Kronik Stres ve Böbrek: Sıçan Modeli Üzerinde Morfometrik ve Histopatolojik Çalışma

Year 2017, Volume: 7 Issue: 4, 168 - 175, 04.01.2018

Elvan Şahin Tuba Demirci , Semin Gedikli

https://doi.org/10.31832/smj.366673

Abstract

Amaç: Günlük yaşamın bir parçası haline gelen stres, vücudun dengesini bozarak
pek çok hastalığa neden olur. Biz de bu çalışmada, kronik strese sebep olan
faktörlere maruz kalındığında böbrekte meydana gelebilecek olası yapısal
değişiklikleri araştırmayı amaçladık.

Gereç ve Yöntem: Bu çalışmada 12 adet Sprague Dawley cinsi yetişkin erkek sıçan
kullanıldı. Sıçanlar rastgele kontrol (n=6) ve stres (n=6) grubu olarak ikiye
ayrıldıktan sonra, stres grubundakilere 4 hafta boyunca “beklenmedik kronik
hafif stres” protokolü uygulandı. Deneyin sonunda anestezisi altında feda
edilen bütün sıçanların böbrekleri çıkarıldı ve derhal “suya daldırma yöntemi”
ile hacimleri ölçüldü. Böbrekler rutin histolojik işlemleri takiben,
histopatolojik değerlendirme için ışık mikroskobunda incelendi.

Bulgular: Stres grubundaki sıçanların böbrek hacimlerinin (0,90 ± 0,096 ml)
kontrol grubundakilerin böbrek hacimlerine (1,075 ± 0,106 ml) kıyasla önemli
düzeyde azalmış olduğu (p<0,05;
independent samples t test)  tespit
edildi. Stres grubu böbreklerinin ışık mikroskobik değerlendirmesinde, nefron
tübüllerinin epitelinde nekrotik dejenerasyon ve dökülmeler saptandı. Proksimal
ve distal tübüllerin epitelinde, yer yer hücresel parçalanma ve tübül duvar
bütünlüğünün bozulması ile sonuçlanan sitoplazmik şişme ve hücresel
vakuolleşmeler belirgindi. Henle kulpunda da lümende bariz dilatasyonlar ve
epitelde nekrotik değişiklikler tespit edildi. İlaveten glomerüllerde büzüşme
ve Bowman boşluğunda genişlemeler gözlendi.

Sonuç: Elde edilen bulgulara dayanarak, kronik stresin böbrekte büyük olasılıkla
fonksiyonel yetersizliğe yol açacak glomerüler hasara ve tübül epitel
hücrelerinde zedelenmeye sebep olduğu düşünüldü.

