Selenium (Se) is an indispensable trace mineral that was associated with liver injuries in animal models. Hydrogen sulfide (H2S) is involved in many liver diseases, and autophagy can maintain liver homeostasis with a stress stimulation. However, little is known about the correlation between H2S and autophagy in the liver injury chicken models induced by Se deficiency. In this study, we aimed to investigate the correlation between H2S and autophagy in the liver injury chicken models. We randomly divided 120 1-day-old chickens into two equal groups. The control group was fed with complete food with a Se content of 0.15 mg/kg, and the Se-deficiency group (lab group) was fed with a Se-deficient diet with a Se content of 0.033 mg/kg. When the time comes to 15, 25, and 35 days, the chickens were sacrificed (20 each). The liver tissues were gathered and examined for pathological observations, the mRNA and protein levels of H2S synthases (CSE, CBS, and 3-MST) and the mRNA and protein levels of autophagy-related genes. The results showed that the expression of CSE, CBS, and 3-MST and H2S production were higher in the lab group than in the control group. Swellings, fractures, and vacuolizations were visible in the mitochondria cristae in the livers of the lab group and autophagosomes were found as well. In addition, the expression of autophagy-related genes (ATG5, LC3-I, LC3-II, Beclin1, and Dynein) was higher in the lab group than in the control group (p < 0.05) while TOR decreased significantly in the lab group (p < 0.05). The results showed that H2S and autophagy were involved in the liver injury chicken models, and H2S was correlated with autophagy.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price includes VAT (USA)
Tax calculation will be finalised during checkout.
Ulrich S, Lutz S, Savaskan NE (2004) The neurobiology of selenium: lessons from transgenic mice. J Nutr 134(4):707–710
McCann JC, Ames BN (2011) Adaptive dysfunction of selenoproteins from the perspective of the triage theory: why modest selenium deficiency may increase risk of diseases of aging. FASEB J 25(6):1793–1814
Hoffmann PR, Claude JLS, Hoffmann FW, Chang PS, Oana B, Qingping H, Tam EK, Berry MJ (2007) A role for dietary selenium and selenoproteins in allergic airway inflammation. J Immunol 179(5):3258–3267
Guo M, Lv T, Liu F, Yan H, Wei T, Cai H, Tian W, Zhang N, Wang Z, Xie G (2013) Dietary selenium influences calcium release and activation of MLCK in uterine smooth muscle of rats. Biol Trace Elem Res 154(1):127–133
Moustafa ME, Carlson BA, Anver MR, Gerd B, Nianxin Z, Ward JM, Perella CM, Hoffmann VJ, Keith R, Combs GF (2013) Selenium and selenoprotein deficiencies induce widespread pyogranuloma formation in mice, while high levels of dietary selenium decrease liver tumor size driven by TGFα. Plos One 8(2):e57389
González-Pérez JM, González-Reimers E, Delavega-Prieto MJ, Viña-Rodríguez J, Galindo-Martín L, Alvisa-Negrín J, Santolaria-Fernández F (2011) Relative and combined effects of ethanol and protein deficiency on bone manganese and copper. Biol Trace Elem Res 147(1–3):226–232
Osame S, Ohtani T, Ichijo S (1990) Studies on serum tocopherol and selenium levels and blood glutathione peroxidase activities in lambs with white muscle disease. Nippon Juigaku Zasshi Jpn J Vet Sci 52(4):705–710
Xing Y, Liu Z, Yang G, Gao D, Niu X (2015) MicroRNA expression profiles in rats with selenium deficiency and the possible role of the Wnt/β-catenin signaling pathway in cardiac dysfunction. Int J Mol Med 35(1):143–152
Li JL, Rui G, Shu L, Wang JT, Tang ZX, Xu SW (2010) Testicular toxicity induced by dietary cadmium in cocks and ameliorative effect by selenium. Biometals 23(4):695–705
Yao HD, Wu Q, Zhang ZW, Li S, Wang XL, Lei XG, Xu SW (2013) Selenoprotein W serves as an antioxidant in chicken myoblasts. Biochim Biophys Acta 1830(4):3112–3120. doi:10.1016/j.bbagen.2013.01.007
Burk RF, Hill KE, Motley AK (2003) Selenoprotein metabolism and function: evidence for more than one function for selenoprotein P. J Nutr 133(5 Suppl 1):1517S–1520S
Zhang ZW, Zhang JL, Zhang YH, Wang QH, Li S, Wang XL, Xu SW (2013) Effect of oxygen free radicals and nitric oxide on apoptosis of immune organ induced by selenium deficiency in chickens. Biol Met 26(2):355–365
