Öz
Amaç: Son yıllarda zerdeçaldaki aktif polifenol olan kurkumininsisplatin içeren kemoterapi rejimlerinde sinerjistik bir role sahip olduğunu gösteren bilgiler artmaktadır. Kurkuminin güvenli bir adjuvan olduğunu göstermek için söz konusu ajanların sistemik etkileşimlerinin araştırılması gerektiğinden bu polifenolünsisplatin uygulanan sıçanlarda hipotalamik-hipofizer-adrenal HPA aksa etkilerinin incelemesi amaçlandı.Gereç ve Yöntem: Toplamda 34 erkek Wistar sıçan kontrol n=7 , sisplatin n=10 , kurkumin n=7 ve sisplatin + kurkumin n=10 olmak üzere dört gruba ayrıldı. Sisplatin ve kurkumin gruplarındaki sıçanlara 5 hafta süresince sırasıyla 5 mg/kg/hafta, i.p. sisplatin ve 300 mg/kg/gün, p.o. kurkumin uygulandı. Sisplatin + kurkumin grubu aynı dozlarda hem sisplatin hem kurkumin aldı. Kontrol grubuna yalnızca taşıyıcı fizyolojik salin ve mısır yağı verildi. Hayvanlar adrenokortikotropik hormon ACTH ve kortikosteron CORT ölçümleri için kan elde etmek maksadıyla eksanguine edildi. Beyin çıkarıldı ve hipokampal dokuda mineralokortikoid MR ve glukokortikoid GR reseptörleri belirlendi. Analizler ELISA yöntemiyle gerçekleştirildi.Bulgular: Sisplatin ve kurkumin tedavilerinin araştırılan parametreleri bozmadığını bulduk p>0.05 . Ayrıca, kurkumin ve sisplatinin birlikte uygulanmasının kontrollere kıyasla ACTH ve CORT’un plazma konsantrasyonları ile hipokampal MR ve GR seviyelerini değiştirmediğini gözlendi p>0.05 .Sonuç: Sonuçlarımıza göre tek başına veya kombine halde sisplatin ve kurkumin tedavisi HPA aksını etkilememektedir
Anahtar Kelimeler
sisplatin kurkumin hipotalamik-hipofizer-adrenal aks kortikosteroid reseptörleri
Kaynakça
- Lebwohl D, Canetta R. Clinical development of platinum complexes in cancer therapy: an historical perspective and an update. Eur J Cancer 1998;34:1522-34.
- Wang G, Reed E, Li QQ. Molecular basis of cellular respon- se to cisplatin chemotherapy in non-small cell lung cancer (Review). Oncology Reports 2004;12:955-65.
- Im GJ, Chang J, Lee S, Choi J, Jung HH, Lee HM, et al. Pro- tective role of edaravone against cisplatin-induced ototoxi- city in an auditory cell line. Hearing Res 2015;330:113-8.
- Jamshidzadeh A, Heidari R, Golzar T, Derakhshanfar A. Effect of Eisenia foetida Extract against Cisplatin-Induced Kidney Injury in Rats. J Diet Suppl 2016;13:551-9.
- Ateyya H, Yosef H, Nader MA. Ameliorative effect of tri- metazidine on cisplatin-induced hepatotoxicity in rats. Can J Physiol Pharmacol 2015;19:1-6.
- Oz M, Nurullahoglu Atalik KE, Yerlikaya FH, Demir EA. Curcumin alleviates cisplatin-induced learning and me- mory impairments. Neurobiol Learn Mem 2015;123:43-9.
- Yin HL, Wang YL, Li J F, et al. Effects of curcumin on hip- pocampal expression of NgR and axonal regeneration in Abeta-induced cognitive disorder rats. Genetics and mole- cular research : GMR. 2014;13:2039-47.
- Sandur SK, Pandey MK, Sung B, Ahn KS, Murakami A, Sethi G, et al. Curcumin, demethoxycurcumin, bisdemet- hoxycurcumin, tetrahydrocurcumin and turmerones diffe- rentially regulate anti-inflammatory and anti-proliferative responses through a ROS-independent mechanism. Carci- nogenesis. 2007;28:1765-73.
- Anand P, Sundaram C, Jhurani S, Kunnumakkara AB, Ag- garwal BB. Curcumin and cancer: an "old-age" disease with an "age-old" solution. Cancer Letters 2008;267:133-64.
- Waseem M, Pandey P, Tomar B, Raisuddin S, Parvez S. Ameliorative action of curcumin in cisplatin-mediated he- patotoxicity: an in vivo study in Wistar rats. Arch Med Res 2014;45:462-8.
