Skip to main content
Log in

Alleviation Mechanisms of Selenium on Cadmium-Spiked in Chicken Ovarian Tissue: Perspectives from Autophagy and Energy Metabolism

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Cadmium (Cd) is a kind of toxic heavy metal and it can cause damage to organs and tissues. Selenium (Se) can antagonize some metal element toxicity including Cd. The present study was designed to investigate Cd-induced damage to chicken ovary by autophagy and the protective mechanism of Se on Cd-induced damage. Administration of Cd for 12 weeks led to energy metabolism disorder of the chicken ovarian tissues, which resulted in autophagy. In addition, the mRNA expression of glucose-related genes including hexokinase II (HK2), pyruvate kinase (PK), pyruvate dehydrogenase complex (PDHX), and succinate dehydrogenase (SDH) and the activities of ATPase, including Na+-K+-ATPase, Ca2+-ATPase, Mg2+-ATPase, were all downregulated remarkably compared with the control. However, combined with oral administration of Se at 2 mg/kg, the mRNA expression of glucose-related genes and the activities of ATPase increased. The mRNA expression of the autophagy-related genes by Cd treatment, including microtubule-associated protein light chain 3 (LC3), dynein, autophagy-related gene 5 (Atg5), and Beclin 1, was remarkably enhanced, whereas mammalian target of rapamycin (mTOR) was downregulated. However, besides mTOR, their levels displayed a downregulated trend beyond simultaneous Se treatment. The protein expression of autophagy genes was similar to those of mRNA. In conclusion, Cd toxicity affect energy metabolism and induce autophagy, which causes damage to chicken ovary, whereas Se could protect effectively this injury induced by Cd.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

Cd:

Cadmium

Se:

Selenium

HK2:

Hexokinase II

PK:

Pyruvate kinase

PDHX:

Pyruvate dehydrogenase complex

SDH:

Succinate dehydrogenase

LC3:

Microtubule-associated protein light chain 3

mTOR:

Mammalian target of rapamycin

Atg5:

Autophagy-related gene 5

q-PCR:

Quantitative real-time polymerase chain reaction

References

  1. Koyu A, Gokcimen A, Ozguner F, Bayram DS, Kocak A (2006) Evaluation of the effects of cadmium on rat liver. Mol Cell Biochem 284(1):81–85

    Article  CAS  Google Scholar 

  2. Thijssen S, Maringwa J, Faes C, Lambrichts I, Van KE (2007) Chronic exposure of mice to environmentally relevant, low doses of cadmium leads to early renal damage, not predicted by blood or urine cadmium levels. Toxicology 229(1–2):145–156

    Article  CAS  Google Scholar 

  3. Saksena SK, Dahlgren L, Lau IF, Chang MC (1977) Reproductive and endocrinological features of male rats after treatment with cadmium chloride. Biol Reprod 16(5):609–613

    Article  CAS  Google Scholar 

  4. Haouem S, Hmad N, Najjar MF, El HA, Sakly R (2007) Accumulation of cadmium and its effects on liver and kidney functions in rats given diet containing cadmium-polluted radish bulb. Exp Toxicol Pathol Off J Gesellschaft Für Toxikologische Pathologie 59(1):77–80

    Article  CAS  Google Scholar 

  5. Kluxen FM, Höfer N, Kretzschmar G, Degen GH, Diel P (2012) Cadmium modulates expression of aryl hydrocarbon receptor-associated genes in rat uterus by interaction with the estrogen receptor. Arch Toxicol 86(4):591–601

    Article  CAS  Google Scholar 

  6. Zhang W, Pang F, Huang Y, Yan P, Lin W (2008) Cadmium exerts toxic effects on ovarian steroid hormone release in rats. Toxicol Lett 182(1–3):18–23

    Article  CAS  Google Scholar 

  7. Höfer N, Diel P, Wittsiepe J, Wilhelm M, Degen GH (2009) Dose- and route-dependent hormonal activity of the metalloestrogen cadmium in the rat uterus. Toxicol Lett 191(2–3):123–131

    Article  Google Scholar 

  8. Sheng Y, Sun B, Guo WT, Zhang YH, Liu X, Xing Y, Dong DL (2013) 3-Methyladenine induces cell death and its interaction with chemotherapeutic drugs is independent of autophagy. Biochem Biophys Res Commun 432(1):5–9