Sumpter R, Levine B (2010) Autophagy and innate immunity: triggering, targeting and tuning. Semin Cell Dev Biol 21(21):699–711
Schneider PD, Gorschboth CM (1983) Limiting ischemic liver injury by interfering with lysosomal autophagy. J Surg Res 34(6):550–554
Kudchodkar SB, Levine B (2009) Viruses and autophagy. Rev Med Virol 19(6):359–378
Yan C, Ugir Hossain S, Yi Z, Xingcong R, Li Z, Huber-Keener KJ, Yuan-Wan S, Jason L, Shantu A, Sharma AK (2012) Rational incorporation of selenium into temozolomide elicits superior antitumor activity associated with both apoptotic and autophagic cell death. Plos One 7(4):40–41
Santosh K, Mehta SL, Li PA (2012) Glutamate induces mitochondrial dynamic imbalance and autophagy activation: preventive effects of selenium. Plos One 7(6):e39382
Rui W (2014) Gasotransmitters: growing pains and joys. Trends Biochem Sci 39(5):227–232
Olas B (2015) Hydrogen sulfide in signaling pathways. Clin Chim Acta 439C:212–218
Searcy DG, Lee SH (1998) Sulfur reduction by human erythrocytes. J Exp Zool 282(3):310–322
Lowicka E, Beltowski J (2007) Hydrogen sulfide (H2S)—the third gas of interest for pharmacologists. Pharmacol Rep 59(1):4–24
Zhao W, Zhang J, Lu Y, Wang R (2001) The vasorelaxant effect of H2S as a novel endogenous gaseous KATP channel opener. EMBO J 20(21):6008–6016
Yasuo N, Mamiko T, Jun-Ichiro O, Hideo K (2004) Hydrogen sulfide induces calcium waves in astrocytes. FASEB J 18(3):557–559
Li L, Bhatia M, Zhu YZ, Zhu YC, Ramnath RD, Wang ZJ, Anuar FB, Whiteman M, Salto-Tellez M, Moore PK (2005) Hydrogen sulfide is a novel mediator of lipopolysaccharide-induced inflammation in the mouse. FASEB J 19(9):1196–1198
Mani S, Cao W, Wu L, Wang R (2014) Hydrogen sulfide and the liver. Nitric Oxide Biol Chem 41(18):62–71
Cheng P, Wang F, Chen K, Shen M, Dai W, Xu L, Zhang Y, Wang C, Li J, Yang J (2014) Hydrogen sulfide ameliorates ischemia/reperfusion-induced hepatitis by inhibiting apoptosis and autophagy pathways. Mediat Inflamm 2014(2):142
Li L, Jiang HK, Li YP, Guo YP (2015) Hydrogen sulfide protects spinal cord and induces autophagy via miR-30c in a rat model of spinal cord ischemia-reperfusion injury. J Biomed Sci 22:50. doi:10.1186/s12929-015-0135-1
Liu C (2015) The role of nitric oxide and autophagy in liver injuries induced by selenium deficiency in chickens. RSC Adv 5(62):50549–50556
Ji-He LI, Tong DX, Xin-Bing XU, Han BQ, Wang XC (2011) Changes and significance of myocardial H2S/CSE system in endotoxemic rats. J Harbin Med Univ
Jr BR, Bus JS, Popp JA, Boreiko CJ, Andjelkovich DA (2008) A critical review of the literature on hydrogen sulfide toxicity. Crit Rev Toxicol 13(1):25–97
Reiffenstein RJ, And WCH, Roth SH (1992) Toxicology of hydrogen sulfide. Annu Rev Pharmacol Toxicol 32(32):109–134
Yoshinori M, Norihiro S, Yuki O, Hideo K (2013) Hydrogen sulfide is produced by cystathionine γ-lyase at the steady-state low intracellular Ca2+ concentrations. Biochem Biophys Res Commun 431(2):131–135
Abe K, Kimura H (1996) The possible role of hydrogen sulfide as an endogenous neuromodulator. J Neurosci 16(3):1066–1071
Yoshinori M, Norihiro S, Yuka K, Noriyuki N, Masahiro Y, Hideo K (2011) Hydrogen sulfide protects the retina from light-induced degeneration by the modulation of Ca2+ influx. J Biol Chem 286(45):39379–39386
Huang CW, Moore PK (2015) H2S synthesizing enzymes: biochemistry and molecular aspects. Handb Exp Pharmacol 230:3–25
Doeller JE, Isbell TS, Benavides G, Koenitzer J, Patel H, Patel RP, Jr LJ, Darley-Usmar VM, Kraus DW (2005) Polarographic measurement of hydrogen sulfide production and consumption by mammalian tissues. Anal Biochem 341(1):40–51
Chen Y, Mo HZ, Zheng MY, Xian M, Qi ZQ, Li YQ, Hu LB, Chen J, Yang LF (2014) Selenium inhibits root elongation by repressing the generation of endogenous hydrogen sulfide in Brassica rapa. Plos One 9(10):e110904
Zhou X, An G, Chen J (2014) Hydrogen sulfide improves left ventricular function in smoking rats via regulation of apoptosis and autophagy. Apoptosis Int J Prog Cell Death 19(6):998–1005
Bekpinar S, Unlucerci Y, Uysal M, Gurdol F (2014) Propargylglycine aggravates liver damage in LPS-treated rats: possible relation of nitrosative stress with the inhibition of H2S formation. Pharmacol Rep 66(5):897–901
