Archives of Dermatological Research

, Volume 304, Issue 6, pp 451–457 | Cite as

Role of cellular oxidative stress and cytochrome c in the pathogenesis of psoriasis

  • Sami A. Gabr
  • Ahmad H. Al-Ghadir
Original Paper


Oxidative-free radicals and apoptosis have linked to chronic skin diseases. Higher levels of oxidative radicals and the release of mitochondrial cytochrome c may have a role in the pathogenesis of psoriasis. We investigated the possible role of cellular oxidative stress and release of cytochrome c of mitochondria in the pathogenesis of psoriasis. Disease severity was assessed by psoriasis area severity index score (PASI) of 55 psoriasis patients, they grouped as mild (11), moderate (20) and severe (24), also 20 healthy individuals used as controls. All groups were subjected for serum malondialdehyde (MDA), nitric oxide (NO·), superoxide dismutase (SOD), catalase (CAT), total antioxidant status (TAS) and serum cytochrome c concentrations. We found that, (1) Severity wise increase in MDA and NO·, and decrease in SOD, CAT and TAS levels in all patients with different degrees of psoriasis; (2) PASI showed positive correlation with the increase in MDA and NO·, and negatively with decreased SOD, CAT and TAS levels; (3) significant increase in cytochrome c level was observed among psoriasis patients which showed negative correlation to MDA and NO· levels in mild and positively with moderate and severe groups. The release of mitochondrial cytochrome c indicates the induction of apoptosis mediated via oxidative stress which ultimately plays role in the pathogenesis of psoriasis.


Mitochondria Psoriasis PASI score Apoptosis cytochrome c Oxidative stress Antioxidant status Antioxidant enzymes 


Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Baz K, Cimen MYB, Kokturk A et al (2003) Oxidant/antioxidant status in patients with psoriasis. Yonsei Med J 44(6):987–990PubMedGoogle Scholar
  2. 2.
    Bickers DR, Athar M (2006) Oxidative stress in the pathogenesis of skin disease. J Investig Dermatol 126(12):2565–2575PubMedCrossRefGoogle Scholar
  3. 3.
    Briganti S, Picardo M (2003) Antioxidant activity, lipid peroxidation and skin diseases—what’s new? JEADV 17:663–669PubMedGoogle Scholar
  4. 4.
    Chen Q, Chai YC, Mazumder S et al (2003) The late increase in intracellular free radical oxygen species during apoptosis is associated with cytochrome c release, caspase activation, and mitochondrial dysfunction. Cell Death Differ 10(3):323–334PubMedCrossRefGoogle Scholar
  5. 5.
    Clancy RM, Amin AR, Abramson SB (1998) The role of nitric oxide in inflammation and immunity. Arthritis Rheum 41(7):1141–1151PubMedCrossRefGoogle Scholar
  6. 6.
    Corrocher R, Ferrari S, Gironcoli M et al (1989) Effect of fish oil supplementation on erythrocyte lipid pattern, malondialdehyde production and glutathione peroxidase activity in psoriasis. Clin Chim Acta 179:121–132PubMedCrossRefGoogle Scholar
  7. 7.
    Cortas NK, Wakid NW (1990) Determination of inorganic nitrate in serum and urine by a kinetic cadmium reduction method. Clin Chem 36(8):1440–1443PubMedGoogle Scholar
  8. 8.
    Danial NN, Korsmeyer SJ (2004) Cell death: critical control points. Cell 116:205–219PubMedCrossRefGoogle Scholar
  9. 9.
    Deepak R, Douglas EB, Douglas G (2006) Keratinocyte apoptosis in epidermal development and disease. J Invest Dermatol 126(2):243–257CrossRefGoogle Scholar
  10. 10.
    Dimon GS, Gerbaud P, Therond P et al (2000) Increased oxidative damage to fibroblasts in skin with and without lesions in psoriasis. J Investig Dermatol 114:984–989CrossRefGoogle Scholar
  11. 11.
    Ferretti G, Bacchetti T, Campanati A, Simonetti O, Liberati G, Offidani A (2012) Correlation between lipoprotein(a) and lipid peroxidation in psoriasis: role of the enzyme paraoxonase-1. Br J Dermatol 166(1):204–207PubMedCrossRefGoogle Scholar
  12. 12.
    Gokhale NR, Belgaumkar VA, Pandit DP, Deshpande S, Damle DKA (2005) Study of serum nitric oxide level in psoriasis. Indian J Dermatol Venereol Leprol 71:175–178PubMedCrossRefGoogle Scholar
  13. 13.
    Gornicki A, Gutsze A (2001) Erythrocyte membrane fluidity changes in psoriasis: an EPR study. J Dermatol Sci 27:27–30PubMedCrossRefGoogle Scholar
  14. 14.
    Goth L (1991) A simple method for determination of serum catalase activity and revision of reference range. Clin Chim Acta 196:143–152PubMedCrossRefGoogle Scholar
  15. 15.
    Green DR, Kroemer G (2004) The pathophysiology of mitochondrial cell death. Science 305:626–629PubMedCrossRefGoogle Scholar
  16. 16.
    Hortelano S, Alvarez AM, Bosca L (1999) Nitric oxide induces tyrosine nitration, and release of cytochrome c preceding an increase of mitochondrial transmembrane potential in macrophages. FASEB J. 13:2311–2317PubMedGoogle Scholar
  17. 17.
    Jacobson MD (1996) Reactive oxygen species and programmed cell death. Trends Biochem Sci 21:83–86PubMedGoogle Scholar
  18. 18.
    Kadam DP, Suryakar AN, Ankush RD, Kadam CY, Deshpande KH (2010) Role of oxidative stress in various stages of psoriasis. Indian J Clin Biochem 25(4):388–392PubMedCrossRefGoogle Scholar
  19. 19.
    Kampa M, Nistikaki A, Tsaousis V, Maliaraki N, Notas G, Gastonas EA (2002) New automated method for the determination of TAC of human plasma based on crocin bleaching assay. BMC Clinical Pathol 2:3–21CrossRefGoogle Scholar
  20. 20.
    Karaarslan IK, Girgin SF, Ertam I, Alper S, Ozturk G, Yildirim SE (2006) Broad-band ultraviolet B phototherapy is associated with elevated serum thiobarbituric acid reactive substance and nitrite-nitrate levels in psoriatic patients. J Eur Acad Dermatol Venereol 20(10):1226–1231CrossRefGoogle Scholar
  21. 21.
    Kolb BV, Fehsel K, Michel G, Ruzicka T (1994) Epidermal keratinocyte expression of inducible nitric oxide synthase in skin lesions of psoriasis vulgaris. Lancet 344:139CrossRefGoogle Scholar
  22. 22.
    Kroemer G, Galluzzi L, Brenner C (2007) Mitochondrial membrane permeabilization in cell death. Physiol Rev 87(1):16–99CrossRefGoogle Scholar
  23. 23.
    Laporte M, Galand P, Fokan D, de Graef C, Heenen M (2000) Apoptosis in established and healing psoriasis. Dermatology 200(4):314–316PubMedCrossRefGoogle Scholar
  24. 24.
    Lebwohl M (2003) Psoriasis. Lancet 361:1197–1204PubMedCrossRefGoogle Scholar
  25. 25.
    Lenaz G, Bovina C, Daurelio M et al (2002) Role of mitochondria in oxidative stress and aging. Ann N Y Acad Sci 959:199–213PubMedCrossRefGoogle Scholar
  26. 26.
    Li C, Zhou HM (2011) The role of manganese superoxide dismutase in inflammation defense. Enzyme Res 2011:387176PubMedGoogle Scholar
  27. 27.
    Li FL, Xu R, Zeng QC et al (2012) Tanshinone IIA inhibits growth of keratinocytes through cell cycle arrest and apoptosis: underlying treatment mechanism of psoriasis. Evid Based Complement Alternat Med 2012:927658PubMedGoogle Scholar
  28. 28.
    Louden BA, Pearce DJ, Lang W, Feldman SR (2004) A simplified psoriasis area severity index (SPASI) for rating psoriasis severity in clinical patients. Dermatol Online J 10(2):7PubMedGoogle Scholar