- Sidhu GS, Mani H, Gaddipati JP, et al. Curcumin enhances wound healing in streptozotocin induced diabetic rats and genetically diabetic mice. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society 1999;7:362-74.
- Wang Z, Zhang Q, Yuan L, et al. The effects of curcumin on depressive-like behavior in mice after lipopolysaccharide administration. Behav Brain Res 2014;274:282-90.
- Imbaby S, Ewais M, Essawy S, Farag N. Cardioprotective ef- fects of curcumin and nebivolol against doxorubicin-indu- ced cardiac toxicity in rats. Hum Exp Toxicol 2014;33:800- 13.
- Mishra S, Palanivelu K. The effect of curcumin (turmeric) on Alzheimer's disease: An overview. Ann Indian Acad Neurol 2008;11:13-9.
- Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. The Journal of biological chemistry. 1951;193:265-75.
- Erken HA, Koc ER, Yazici H, Yay A, Onder GO, Sarici SF. Selenium partially prevents cisplatin-induced neurotoxi- city: a preliminary study. Neurotoxicology 2014;42:71-5.
- Ugur S, Ulu R, Dogukan A, Gurel A, Yigit IP, Gozel N, et al. The renoprotective effect of curcumin in cisplatin-induced nephrotoxicity. Renal Failure 2015;37:332-6.
- Ehlert U, Gaab J, Heinrichs M. Psychoneuroendocrinologi- cal contributions to the etiology of depression, posttrauma- tic stress disorder, and stress-related bodily disorders: the role of the hypothalamus-pituitary-adrenal axis. Biological Psychology 2001;57:141-52.
- Weaver IC, La Plante P, Weaver S, et al. Early environ- mental regulation of hippocampal glucocorticoid receptor gene expression: characterization of intracellular mediators and potential genomic target sites. Mol Cell Endocrinol 2001;185:205-18.
- de Kloet ER, Joels M, Holsboer F. Stress and the brain: from adaptation to disease. Nature reviews Neuroscience 2005;6:463-75.
- Kellendonk C, Gass P, Kretz O, Schutz G, Tronche F. Cor- ticosteroid receptors in the brain: gene targeting studies. Brain Res Bull 2002;57:73-83.
- van Haarst AD, Oitzl MS, de Kloet ER. Facilitation of feed- back inhibition through blockade of glucocorticoid recep- tors in the hippocampus. Neurocheem Res 1997;22:1323-8.
Öz
Objective: There are recently growing evidences as to the synergistic role of curcumin, the active polyphenol of turmeric, in cisplatin containing chemotherapy regimens. The effects of this polyphenol on the hypothalamic-pituitary-adrenal HPA axis in cisplatin-treated rats were investigated to figure out systemic interactions of the mentioned agents which is necessary in order to ascertain the safety of curcumin as an adjuvant.Material and Methods: A total of 34 male Wistar rats were divided into four groups as control n=7 , curcumin n=10 , and cisplatin + curcumin n=10 . Respectively, 5 mg/kg/week, i.p. cisplatin or 300 mg/kg/day, p.o.curcumin was administered for 5 weeks to the rats in cisplatin and curcumin groups. The cisplatin + curcumin group received both cisplatin and curcumin in same doses. Only vehicle physiological saline and corn oil was given to the control group. The animals were exsanguinated to obtain blood for adrenocorticotropic hormone ACTH and corticosterone CORT measurements. The brains were excised and hippocampal mineralocorticoid MR and glucocorticoid receptors GR receptors were estimated. The analyses were conducted by the ELISA method.Results: We found that the cisplatin and curcumin treatments did not alter the investigated parameters p>0.05 . Also, we observed that the co-administration of curcumin and cisplatin did not change the plasma concentrations of ACTH and CORT as well as the levels of hippocampal MR and GR as compared to the controls p>0.05 .Conclusion: To our results, singly or combined cisplatin and curcumin treatments do not influence the HPA axis
Anahtar Kelimeler
cisplatin curcumin hypothalamic-pituitary-adrenal axis corticosteroid receptors
Kaynakça
- Lebwohl D, Canetta R. Clinical development of platinum complexes in cancer therapy: an historical perspective and an update. Eur J Cancer 1998;34:1522-34.
- Wang G, Reed E, Li QQ. Molecular basis of cellular respon- se to cisplatin chemotherapy in non-small cell lung cancer (Review). Oncology Reports 2004;12:955-65.
- Im GJ, Chang J, Lee S, Choi J, Jung HH, Lee HM, et al. Pro- tective role of edaravone against cisplatin-induced ototoxi- city in an auditory cell line. Hearing Res 2015;330:113-8.