Yao H, Liu W, Zhao W, Fan R, Zhao X, Khoso PA, Zhang Z, Xu S (2014) Different responses of selenoproteins to the altered expression of selenoprotein W in chicken myoblasts. RSC Adv 4(109):64032–64042
Jiang ZH (2015) SelW regulates inflammation-related cytokines in response to H2O2 in Se-deficient chicken liver. RSC Adv 5(47):37896–37905
Zhang Z, Wang J, Li J, Xu S (2011) Telomerase-mediated apoptosis of chicken lymphoblastoid tumor cell line by lanthanum chloride. Biol Trace Elem Res 144(1–3):657–667
Matsumoto K, Ui I, Satoh K, Tobe T, Ushio F, Endo K (2002) Evaluation of oxidative damage in the liver of selenium-deficient rats. Redox Rep 7(5):351–354
Burk RF, Hill KE, Nakayama A, Mostert V, Levander XA, Motley AK, Johnson DA, Johnson JA, Freeman ML, Austin LM (2008) Selenium deficiency activates mouse liver Nrf2-ARE but vitamin E deficiency does not. Free Radic Biol Med 44(8):1617–1623
Cheng WH, Quimby FW, Lei XG (2003) Impacts of glutathione peroxidase-1 knockout on the protection by injected selenium against the pro-oxidant-induced liver aponecrosis and signaling in selenium-deficient mice. Free Radic Biol Med 34(34):918–927
Codogno P, Meijer AJ (2013) Autophagy in the liver. J Hepatol 59(2):389–391
Czaja MJ, Wen-Xing D, Donohue TM, Friedman SL, Jae-Sung K, Masaaki K, Lemasters JJ, Antoinette L, Lin JD, Jing-Hsiung James O (2013) Functions of autophagy in normal and diseased liver. Autophagy 9(8):1131–1158
Wu JC, Wang FZ, Tsai ML, Lo CY, Badmaev V, Ho CT, Wang YJ, Pan MH (2015) Se-allylselenocysteine induces autophagy by modulating the AMPK/mTOR signaling pathway and epigenetic regulation of PCDH17 in human colorectal adenocarcinoma cells. Mol Nutr Food Res 59(12):2511–2522. doi:10.1002/mnfr.201500373
Shibutani ST, Saitoh T, Nowag H, Münz C, Yoshimori T (2015) Autophagy and autophagy-related proteins in the immune system. Nat Immunol 16(10):1014–1024
Mizushima N, Sugita H, Yoshimori T, Ohsumi Y (1998) A new protein conjugation system in human. The counterpart of the yeast Apg12p conjugation system essential for autophagy. J Biol Chem 273(51):33889–33892
Mcleland CB, Rodriguez J, Stern ST (2011) Autophagy monitoring assay: qualitative analysis of MAP LC3-I to II conversion by immunoblot. Methods Mol Biol 697:199–206
Hwa JC, Seung-Hyun R, Jing C, Neil Michael O, Do-Hyung K (2010) mTOR regulation of autophagy. FEBS Lett 584(7):1287–1295
Brinda R, Abraham AA, Sara I, Zdenek B, Coralie V, O’Kane CJ, Brown SDM, Rubinsztein DC (2005) Dynein mutations impair autophagic clearance of aggregate-prone proteins. Nat Genet 37(7):771–776
Jiang H, Jian X, Bo K, Zhu X, Ni X, Wang Z (2015) PI3K/SGK1/GSK3β signaling pathway is involved in inhibition of autophagy in neonatal rat cardiomyocytes exposed to hypoxia/reoxygenation by hydrogen sulfide. Exp Cell Res. doi:10.1016/j.yexcr.2015.07.005
Kundu S, Pushpakumar S, Khundmiri SJ, Sen U (2014) Hydrogen sulfide mitigates hyperglycemic remodeling via liver kinase B1-adenosine monophosphate-activated protein kinase signaling. Biochim Biophys Acta 1843(12):2816–2826
Dawei W, Yong M, Zhengtian L, Kai K, Xueying S, Shangha P, Jizhou W, Huayang P, Lianxin L, Desen L (2012) The role of AKT1 and autophagy in the protective effect of hydrogen sulphide against hepatic ischemia/reperfusion injury in mice. Autophagy 8(6):954–962
All other authors have read the manuscript and have agreed to submit it in its current form for consideration for publication in the journal. No papers will be processed without this requisite.
All procedures used in the present study were approved by the Institutional Animal Care and Use Committee of Northeast Agricultural University.
Conflict of Interest
The authors declare that they have no conflict of interest.
Informed consent was obtained from all individual participants included in this study.
Wang Wenzhong and Zhang Tong contributed equally to this work.
About this article
Cite this article
Wenzhong, W., Tong, Z., Hongjin, L. et al. Role of Hydrogen Sulfide on Autophagy in Liver Injuries Induced by Selenium Deficiency in Chickens. Biol Trace Elem Res 175, 194–203 (2017). https://doi.org/10.1007/s12011-016-0752-x
- Selenium deficiency
- Hydrogen sulfide