Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Capsaicin Ameliorates Cisplatin-Induced Renal Injury through Induction of Heme Oxygenase-1

  • Jung, Sung-Hyun (Center for Metabolic Function Regulation, Department of Microbiology, Wonkwang University School of Medicine) ;
  • Kim, Hyung-Jin (Center for Metabolic Function Regulation, Department of Microbiology, Wonkwang University School of Medicine) ;
  • Oh, Gi-Su (Center for Metabolic Function Regulation, Department of Microbiology, Wonkwang University School of Medicine) ;
  • Shen, AiHua (Center for Metabolic Function Regulation, Department of Microbiology, Wonkwang University School of Medicine) ;
  • Lee, Subin (Center for Metabolic Function Regulation, Department of Microbiology, Wonkwang University School of Medicine) ;
  • Choe, Seong-Kyu (Center for Metabolic Function Regulation, Department of Microbiology, Wonkwang University School of Medicine) ;
  • Park, Raekil (Center for Metabolic Function Regulation, Department of Microbiology, Wonkwang University School of Medicine) ;
  • So, Hong-Seob (Center for Metabolic Function Regulation, Department of Microbiology, Wonkwang University School of Medicine)
  • Received : 2013.11.01
  • Accepted : 2014.02.13
  • Published : 2014.03.31
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Abstract

Cisplatin is one of the most potent chemotherapy agents. However, its use is limited due to its toxicity in normal tissues, including the kidney and ear. In particular, nephrotoxicity induced by cisplatin is closely associated with oxidative stress and inflammation. Heme oxygenase-1(HO-1), the rate-limiting enzyme in the heme metabolism, has been implicated in a various cellular processes, such as inflammatory injury and anti-oxidant/oxidant homeostasis. Capsaicin is reported to have therapeutic potential in cisplatin-induced renal failures. However, the mechanisms underlying its protective effects on cisplatin-induced nephrotoxicity remain largely unknown. Herein, we demonstrated that administration of capsaicin ameliorates cisplatin-induced renal dysfunction by assessing the levels of serum creatinine and blood urea nitrogen (BUN) as well as tissue histology. In addition, capsaicin treatment attenuates the expression of inflammatory mediators and oxidative stress markers for renal damage. We also found that capsaicin induces HO-1 expression in kidney tissues and HK-2 cells. Notably, the protective effects of capsaicin were completely abrogated by treatment with either the HO inhibitor ZnPP IX or HO-1 knockdown in HK-2 cells. These results suggest that capsaicin has protective effects against cisplatin-induced renal dysfunction through induction of HO-1 as well as inhibition oxidative stress and inflammation.

