan Subramanian, Zhenlie Huang, Sahabudeen Sheik Mohideen, Hisao Naito, Gaku Ichihara
    Abstract:

    a b s t r a c t Purpose: 1-Bromopropane (1-BP) intoxication is associated with depression and cognitive and memory deficits. The present study tested the hypothesis that 1-BP suppresses neurogenesis in the dentate gyrus, which is involved in higher cerebral function, in adult rats.

  • Neurotoxicity of 1-Bromopropane: Evidence from animal experiments and human studies
    Journal of Advanced Research, 2012
    Co-Authors: Gaku Ichihara, Xuncheng Ding, Junzoh Kitoh, Sahoko Ichihara, Yasuhiro Takeuchi
    Abstract:

    Abstract 1-Bromopropane was introduced as an alternative to ozone layer-depleting solvents such as chlorofluorocarbons and 1,1,1-trichloroethane. However, a dozen human cases have been reported with symptoms and signs of toxicity to 1-Bromopropane including numbness, diminished vibration sense in the lower extremities as well as ataxic gait. An epidemiological study also demonstrated dose-dependent prolongation of distal latency and decrease in vibration sense in the lower extremities. The initial animal experiments helped to identify and analyze the initial human case of 1-Bromopropane toxicity. However, animal data that can explain the central nervous system disorders in humans are limited. Nonetheless, animal data should be carefully interpreted especially in a high-order function of the central nervous system or neurological signs such as ataxia that is influenced by fundamental anatomical/physiological differences between humans and animals. Enzymatic activity in the liver may explain partly the difference in the susceptibility between humans and animals, but further studies are needed to clarify the biological factors that can explain the difference and commonality among the species.

  • Proteomic analysis of hippocampal proteins of F344 rats exposed to 1-Bromopropane.
    Toxicology and applied pharmacology, 2011
    Co-Authors: Zhenlie Huang, Lingyi Zhang, Jie Chang, Sahoko Ichihara, Kaviarasan Subramanian, Sahabudeen Sheik Mohideen, Shinji Oikawa, Masahide Takahashi, Yun Wang, Gaku Ichihara
    Abstract:

    1-Bromopropane (1-BP) is a compound used as an alternative to ozone-depleting solvents and is neurotoxic both in experimental animals and human. However, the molecular mechanisms of the neurotoxic effects of 1-BP are not well known. To identify the molecular mechanisms of 1-BP-induced neurotoxicity, we analyzed quantitatively changes in protein expression in the hippocampus of rats exposed to 1-BP. Male F344 rats were exposed to 1-BP at 0, 400, or 1000 ppm for 8h/day for 1 or 4 weeks by inhalation. Two-dimensional difference in gel electrophoresis (2D-DIGE) combined with matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) were conducted to detect and identify protein modification. Changes in selected proteins were further confirmed by western blot. 2D-DIGE identified 26 proteins with consistently altered model (increase or decrease after both 1- and 4-week 1-BP exposures) and significant changes in their levels (p

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