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SELENYUM SİKLOFOSFAMİD NEDENLİ HEPATOTOKSİSİTEYİ İYİLEŞTİREBİLİR

Year 2016, Volume: 38 Issue: 3, 34 - 39, 20.05.2016

Abstract

ÖZET: Siklofosfamid (CP)’in antitümör
etkinliği dozu ile doğru orantılıdır. Bununla birlikte, yüksek dozlarda yaygın
sitotoksisitelere neden olur. Selenyum (Se) yapısına katıldığı glutatyon
peroksidaz gibi selenoproteinler yoluyla potansiyel besinsel bir antioksidan
olarak biyolojik etkiler göstermektedir. Bu nedenle siklofosfamid nedenli
hepatotoksisitede selenyumun olası koruyucu etkisinin araştırılması
amaçlanmıştır. Toplam 42 adet erkek Spraque-Dawley sıçan 6 gruba (n=7) ayrıldı
(kontrol, 150 mg/kg CP, 0.5 ve 1 mg/kg Se, CP+0.5 ve CP+1 mg/kg Se grupları).
Se’un karaciğer toksisitesinde koruyucu etkisini belirlemek için serum alanin
transaminaz (ALT), aspartat transaminaz (AST), alkalen fosfataz (ALP) ve laktat
dehidrogenaz (LDH) seviyeleri belirlendi. Ayrıca karaciğer dokusu histolojik olarak
da incelendi. CP uygulanan grupta serum ALT (%145), AST (%226), ALP (%88), ve
LDH (%73) düzeyleri arttı. CP ile birlikte Se uygulanan gruplarda ALT, AST, ALP
ve LDH düzeyleri azaldı (p<0.05). Histolojik incelemelerde de CP+Se
gruplarında karaciğer doku hasarı önemli düzeyde azaldı. Sonuçlarımız
selenyumun antioksidan etkilerinin olduğu ve siklofosfamid nedenli oksidatif
hasarı ve çoklu organ toksisitelerini gidermede yararlı olabileceğini
göstermiştir.

ANAHTAR KELİMELER: Siklofosfamid, oksidatif stres, hepatotoksisite,
selenyum, rat.

SELENIUM AMELIORATES
CYCLOPHOSPHAMIDE-INDUCED HEPATOTOXICITY

ABSTRACT: The antitumoral efficieny of CP is
directly proportional to its administrated dose. However, high doses have a
tendency to result in generalized cytotoxicity. Selenium (Se) is a potent
nutritional antioxidant that carries out biological effects by its
incorporation into selenoproteins, such as glutathione peroxidase. Therefore we
aimed to investigate the possible protective effect of Se on CP-induced hepatotoxicity.
A total of 42 male Spraque-Dawley rats were divided into 6 groups (n=7)
(control, 150 mg/kg CP, 0.5 or 1 mg/kg Se and CP+0.5 and CP+1 mg/kg Se groups).
In order to determine the protective effects of Se on liver toxicity, the
levels of serum alanine transaminase (ALT), aspartate transaminase (AST),
alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were determined.
Also, the liver tissues were analysed histologically. Serum ALT (%145), AST
(%226), ALP (%88), and LDH (%73) levels increased in CP administrated rats. In
groups where CP and Se were given together ALT, AST, ALP, and LDH levels
decreased (p<0.05). Histological
analysis of liver tissue showed that tissue damage was significantly lower in
CP+Se groups. Our results show that Se has antioxidant effects and that it may
be useful to eliminate CP related oxidative damage.









KEYWORDS: Cyclophosphamide, oxidative stress,
hepatotoxicity, selenium, rat.

References

  • 1. Cavalletti, E., Tofanetti, O., & Zunino, F. (1986). Comparison of reduced glutathione with 2-mercaptoethane sulfonate to prevent cyclophosphamide-induced urotoxicity. Cancer letters, 32(1), 1-6.
  • 2. Kumar, K. B. H., & Kuttan, R. (2005). Chemoprotective activity of an extract of Phyllanthus amarus against cyclophosphamide induced toxicity in mice.Phytomedicine, 12(6), 494-500.
  • 3. Kennedy, R., Groepper, D., Tagen, M., Christensen, R., Navid, F., Gajjar, A., & Stewart, C. F. (2010). Stability of cyclophosphamide in extemporaneous oral suspensions. Annals of Pharmacotherapy, 44(2), 295-301.
  • 4. Abraham, P., & Rabi, S. (2011). Protective effect of aminoguanidine against cyclophosphamide-induced oxidative stress and renal damage in rats. Redox Report, 16(1), 8-14.
  • 5. Rang HP, Dale MM, Ritter JM, Flower RJ, Henderson G (2012) Rang, and Dale’s pharmacology. New York. 673-688.
  • 6. Sakthivel, K. M., & Guruvayoorappan, C. (2015). Acacia ferruginea inhibits cyclophosphamide-induced immunosuppression and urotoxicity by modulating cytokines in mice. Journal of immunotoxicology, 12(2), 154-163.
  • 7. Stankiewicz, A., Skrzydlewska, E., & Makiela, M. (2002). Effects of amifostine on liver oxidative stress caused by cyclophosphamide administration to rats.Drug metabolism and drug interactions, 19(2), 67-82.
  • 8. Senthilkumar, S., Devaki, T., Manohar, B. M., & Babu, M. S. (2006). Effect of squalene on cyclophosphamide-induced toxicity. Clinica Chimica Acta, 364(1), 335-342.
  • 9. Yang, Z., Faustino, P. J., Andrews, P. A., Monastra, R., Rasmussen, A. A., Ellison, C. D., & Cullen, K. J. (2000). Decreased cisplatin/DNA adduct formation is associated with cisplatin resistance in human head and neck cancer cell lines. Cancer chemotherapy and pharmacology, 46(4), 255-262.
  • 10. Hatfield, D. L., Tsuji, P. A., Carlson, B. A., & Gladyshev, V. N. (2014). Selenium and selenocysteine: roles in cancer, health, and development. Trends in biochemical sciences, 39(3), 112-120.
  • 11. Ayhanci, A., Yaman, S., Appak, S., & Gunes, S. (2009). Hematoprotective effect of seleno-L-methionine on cyclophosphamide toxicity in rats. Drug and chemical toxicology, 32(4), 424-428.
  • 12. Abraham, P., & Isaac, B. (2011). Ultrastructural changes in the rat kidney after single dose of cyclophosphamide—possible roles for peroxisome proliferation and lysosomal dysfunction in cyclophosphamide-induced renal damage. Human & experimental toxicology, 30(12), 1924-1930.
Year 2016, Volume: 38 Issue: 3, 34 - 39, 20.05.2016