- Jamshidzadeh A, Heidari R, Golzar T, Derakhshanfar A. Effect of Eisenia foetida Extract against Cisplatin-Induced Kidney Injury in Rats. J Diet Suppl 2016;13:551-9.
- Ateyya H, Yosef H, Nader MA. Ameliorative effect of tri- metazidine on cisplatin-induced hepatotoxicity in rats. Can J Physiol Pharmacol 2015;19:1-6.
- Oz M, Nurullahoglu Atalik KE, Yerlikaya FH, Demir EA. Curcumin alleviates cisplatin-induced learning and me- mory impairments. Neurobiol Learn Mem 2015;123:43-9.
- Yin HL, Wang YL, Li J F, et al. Effects of curcumin on hip- pocampal expression of NgR and axonal regeneration in Abeta-induced cognitive disorder rats. Genetics and mole- cular research : GMR. 2014;13:2039-47.
- Sandur SK, Pandey MK, Sung B, Ahn KS, Murakami A, Sethi G, et al. Curcumin, demethoxycurcumin, bisdemet- hoxycurcumin, tetrahydrocurcumin and turmerones diffe- rentially regulate anti-inflammatory and anti-proliferative responses through a ROS-independent mechanism. Carci- nogenesis. 2007;28:1765-73.
- Anand P, Sundaram C, Jhurani S, Kunnumakkara AB, Ag- garwal BB. Curcumin and cancer: an "old-age" disease with an "age-old" solution. Cancer Letters 2008;267:133-64.
- Waseem M, Pandey P, Tomar B, Raisuddin S, Parvez S. Ameliorative action of curcumin in cisplatin-mediated he- patotoxicity: an in vivo study in Wistar rats. Arch Med Res 2014;45:462-8.
- Sidhu GS, Mani H, Gaddipati JP, et al. Curcumin enhances wound healing in streptozotocin induced diabetic rats and genetically diabetic mice. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society 1999;7:362-74.
- Wang Z, Zhang Q, Yuan L, et al. The effects of curcumin on depressive-like behavior in mice after lipopolysaccharide administration. Behav Brain Res 2014;274:282-90.
- Imbaby S, Ewais M, Essawy S, Farag N. Cardioprotective ef- fects of curcumin and nebivolol against doxorubicin-indu- ced cardiac toxicity in rats. Hum Exp Toxicol 2014;33:800- 13.
- Mishra S, Palanivelu K. The effect of curcumin (turmeric) on Alzheimer's disease: An overview. Ann Indian Acad Neurol 2008;11:13-9.
- Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. The Journal of biological chemistry. 1951;193:265-75.
- Erken HA, Koc ER, Yazici H, Yay A, Onder GO, Sarici SF. Selenium partially prevents cisplatin-induced neurotoxi- city: a preliminary study. Neurotoxicology 2014;42:71-5.
- Ugur S, Ulu R, Dogukan A, Gurel A, Yigit IP, Gozel N, et al. The renoprotective effect of curcumin in cisplatin-induced nephrotoxicity. Renal Failure 2015;37:332-6.
- Ehlert U, Gaab J, Heinrichs M. Psychoneuroendocrinologi- cal contributions to the etiology of depression, posttrauma- tic stress disorder, and stress-related bodily disorders: the role of the hypothalamus-pituitary-adrenal axis. Biological Psychology 2001;57:141-52.
- Weaver IC, La Plante P, Weaver S, et al. Early environ- mental regulation of hippocampal glucocorticoid receptor gene expression: characterization of intracellular mediators and potential genomic target sites. Mol Cell Endocrinol 2001;185:205-18.
- de Kloet ER, Joels M, Holsboer F. Stress and the brain: from adaptation to disease. Nature reviews Neuroscience 2005;6:463-75.
- Kellendonk C, Gass P, Kretz O, Schutz G, Tronche F. Cor- ticosteroid receptors in the brain: gene targeting studies. Brain Res Bull 2002;57:73-83.
- van Haarst AD, Oitzl MS, de Kloet ER. Facilitation of feed- back inhibition through blockade of glucocorticoid recep- tors in the hippocampus. Neurocheem Res 1997;22:1323-8.
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Bölüm | Original Article |
| Yazarlar | |
| Yayımlanma Tarihi | 1 Mart 2017 |
| Yayımlandığı Sayı | Yıl 2017 Cilt: 27 Sayı: 1 |
Genel Tıp Dergisi Creative Commons Atıf-GayriTicari 4.0 Uluslararası Lisansı (CC BY NC) ile lisanslanmıştır.