  29. 29.
    Lykkesfeldt J (2007) Malondialdehyde as biomarker of oxidative damage to lipids caused by smoking. Clin Chim Acta 380:50–58PubMedCrossRefGoogle Scholar
  30. 30.
    Mcgill A, Frank A, Emmett N, Turnbull DM, Birch MA, Reynolds NJ (2005) The anti-psoriatic drug anthralin accumulates in keratinocyte mitochondria, dissipates mitochondrial membrane potential, and induces apoptosis through a pathway dependent on respiratory competent mitochondria. FASEB J 19(8):1012–1014PubMedGoogle Scholar
  31. 31.
    Moshage H, Kok B, Huizenga JR, Jansen PLM (1995) Nitrite and nitrate determinations in plasma: a critical evaluation. Clin Chem 41:892–896PubMedGoogle Scholar
  32. 32.
    Orem A, Aliyazicioglu R, Kiran E, Vanizor B, Cimnocodeit G, Deger O (1997) The relationship between nitric oxide production and activity of the disease in patients with psoriasis. Arch Dermatol 133:1606–1607PubMedCrossRefGoogle Scholar
  33. 33.
    Ormerod AD, Weller R, Copeland P et al (1998) Detection of nitric oxide and nitric oxide synthases in psoriasis. Arch Dermatol Res 290:3–8PubMedCrossRefGoogle Scholar
  34. 34.
    Rashmi R, Rao KSJ, Basavaraj KH (2009) A comprehensive review of biomarkers in psoriasis. Clin Exp Dermatol 34:658–663PubMedCrossRefGoogle Scholar
  35. 35.
    Relhan V, Gupta SK, Dayal S, Pandey R, Lal H (2002) Blood thiols and malondialdehyde levels in psoriasis. J Dermatol 29:399–403PubMedGoogle Scholar
  36. 36.
    Robbins D, Zhao Y (2011) The role of manganese superoxide dismutase in skin cancer. Enzyme Res 2011:409295PubMedGoogle Scholar
  37. 37.
    Rocha PP, Santos SA, Rebelo I, Figueiredo A, Quantanilha A, Teixeira F (2001) Dyslipidemia and oxidative stress in mild and in severe psoriasis as a risk for cardiovascular disease. Clin Chim Acta 303:33–39CrossRefGoogle Scholar
  38. 38.
    Satoh K (1978) Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method. Clin Chim Acta 90:37–43PubMedCrossRefGoogle Scholar
  39. 39.
    Shilov VN, Sergienko VI (2000) Oxidative stress in keratinocytes as an etiopathogenetic factor of psoriasis. Bull Exp Biol Med 129:309–313PubMedCrossRefGoogle Scholar
  40. 40.
    Sikar AA, Ozdoğan HK, Bayramgürler D, Cekmen MB, Bilen N, Kıran R (2011) Nitric oxide and malondialdehyde levels in plasma and tissue of psoriasis patients. J Eur Acad Dermatol Venereol 1468–3083Google Scholar
  41. 41.
    Sirsjo A, Karlsson M, Gidof A, Rollman O, Torma H (1996) Increased expression of inducible nitric oxide synthase in psoriatic skin and cytokine-stimulated cultured keratinocytes. Br J Dermatol 134(4):643–648PubMedCrossRefGoogle Scholar
  42. 42.
    Sravani PV, Babu NK, Gopal KV, Rao GR, Rao AR, Moorthy B, Rao TR (2009) Determination of oxidative stress in vitiligo by measuring superoxide dismutase and catalase levels in vitiliginous and non-vitiliginous skin. Indian J Dermatol Venereol Leprol 3:268–271Google Scholar
  43. 43.
    Susin SA, Lorenzo HK, Zamzami N et al (1999) Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 397:441–446PubMedCrossRefGoogle Scholar
  44. 44.
    Taylor I, Megson I, Haslett C, Rossi AG (2003) Nitric oxide: a key regulator of myeloid inflammatory cell apoptosis. Cell Death Differ 10:418–430PubMedCrossRefGoogle Scholar
  45. 45.
    Tekin NS, Ilter N, Sancak B, Ozden MG, Gurer MA (2006) Nitric oxide levels in patients with psoriasis treated with methotrexate. Mediators Inflamm 2006(3):16043PubMedGoogle Scholar
  46. 46.
    Toker A, Kadi M, Yildirim AK, Aksoy H, Akçay F (2009) Serum lipid profile paraoxonase and arylesterase activities in psoriasis. Cell Biochem Funct 27(3):176–180PubMedCrossRefGoogle Scholar
  47. 47.
    Turner CP, Toye AM, Jones OT (1998) Keratinocyte superoxide generation. Free Radic Biol Med 24:401–407PubMedCrossRefGoogle Scholar
  48. 48.
    Vanizor KB, Orem A, Cimşit G, Yandi YE, Calapoglu M (2003) Evaluation of the atherogenic tendency of lipids and lipoprotein content and their relationships with oxidant–antioxidant system in patients with psoriasis. Clin Chim Acta 328(1–2):71–82CrossRefGoogle Scholar
  49. 49.
    Wang H, Peters T, Kess D et al (2006) Activated macrophages are essential in murine model for T-cell mediated chronic psoriasis form skin inflammation. J. Clin. Invest. 116:2105–2114PubMedCrossRefGoogle Scholar
  50. 50.
    Wenhua G, Yongmei P, Kathy QL, Donald CC (2001) Temporal relationship between cytochrome c release and mitochondrial swelling during UV-induced apoptosis in living HeLa cells. J Cell Sci 114:2855–2862Google Scholar
  51. 51.
    Yildirim M, Inaloz HS, Baysal V, Delibas N (2003) The role of oxidants and antioxidants in psoriasis. J Eur Acad Dermatol Venereol 17:34–36PubMedCrossRefGoogle Scholar
  52. 52.
    Zhou Q, Mrowietz U, Rostami-Yazdi M (2009) Oxidative stress in the pathogenesis of psoriasis. Free Radical Biol Med 47(7):891–905CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  1. 1.Department of Anatomy, Faculty of MedicineMansoura UniversityMansouraEgypt
  2. 2.Rehabilitation Research Chair (RRC)King Saud UniversityRiyadhSaudi Arabia
  3. 3.Department of Rehabilitation Science, College of Applied Medical SciencesKing Saud UniversityRiyadhSaudi Arabia

Personalised recommendations