Abstract

References

  • 1. Cavalletti, E., Tofanetti, O., & Zunino, F. (1986). Comparison of reduced glutathione with 2-mercaptoethane sulfonate to prevent cyclophosphamide-induced urotoxicity. Cancer letters, 32(1), 1-6.
  • 2. Kumar, K. B. H., & Kuttan, R. (2005). Chemoprotective activity of an extract of Phyllanthus amarus against cyclophosphamide induced toxicity in mice.Phytomedicine, 12(6), 494-500.
  • 3. Kennedy, R., Groepper, D., Tagen, M., Christensen, R., Navid, F., Gajjar, A., & Stewart, C. F. (2010). Stability of cyclophosphamide in extemporaneous oral suspensions. Annals of Pharmacotherapy, 44(2), 295-301.
  • 4. Abraham, P., & Rabi, S. (2011). Protective effect of aminoguanidine against cyclophosphamide-induced oxidative stress and renal damage in rats. Redox Report, 16(1), 8-14.
  • 5. Rang HP, Dale MM, Ritter JM, Flower RJ, Henderson G (2012) Rang, and Dale’s pharmacology. New York. 673-688.
  • 6. Sakthivel, K. M., & Guruvayoorappan, C. (2015). Acacia ferruginea inhibits cyclophosphamide-induced immunosuppression and urotoxicity by modulating cytokines in mice. Journal of immunotoxicology, 12(2), 154-163.
  • 7. Stankiewicz, A., Skrzydlewska, E., & Makiela, M. (2002). Effects of amifostine on liver oxidative stress caused by cyclophosphamide administration to rats.Drug metabolism and drug interactions, 19(2), 67-82.
  • 8. Senthilkumar, S., Devaki, T., Manohar, B. M., & Babu, M. S. (2006). Effect of squalene on cyclophosphamide-induced toxicity. Clinica Chimica Acta, 364(1), 335-342.
  • 9. Yang, Z., Faustino, P. J., Andrews, P. A., Monastra, R., Rasmussen, A. A., Ellison, C. D., & Cullen, K. J. (2000). Decreased cisplatin/DNA adduct formation is associated with cisplatin resistance in human head and neck cancer cell lines. Cancer chemotherapy and pharmacology, 46(4), 255-262.
  • 10. Hatfield, D. L., Tsuji, P. A., Carlson, B. A., & Gladyshev, V. N. (2014). Selenium and selenocysteine: roles in cancer, health, and development. Trends in biochemical sciences, 39(3), 112-120.
  • 11. Ayhanci, A., Yaman, S., Appak, S., & Gunes, S. (2009). Hematoprotective effect of seleno-L-methionine on cyclophosphamide toxicity in rats. Drug and chemical toxicology, 32(4), 424-428.
  • 12. Abraham, P., & Isaac, B. (2011). Ultrastructural changes in the rat kidney after single dose of cyclophosphamide—possible roles for peroxisome proliferation and lysosomal dysfunction in cyclophosphamide-induced renal damage. Human & experimental toxicology, 30(12), 1924-1930.
There are 12 citations in total.

Details

Subjects Health Care Administration
Journal Section ORİJİNAL MAKALE
Authors

Adnan Ayhancı This is me

Özge Acar This is me

Varol Şahintürk This is me

Sibel Güneş

İlknur Kulcanay Şahin This is me

Ahmet Musmul This is me

Sema Uslu This is me

Publication Date May 20, 2016
Published in Issue Year 2016 Volume: 38 Issue: 3

Cite

Vancouver Ayhancı A, Acar Ö, Şahintürk V, Güneş S, Kulcanay Şahin İ, Musmul A, Uslu S. SELENYUM SİKLOFOSFAMİD NEDENLİ HEPATOTOKSİSİTEYİ İYİLEŞTİREBİLİR. Osmangazi Tıp Dergisi. 2016;38(3):34-9.


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