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Effects of exogenous hydrogen sulfide on apoptosis proteins and oxidative stress in the hippocampus of rats undergoing heroin withdrawal

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Abstract

In this study, the mechanism of H2S protection in the hippocampus of heroin-treated rats was investigated. Male Sprague-Dawley rats were randomly divided into three groups: a saline group, a heroin and saline group, and a heroin and sodium hydrosulfide group. According to the principle of increasing heroin dosage daily, heroin withdrawal was precipitated on day 9 with an injection of naloxone (5 mg/kg, i.p.), and withdrawal symptoms were scored. The levels of cystathionine-β-synthase, H2S, reduced glutathione and malondialdehyde, as well as the levels of cleaved caspase-3, Bax, and Bcl-2 proteins and the activities of superoxide dismutase, catalase, and glutathione peroxidase were assayed in the hippocampus. The results showed that exogenous H2S alleviated heroin withdrawal symptoms. Moreover, exogenous H2S not only increased cellular H2S and the cystathionine-β-synthase protein level activity but also significantly improved heroin-induced oxidative stress. Protein expression of cleaved caspase-3 and Bax decreased, whereas Bcl-2 protein levels in hippocampus increased with exogenous H2S. Exogenous H2S alleviated heroin-induced rat hippocampal damage through antioxidant and antiapoptosis effects.

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References

  • Abe, K. and Kimura, H., The possible role of hydrogen sulfide as an endogenous neuromodulator. J. Neurosci., 16, 1066–1071 (1996).

    PubMed  CAS  Google Scholar 

  • Acehan, D., Jiang, X., Morgan, D. G., Heuser, J. E., Wang, X., and Akey, C. W., Three-dimensional structure of the apoptosome: implications for assembly, procaspase-9 binding, and activation. Mol. Cell, 9, 423–432 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Cunha-Oliveira, T., Rego, A. C., Garrido, J., Borges, F., Macedo, T., and Oliveira, C. R., Street heroin induces mitochondrial dysfunction and apoptosis in rat cortical neurons. J. Neurochem., 101, 543–554 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Ellman, G. and Lysko, H., A precise method for the determination of whole blood and plasma sulfhydryl groups. Anal. Biochem., 93, 98–102 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Fukamachi, Y., Karasaki, Y., Sugiura, T., Itoh, H., Abe, T., Yamamura, K., and Higashi, K., Zinc suppresses apoptosis of U937 cells induced by hydrogen peroxide through an increase of the Bcl-2/Bax ratio. Biochem. Biophys. Res. Commun., 246, 364–369 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Kobayashi, T., Ruan, S., Clodi, K., Kliche, K. O., Shiku, H., Andreeff, M., and Zhang, W., Overexpression of Bax gene sensitizes K562 erythroleukemia cells to apoptosis induced by selective chemotherapeutic agents. Oncogene, 16, 1587–1591 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Konstantinidou, A. E., Givalos, N., Gakiopoulou, H., Korkolopoulou, P., Kotsiakis, X., Boviatsis, E., Agrogiannis, G., Mahera, H., and Patsouris, E., Caspase-3 immunohistochemical expression is a marker of apoptosis, increased grade and early recurrence in intracranial meningiomas. Apoptosis, 12, 695–705 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J., Protein measurement with the Folin phenol reagent. J. Biol. Chem., 193, 265–275 (1951).

    PubMed  CAS  Google Scholar 

  • Luo, X. M., Pan, G. S., and Chen, Y. S., Effects of exogenous hydrogen sulfide on learning and memory of heroin-addictive rats. Acta Academiae Medicinae Zunyi, 32, 2108–2110 (2009).

    Google Scholar 

  • Moore, P. K., Bhatia, M., and Moochhala, S., Hydrogen sulfide: from the smell of the past to the mediator of the future? Trends Pharmacol. Sci., 24, 609–611 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Oltvai, Z. N., Milliman, C. L., and Korsmeyer, S. J., Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell, 74, 609–619 (1993).

    Article  PubMed  CAS  Google Scholar 

  • Oyanagui, Y., Reevaluation of assay methods and establishment of kit for superoxide dismutase activity. Anal. Biochem., 142, 290–296 (1984).

    Article  PubMed  CAS  Google Scholar 

  • Pan, J., Zhang, Q., Zhang, Y., Ouyang, Z., Zheng, Q., and Zheng, R., Oxidative stress in heroin administered mice and natural antioxidants protection. Life Sci., 77, 183–193 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Panchenko, L. F., Pirozhkov, S. V., and Nadezhdin, A. V., Lipid peroxidation, peroxyl radical-scavenging system of plasma and liver and heart pathology in adolescence heroin users. Vopr. Med. Khim., 45, 501–506 (1999).

    PubMed  CAS  Google Scholar 

  • Qu, K., Chen, C. P., Halliwell, B., Moore, P. K., and Wong, P. T., Hydrogen sulfide is a mediator of cerebral ischemic damage. Stroke, 37, 889–893 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Rasmussen, K., Kendriek, W. T., Kogan, J. H., and Aghajanian, G. K., A selective AMP antagonist, LY293558, suppresses morphine withdrawal induced activation of locus coeruleus neurons and behavioral signs of morphine withdrawal. Neuropsychopharmacology, 15, 497–505 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Ren, C., Du, A., Li, D., Sui, J., Mayhan, W. G., and Zhao, H., Dynamic change of hydrogen sulfide during global cerebral ischemia-reperfusion and its effect in rats. Brain Res., 1345, 197–205 (2010).

    Article  PubMed  CAS  Google Scholar 

  • Singhal, P. C., Pamarthi, M., Shah, R., Chandra, D., and Gibbons, N., Morphine stimulates superoxide formation by glomerular mesangial cells. Inflammation, 18, 293–299 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Tramullas, M., Martinez-Cue, C., and Hurle, M. A., Chronic administration of heroin to mice produces up-regulation of brain apoptosis-related proteins and impairs spatial learning and memory. Neuropharmacology, 54, 640–652 (2008).

    Article  PubMed  CAS  Google Scholar 

  • Wang, R., Two’s company, three’s a crowd: can H2S be the third endogenous gaseous transmitter? FASEB J., 16, 1792–1798 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Widlak, P. and Garrard, W. T., The apoptotic endonuclease DFF40/CAD is inhibited by RNA, heparin and other polyanions. Apoptosis, 11, 1331–1337 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Yu, P. Y., Ju. W. P., Li, Z. G., Wang, D. Z., Wang, Y. C., and Xie, A. M., Acupuncture inhibits oxidative stress and rotational behavior in 6-hydroxydopamine lesioned rat. Brain Res., 1336, 58–65 (2010).

    Article  PubMed  CAS  Google Scholar 

  • Zhou, J. F., Yan, X. F., Ruan, Z. R., Peng, F. Y., Cai, D., and Yuan, H., Heroin abuse and nitric oxide, oxidation, peroxidation, lipoperoxidation. Biomed. Environ. Sci., 13, 131–139 (2000).

    PubMed  CAS  Google Scholar 

  • Zhu, H. and Ho, I. K., NMDA-R1 antisense oligonucleotide attenuates withdrawal signs from morphine. Eur. J. Pharmacol., 352, 151–156 (1998).

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Li-he Jiang.

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Jiang, Lh., Luo, X., He, W.a. et al. Effects of exogenous hydrogen sulfide on apoptosis proteins and oxidative stress in the hippocampus of rats undergoing heroin withdrawal. Arch. Pharm. Res. 34, 2155–2162 (2011). https://doi.org/10.1007/s12272-011-1220-y

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  • DOI: https://doi.org/10.1007/s12272-011-1220-y

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