    Article  CAS  Google Scholar 

  9. Xue L, Fletcher GC, Tolkovsky AM (1999) Autophagy is activated by apoptotic signalling in sympathetic neurons: an alternative mechanism of death execution. Mol Cellu Neurosci 14(3):180–198

    Article  CAS  Google Scholar 

  10. Lim SC, Hahm KS, Lee SH, Oh SH (2010) Autophagy involvement in cadmium resistance through induction of multidrug resistance-associated protein and counterbalance of endoplasmic reticulum stress WI38 lung epithelial fibroblast cells. Toxicology 276(1):18–26

    Article  CAS  Google Scholar 

  11. Chen M, Li X, Fan R, Yang J, Jin X, Hamid S, Xu S (2017) Cadmium induces BNIP3-dependent autophagy in chicken spleen by modulating miR-33-AMPK axis. Chemosphere 194:396–402

    Article  Google Scholar 

  12. Eisenberglerner A, Kimchi A (2009) The paradox of autophagy and its implication in cancer etiology and therapy. Apoptosis 14(4):376–391

    Article  Google Scholar 

  13. Woods A, Heath R, Dickerson K, Hong SP, Momcilovic M, Johnstone SR, Carlson M, Carling D (2005) Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells. Cell Metab 2(1):21–33

    Article  CAS  Google Scholar 

  14. Mizushima N (2004) Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes. Nat Cell Biol 6(6):1221–1228

    PubMed  Google Scholar 

  15. Wang SH, Shih YL, Kuo TC, Ko WC, Shih CM (2009) Cadmium toxicity toward autophagy through ROS-activated GSK-3β in mesangial cells. Toxicol Sci 108(1):124–131

    Article  CAS  Google Scholar 

  16. Dong Z, Wang L, Xu J, Li Y, Zhang Y, Zhang S, Miao J (2009) Promotion of autophagy and inhibition of apoptosis by low concentrations of cadmium in vascular endothelial cells. Toxicol in Vitro 23(1):105–110

    Article  CAS  Google Scholar 

  17. Ramírez-Peinado S, León-Annicchiarico C, Iurlaro R, Muñoz-Pinedo C (2012) Cell death induced by inhibition of glucose metabolism: role of Bcl-2 proteins and autophagy. Exp Clin Endocrinol Diabetes 120(10):567–638

    Article  Google Scholar 

  18. Moruno-Manchón JF, Pérez-Jiménez E, Knecht E (2013) Glucose induces autophagy under starvation conditions by a p38 MAPK-dependent pathway. Biochem J 449(2):497–506

    Article  Google Scholar 

  19. Lock R, Roy S, Kenific CM, Su JS, Salas E, Ronen SM, Debnath J (2011) Autophagy facilitates glycolysis during Ras-mediated oncogenic transformation. Mol Biol Cell 22(2):165–178

    Article  CAS  Google Scholar 

  20. Yao HD, Wu Q, Zhang ZW, Zhang JL, Li S, Huang JQ, Ren FZ, Xu SW, Wang XL, Lei XG (2013) Gene expression of endoplasmic reticulum resident selenoproteins correlates with apoptosis in various muscles of se-deficient chicks. J Nutr 143(5):613–619

    Article  CAS  Google Scholar 

  21. El-Sharaky AS, Newairy AA, Badreldeen MM, Eweda SM, Sheweita SA (2007) Protective role of selenium against renal toxicity induced by cadmium in rats. Toxicology 235(3):185–193

    Article  CAS  Google Scholar 

  22. 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

    Article  CAS  Google Scholar 

  23. Li X, Xing M, Chen M, Zhao J, Fan R, Xia Z, Cao C, Jie Y, Zhang Z, Xu S (2017) Effects of selenium-lead interaction on the gene expression of inflammatory factors and selenoproteins in chicken neutrophils. Ecotoxicol Environ Safety 139:447–453

    Article  CAS  Google Scholar 

  24. Jin X, Xu Z, Zhao X, Chen M, Xu S (2017) The antagonistic effect of selenium on lead-induced apoptosis via mitochondrial dynamics pathway in the chicken kidney. Chemosphere 180:259–266