Keywords

Kronik stres, böbrek, sıçan, histopatoloji, renal hasar, nefron tübülü

References

• Diane A, Victoriano M, Fromentin G, Tome D, Larue-Achagiotis C. Acute stress modifies food choice in Wistar male and female rats. Appetite 2008;50:397-407.
• Balcioglu I, Savrun M. Stress and Hormones. T Klin J Psychiatry 2001;2:43-50.
• Silberman DM, Wald MR, Genaro AM. Acute and chronic stress exert opposing effects on antibody responses associated with changes in stress hormone regulation of T-lymphocyte reactivity. J Neuroimmunol 2003;144:53-60.
• Epel ES, Blackburn EH, Lin J, Dhabhar FS, Adler NE, Morrow JD et al. Accelerated telomere shortening in response to life stress. Proc Natl Acad Sci U S A 2004;101:17312-17315.
• Gulati K, Chakraborti A, Ray A. Gender Based Differences in Stress-induced Gastric Ulcer Formation and its Regulation by Nitric Oxide (NO): An Experimental Study. Curr Pharm Design 2015;21:3395-3401.
• Derian W, Soundarraj D, Rosenberg M. Stress-induced cardiomyopathy: Not always apical ballooning. Reviews in cardiovascular medicine 2007;8:228-233.
• Bruder-Nascimento T, Campos DHS, Leopoldo AS, Lima-Leopoldo AP, Okoshi K, Cordellini S et al. Chronic Stress Improves the Myocardial Function without Altering L-type Ca+2 Channel Activity in Rats. Arquivos Brasileiros De Cardiologia 2012;99:907-914.
• Vanltallie TB. Stress: A risk factor for serious illness. Metabolism-Clinical and Experimental 2002;51:40-45
• Tennant C. Work stress and coronary heart disease. Journal of cardiovascular risk 2000;7:273-276.
• Vlastelica M. Emotional stress as a trigger in sudden cardiac death. Psychiat Danub 2008;20:411-414.
• Kim YS, Lee MY, Choi CS, Sohn YW, Park BR, Choi MG et al. The effect of chronic variable stress on bowel habit and adrenal function in rats. Journal of gastroenterology and hepatology 2008;23:1840-1846.
• Ulrich-Lai YM, Figueiredo HF, Ostrander MM, Choi DC, Engeland WC, Herman JP. Chronic stress induces adrenal hyperplasia and hypertrophy in a subregion-specific manner. American journal of physiology. Endocrinology and metabolism 2006;291:E965-973.
• Diorio D, Viau V, Meaney MJ. The Role of the Medial Prefrontal Cortex (Cingulate Gyrus) in the Regulation of Hypothalamic-Pituitary-Adrenal Responses to Stress. J Neurosci 1993;13:3839-3847.
• Lo Sauro C, Ravaldi C, Cabras PL, Faravelli C, Ricca V. Stress, hypothalamic-pituitary-adrenal axis and eating disorders. Neuropsychobiology 2008;57:95-115.
• Desborough JP. The stress response to trauma and surgery. Brit J Anaesth 2000;85:109-117.
• Tsigos C, Chrousos GP. Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. J Psychosom Res 2002;53:865-871.
• Milik E, Cudnoch-Jedrzejewska A, Szczepanska-Sadowska E. Effect of Chronic Mild Stress on AT1 Receptor Messenger RNA Expression in the Brain and Kidney of Rats. Psychosom Med 2016;78:208-220.
• Benchimol de Souza D, Silva D, Marinho Costa Silva C, Barcellos Sampaio FJ, Silva Costa W, Martins Cortez C. Effects of immobilization stress on kidneys of Wistar male rats: a morphometrical and stereological analysis. Kidney Blood Press Res 2011;34:424-429.
• Dalla C, Antoniou K, Drossopoulou G, Xagoraris M, Kokras N, Sfikakis A et al. Chronic mild stress impact: are females more vulnerable? Neuroscience 2005;135:703-714.
• Willner P. Chronic mild stress (CMS) revisited: consistency and behavioural-neurobiological concordance in the effects of CMS. Neuropsychobiology 2005;52:90-110.
• Willner P. Animal models of depression: an overview. Pharmacology & therapeutics 1990;45:425-455.
• Willner P. Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Psychopharmacology 1997;134:319-329.
• Demirci T, Sahin E. Heart And Stress: A Morphometric and Light Microscopic Study In A Rat Model. Averroes European Medical Journal 2017;4:1-9.
• Demirci T. Kronik strese ve yağlı diyete maruz bırakılan sıçanlarda testis ve spermlerin immunhistokimyasal ve morfometrik yöntemler eşliğinde ışık mikroskobik değerlendirilmesi. Tıpta Uzmanlık Tezi, Atatürk Üniversitesi 2011.