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References

  1. Agarwal, A., Balla, J., Alam, J., Croatt, A.J., and Nath, K.A. (1995). Induction of heme oxygenase in toxic renal injury: a protective role in cisplatin nephrotoxicity in the rat. Kidney Int. 48, 1298-1307. https://doi.org/10.1038/ki.1995.414
  2. Arany, I., and Safirstein, R.L. (2003). Cisplatin nephrotoxicity. Semin. Nephrol. 23, 460-464. https://doi.org/10.1016/S0270-9295(03)00089-5
  3. Caterina, M.J., Schumacher, M.A., Tominaga, M., Rosen, T.A., Levine, J.D., and Julius, D. (1997). The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389, 816-824. https://doi.org/10.1038/39807
  4. Cenedeze, M.A., Goncalves, G.M., Feitoza, C.Q., Wang, P.M., Damiao, M.J., Bertocchi, A.P., Pacheco-Silva, A., and Camara, N.O. (2007). The role of toll-like receptor 4 in cisplatin-induced renal injury. Transplant Proc. 39, 409-411. https://doi.org/10.1016/j.transproceed.2007.01.032
  5. Chen, Q., Fischer, A., Reagan, J.D., Yan, L.J., and Ames, B.N. (1995). Oxidative DNA damage and senescence of human diploid fibroblast cells. Proc. Natl. Acad. Sci. USA 92, 4337-4341. https://doi.org/10.1073/pnas.92.10.4337
  6. Cohen, S.M., and Lippard, S.J. (2001). Cisplatin: from DNA damage to cancer chemotherapy. Prog. Nucleic Acid Res. Mol. Biol. 67, 93-130. https://doi.org/10.1016/S0079-6603(01)67026-0
  7. Hartsfield, C.L., Alam, J., and Choi, A.M. (1999). Differential signaling pathways of HO-1 gene expression in pulmonary and systemic vascular cells. Am. J. Physiol. 277, L1133-1141.
  8. Huang, S.P., Chen, J.C., Wu, C.C., Chen, C.T., Tang, N.Y., Ho, Y.T., Lo, C., Lin, J.P., Chung, J.G., and Lin, J.G. (2009). Capsaicin-induced apoptosis in human hepatoma HepG2 cells. Anticancer Res. 29, 165-174.
  9. Joe, B., and Lokesh, B.R. (1994). Role of capsaicin, curcumin and dietary n-3 fatty acids in lowering the generation of reactive oxygen species in rat peritoneal macrophages. Biochim. Biophys. Acta 1224, 255-263. https://doi.org/10.1016/0167-4889(94)90198-8
  10. Joung, E.J., Li, M.H., Lee, H.G., Somparn, N., Jung, Y.S., Na, H.K., Kim, S.H., Cha, Y.N., and Surh, Y.J. (2007). Capsaicin induces heme oxygenase-1 expression in HepG2 cells via activation of PI3K-Nrf2 signaling: NAD(P)H:quinone oxidoreductase as a potential target. Antioxid. Redox Signal. 9, 2087-2098. https://doi.org/10.1089/ars.2007.1827
  11. Kogure, K., Goto, S., Nishimura, M., Yasumoto, M., Abe, K., Ohiwa, C., Sassa, H., Kusumi, T., and Terada, H. (2002). Mechanism of potent antiperoxidative effect of capsaicin. Biochim. Biophys. Acta 1573, 84-92. https://doi.org/10.1016/S0304-4165(02)00335-5
  12. Kuhad, A., Pilkhwal, S., Sharma, S., Tirkey, N., and Chopra, K. (2007). Effect of curcumin on inflammation and oxidative stress in cisplatin-induced experimental nephrotoxicity. J. Agric. Food Chem. 55, 10150-10155. https://doi.org/10.1021/jf0723965
  13. Kuriakose, G.C., and Kurup, M.G. (2008). Evaluation of renoprotective effect of Aphanizomenon flos-aquae on cisplatin-induced renal dysfunction in rats. Ren. Fail. 30, 717-725. https://doi.org/10.1080/08860220802134730
  14. Lee, P.J., Camhi, S.L., Chin, B.Y., Alam, J., and Choi, A.M. (2000). AP-1 and STAT mediate hyperoxia-induced gene transcription of heme oxygenase-1. Am. J. Physiol. Lung Cell Mol. Physiol. 279, L175-182. https://doi.org/10.1152/ajplung.2000.279.1.L175
  15. Luke, D.R., Vadiei, K., and Lopez-Berestein, G. (1992). Role of vascular congestion in cisplatin-induced acute renal failure in the rat. Nephrol. Dial. Transplant. 7, 1-7.
  16. Maheshwari, R.A., Sailor, G.U., Patel, L., and Balaraman, R. (2013). Amelioration of cisplatin-induced nephrotoxicity by statins. Indian J. Pharmacol. 45, 354-358. https://doi.org/10.4103/0253-7613.115016
  17. Maines, M.D. (1988). Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications. FASEB. J. 2, 2557-2568. https://doi.org/10.1096/fasebj.2.10.3290025
  18. Mitazaki, S., Hashimoto, M., Matsuhashi, Y., Honma, S., Suto, M., Kato, N., Nakagawasai, O., Tan-No, K., Hiraiwa, K., Yoshida, M., et al. (2013). Interleukin-6 modulates oxidative stress produced during the development of cisplatin nephrotoxicity. Life Sci. 92, 694-700. https://doi.org/10.1016/j.lfs.2013.01.026
  19. Mukhopadhyay, P., Rajesh, M., Pan, H., Patel, V., Mukhopadhyay, B., Batkai, S., Gao, B., Hasko, G., and Pacher, P. (2010). Cannabinoid-2 receptor limits inflammation, oxidative/nitrosative stress, and cell death in nephropathy. Free Radic. Biol. Med. 48, 457-467. https://doi.org/10.1016/j.freeradbiomed.2009.11.022