    Article  CAS  Google Scholar 

  25. Yao HD, Wu Q, Zhang ZW, Shu L, Wang XL, Lei XG, Xu SW (2013) Selenoprotein W serves as an antioxidant in chicken myoblasts. Biochim Biophys Acta 1830(4):3112–3120

    Article  CAS  Google Scholar 

  26. Messaoudi I, El HJ, Hammouda F, Saïd K, Kerkeni A (2009) Protective effects of selenium, zinc, or their combination on cadmium-induced oxidative stress in rat kidney. Biol Trace Elem Res 130(2):152–161

    Article  CAS  Google Scholar 

  27. Ognjanovic B, Markovic S, Pavlovic S, Zikic R, As SZ (2008) Effect of chronic cadmium exposure on antioxidant defense system in some tissues of rats: protective effect of selenium. Physiol Res 57(3):403–411

    CAS  PubMed  Google Scholar 

  28. Lazarus M, Orct T, Jurasoviæ J, Blanuša M (2009) The effect of dietary selenium supplementation on cadmium absorption and retention in suckling rats. Biometals 22(6):973–983

    Article  CAS  Google Scholar 

  29. Pappas AC, Zoidis E, Georgiou CA, Demiris N, Surai PF, Fegeros K (2011) Influence of organic selenium supplementation on the accumulation of toxic and essential trace elements involved in the antioxidant system of chicken. Food Addit Contam Part A Chem Anal Control Exposure Risk Assess 28(4):446–454

    Article  CAS  Google Scholar 

  30. Alwaeli A, Zoidis E, Pappas AC, Demiris N, Zervas G, Fegeros K (2013) The role of organic selenium in cadmium toxicity: effects on broiler performance and health status. Animal 7(3):386–393

    Article  CAS  Google Scholar 

  31. Pinto A, Juniper DT, Sanil M, Morgan L, Clark L, Sies H, Rayman MP, Steinbrenner H (2012) Supranutritional selenium induces alterations in molecular targets related to energy metabolism in skeletal muscle and visceral adipose tissue of pigs. J Inorg Biochem 114(9):47–54

    Article  CAS  Google Scholar 

  32. Liu C, Fu J, Liu C, Li S (2015) The role of nitric oxide and autophagy in liver injuries induced by selenium deficiency in chickens. RSC Adv 5(62):50549–50556

    Article  CAS  Google Scholar 

  33. Frustaci A, Sabbioni E, Fortaner S, Farina M, Torchio RD, Tafani M, Morgante E, Ciriolo MR, Russo MA, Chimenti C (2012) Selenium- and zinc-deficient cardiomyopathy in human intestinal malabsorption: preliminary results of selenium/zinc infusion. Eur J Heart Fail 14(2):202–210

    Article  CAS  Google Scholar 

  34. Tan S, Chi Q, Liu T, Sun Z, Min Y, Zhang Z, Shu L (2017) Alleviation mechanisms of selenium on cadmium-spiked neutrophil injury to chicken. Biol Trace Elem Res 178:301–309

    Article  CAS  Google Scholar 

  35. Wang L, Li J, Li J, Liu Z (2010) Effects of lead and/or cadmium on the oxidative damage of rat kidney cortex mitochondria. Biol Trace Elem Res 137(1):69–78

    Article  CAS  Google Scholar 

  36. Krstić D, Krinulović K, Vasić V (2005) Inhibition of Na+-K+-ATPase and Mg2+-ATPase by metal ions and prevention and recovery of inhibited activities by chelators. J Enzyme Inhib Med Chem 20(5):469–476

    Article  Google Scholar 

  37. Kim H, Lim B, Kim BD, Lee YM (2016) Effects of heavy metals on transcription and enzyme activity of Na+-K+-ATPase in the monogonont rotifer, Brachionus koreanus. Toxicol Environ Heal Sci 8(2):128–134

    Article  Google Scholar 

  38. Canesi L, Ciacci C, Piccoli G, Stocchi V, Viarengo A, Gallo G (1998) In vitro and in vivo effects of heavy metals on mussel digestive gland hexokinase activity: the role of glutathione. Comp Biochem Physiol C: Pharmacol Toxicol Endocrinol 120(2):261–268

    CAS  Google Scholar 

  39. Pysher MD, Sollome JJ, Regan S, Cardinal TR, Hoying JB, Brooks HL, Vaillancourt RR (2007) Increased hexokinase II expression in the renal glomerulus of mice in response to arsenic. Toxicol Appl Pharmacol 224(1):39–48

    Article  CAS  Google Scholar 

  40. Lin G, Andrejeva G, Ac WTF, Hill DK, Orton MR, Parkes HG, Koh DM, Robinson SP, Leach MO, Eykyn TR (2014) Reduced Warburg effect in cancer cells undergoing autophagy: steady-state 1H-MRS and real-time hyperpolarized 13C-MRS studies. PLoS One 9(3):e92645

    Article  Google Scholar 

  41. Liu Y, Shoji-Kawata S, Jr SR, Wei Y, Ginet V, Zhang L, Posner B, Tran KA, Green DR, Xavier RJ (2013) Autosis is a Na+-K+-ATPase-regulated form of cell death triggered by autophagy-inducing peptides, starvation, and hypoxia-ischemia. Proc Natl Acad Sci U S A 110(51):20364–20371

    Article  CAS  Google Scholar 

  42. Z Y SJ, C Y LAJ, Heintz N (2003) Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc Natl Acad Sci U S A 100(25):15077–15082

    Article  Google Scholar 

  43. Cui J, Gong Z, Shen HM (2013) The role of autophagy in liver cancer: molecular mechanisms and potential therapeutic targets. Biochim Biophys Acta 1836(1):15–26

    CAS  PubMed  Google Scholar 

  44. Chargui A, Zekri S, Jacquillet G, Rubera I, Ilie M, Belaid A, Duranton C, Tauc M, Hofman P, Poujeol P (2011) Cadmium-induced autophagy in rat kidney: an early biomarker of subtoxic exposure. Toxicol Sci 121(1):31–42

    Article  CAS  Google Scholar 

  45. Zou H, Zhuo L, Han T, Hu D, Yang X, Wang Y, Yuan Y, Gu J, Bian J, Liu X (2015) Autophagy and gap junctional intercellular communication inhibition are involved in cadmium-induced apoptosis in rat liver cells. Biochem Biophys Rese Commun 459(4):713–719

    Article  CAS  Google Scholar 

  46. Banni M, Messaoudi I, Said L, Heni JE, Kerkeni A, Said K (2010) Metallothionein gene expression in liver of rats exposed to cadmium and supplemented with zinc and selenium. Arch Environ Contam Toxicol 59(3):513–519

    Article  CAS  Google Scholar 

  47. Taskin E, Dursun N (2015) Recovery of adriamycin induced mitochondrial dysfunction in liver by selenium. Cytotechnology 67(6):977–986

    Article  CAS  Google Scholar 

  48. Becker DJ, Reul B, Ozcelikay AT, Buchet JP, Henquin JC, Brichard SM (1996) Oral selenate improves glucose homeostasis and partly reverses abnormal expression of liver glycolytic and gluconeogenic enzymes in diabetic rats. Diabetologia 39(1):3–11

    Article  CAS  Google Scholar 

  49. Wang W, Zhang T, Lin H, Chang Y, Xing J (2016) Role of hydrogen sulfide on autophagy in liver injuries induced by selenium deficiency in chickens. Biol Trace Elem Res 175(1):194–203

    Google Scholar 

  50. Kumari S, Mehta SL, Li PA (2012) Glutamate induces mitochondrial dynamic imbalance and autophagy activation: preventive effects of selenium. PLoS One 7(6):e39382

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank the members of the Veterinary Internal Medicine Laboratory, College of Veterinary Medicine, Northeast Agriculture University, for their help with sample collection.

Funding

This study was supported by the National Natural Science Foundation of China (Grant No.31472161) and Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shu Li.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

All of the authors have read the manuscript and agreed to submit it in its current form for consideration for publication in the Biological Trace Element Research.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, S., Xu, Z., Yin, H. et al. Alleviation Mechanisms of Selenium on Cadmium-Spiked in Chicken Ovarian Tissue: Perspectives from Autophagy and Energy Metabolism. Biol Trace Elem Res 186, 521–528 (2018). https://doi.org/10.1007/s12011-018-1341-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-018-1341-y

Keywords

Navigation