  20. Mukhopadhyay, P., Horvath, B., Kechrid, M., Tanchian, G., Rajesh, M., Naura, A.S., Boulares, A.H., and Pacher, P. (2011). Poly(ADPribose) polymerase-1 is a key mediator of cisplatin-induced kidney inflammation and injury. Free Radic. Biol. Med. 51, 1774-1788. https://doi.org/10.1016/j.freeradbiomed.2011.08.006
  21. Nath, K.A., Haggard, J.J., Croatt, A.J., Grande, J.P., Poss, K.D., and Alam, J. (2000). The indispensability of heme oxygenase-1 in protecting against acute heme protein-induced toxicity in vivo. Am. J. Pathol. 156, 1527-1535. https://doi.org/10.1016/S0002-9440(10)65024-9
  22. Okada, Y., and Okajima, H. (2001). Antioxidant effect of capsaicin on lipid peroxidation in homogeneous solution, micelle dispersions and liposomal membranes. Redox Rep. 6, 117-122. https://doi.org/10.1179/135100001101536120
  23. Owuor, E.D., and Kong, A.N. (2002). Antioxidants and oxidants regulated signal transduction pathways. Biochem. Pharmacol. 64, 765-770. https://doi.org/10.1016/S0006-2952(02)01137-1
  24. Oyama, Y., Hashiguchi, T., Taniguchi, N., Tancharoen, S., Uchimura, T., Biswas, K.K., Kawahara, K., Nitanda, T., Umekita, Y., Lotz, M., et al. (2010). High-mobility group box-1 protein promotes granulomatous nephritis in adenine-induced nephropathy. Lab. Invest. 90, 853-866. https://doi.org/10.1038/labinvest.2010.64
  25. Pabla, N., and Dong, Z. (2008). Cisplatin nephrotoxicity: mechanisms and renoprotective strategies. Kidney Int. 73, 994-1007. https://doi.org/10.1038/sj.ki.5002786
  26. Ramesh, G., and Reeves, W.B. (2002). TNF-alpha mediates chemokine and cytokine expression and renal injury in cisplatin nephrotoxicity. J. Clin. Invest. 110, 835-842. https://doi.org/10.1172/JCI200215606
  27. Sahu, B.D., Kuncha, M., Sindhura, G.J., and Sistla, R. (2013). Hesperidin attenuates cisplatin-induced acute renal injury by decreasing oxidative stress, inflammation and DNA damage. Phytomedicine 20, 453-460. https://doi.org/10.1016/j.phymed.2012.12.001
  28. Sass, G., Barikbin, R., and Tiegs, G. (2012). The multiple functions of heme oxygenase-1 in the liver. Z. Gastroenterol. 50, 34-40. https://doi.org/10.1055/s-0031-1282046
  29. Shimeda, Y., Hirotani, Y., Akimoto, Y., Shindou, K., Ijiri, Y., Nishihori, T., and Tanaka, K. (2005). Protective effects of capsaicin against cisplatin-induced nephrotoxicity in rats. Biol. Pharm. Bull. 28, 1635-1638. https://doi.org/10.1248/bpb.28.1635
  30. Shiraishi, F., Curtis, L.M., Truong, L., Poss, K., Visner, G.A., Madsen, K., Nick, H.S., and Agarwal, A. (2000). Heme oxygenase-1 gene ablation or expression modulates cisplatin-induced renal tubular apoptosis. Am. J. Physiol. Renal Physiol. 278, F726-736. https://doi.org/10.1152/ajprenal.2000.278.5.F726
  31. Siddik, Z.H. (2003). Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene 22, 7265-7279. https://doi.org/10.1038/sj.onc.1206933
  32. So, H., Kim, H., Lee, J.H., Park, C., Kim, Y., Kim, E., Kim, J.K., Yun, K.J., Lee, K.M., Lee, H.Y., et al. (2007). Cisplatin cytotoxicity of auditory cells requires secretions of proinflammatory cytokines via activation of ERK and NF-kappaB. J. Assoc. Res. Otolaryngol. 8, 338-355. https://doi.org/10.1007/s10162-007-0084-9
  33. So, H., Kim, H., Kim, Y., Kim, E., Pae, H.O., Chung, H.T., Kim, H.J., Kwon, K.B., Lee, K.M., Lee, H.Y., et al. (2008). Evidence that cisplatin-induced auditory damage is attenuated by downregulation of pro-inflammatory cytokines via Nrf2/HO-1. J. Assoc. Res. Otolaryngol. 9, 290-306. https://doi.org/10.1007/s10162-008-0126-y
  34. Szallasi, A., and Blumberg, P.M. (1999). Vanilloid (Capsaicin) receptors and mechanisms. Pharmacol. Rev. 51, 159-212.
  35. Wang, D., and Lippard, S.J. (2005). Cellular processing of platinum anticancer drugs. Nat. Rev. Drug Discov. 4, 307-320. https://doi.org/10.1038/nrd1691
  36. Zhang, J., Nagasaki, M., Tanaka, Y., and Morikawa, S. (2003). Capsaicin inhibits growth of adult T-cell leukemia cells. Leuk. Res. 27, 275-283. https://doi.org/10.1016/S0145-2126(02)00164-9
  37. Zhang, B., Ramesh, G., Uematsu, S., Akira, S., and Reeves, W.B. (2008). TLR4 signaling mediates inflammation and tissue injury in nephrotoxicity. J. Am. Soc. Nephrol. 19, 923-932. https://doi.org/10.1681/ASN.2007090982

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