• Altunkaynak BZ, Ozbek E. Overweight and structural alterations of the liver in female rats fed a high-fat diet: a stereological and histological study. Turk J Gastroenterol 2009;20:93-103.
• Demirci T, Ozbek E. Volumetric and light microscopic analyses of adrenal glands in stress-administrated female rats. Surg Radiol Anat 2009; 31(suppl): 125.
• Bhatt S, Radhakrishnan M, Jindal A, Devadoss T, Dhar AK. Neuropharmacological evaluation of a novel 5-HT3 receptor antagonist (6g) on chronic unpredictable mild stress-induced changes in behavioural and brain oxidative stress parameters in mice. Indian J Pharmacol 2014;46:191-196.
• Hu Y, Gursoy E, Cardounel A, et al. Biological effects of single and repeated swimming stress in male rats: beneficial effects of glucocorticoids. Endocrine 2000;13:123-129.
• Aschbacher K, O'Donovan A, Wolkowitz OM, Dhabhar FS, Su Y, Epel E. Good stress, bad stress and oxidative stress: insights from anticipatory cortisol reactivity. Psychoneuroendocrinology 2013;38:1698-1708.
• Gutierrez J, Ballinger SW, Darley-Usmar VM, Landar A. Free radicals, mitochondria, and oxidized lipids: the emerging role in signal transduction in vascular cells. Circ Res 2006;99:924-932.
• Aruoma OI. Free radicals, oxidative stress, and antioxidants in human health and disease. JAOCS 1998;75:199-211.
• Sies H. Oxidative stress: oxidants and antioxidants. Exp Physiol 1997;82:291-295.
• Locatelli F, Canaud B, Eckardt KU, Stenvinkel P, Wanner C, Zoccali C. Oxidative stress in end-stage renal disease: an emerging threat to patient outcome. Nephrol Dial Transplant 2003;18:1272-1280.
• Handelman GJ. Evaluation of oxidant stress in dialysis patients. Blood Purif 2000;18:343-349.
• Sena LA, Chandel NS. Physiological roles of mitochondrial reactive oxygen species. Mol Cell 2012;48:158-167.
• Kim HJ, Vaziri ND, Norris K, An WS, Quiroz Y, Rodriguez-Iturbe B. High-calorie diet with moderate protein restriction prevents cachexia and ameliorates oxidative stress, inflammation and proteinuria in experimental chronic kidney disease. Clin Exp Nephrol 2010;14:536-547.
• Rajavel V, Abdul Sattar MZ, Abdulla MA, Kassim NM, Abdullah NA. Chronic Administration of Oil Palm (Elaeis guineensis) Leaves Extract Attenuates Hyperglycaemic-Induced Oxidative Stress and Improves Renal Histopathology and Function in Experimental Diabetes. Evid Based Complement Alternat Med 2012;2012:195367.
• Lee EA, Seo JY, Jiang Z, Yu MR, Kwon MK, Ha H et al. Reactive oxygen species mediate high glucose-induced plasminogen activator inhibitor-1 up-regulation in mesangial cells and in diabetic kidney. Kidney Int 2005;67:1762-1771.
• Baliga R, Ueda N, Walker PD, Shah SV. Oxidant mechanisms in toxic acute renal failure. Drug Metab Rev 1999;31:971-997.
• Klahr. Urinary tract obstruction. Semin Nephrol 2001;21:133-145.
• Sakatsume M, Kadomura M, Sakata I, Imai N, Kondo D, Osawa Y et al. Novel glomerular lipoprotein deposits associated with apolipoprotein E2 homozygosity. Kidney Int 2001;59:1911-1918.
• Kitamura M, Ishikawa Y. Oxidant-induced apoptosis of glomerular cells: intracellular signaling and its intervention by bioflavinoid. Kidney Int 1999;56:1223-1229.
• Handelman GJ, Walter MF, Adhikarla R, Gross J, Dallal GE, Levin NW et al. Elevated plasma F2-isoprostanes in patients on long-term hemodialysis. Kidney Int 2001;59:1960-1966.
• Baud L, Ardaillou R. Involvement of reactive oxygen species in kidney damage. Br Med Bull 1993;49:621-629.
• Baker GL, Corry RJ, Autor AP. Oxygen free radical induced damage in kidneys subjected to warm ischemia and reperfusion. Protective effect of superoxide dismutase. Ann Surg 1985;202:628-641.
• Rodrigo R, Bosco C. Oxidative stress and protective effects of polyphenols: comparative studies in human and rodent kidney. A review. Comp Biochem Physiol C Toxicol Pharmacol 2006;142:317-327.
• Antunes LM, Darin JD, Bianchi Nde L. Effects of the antioxidants curcumin or selenium on cisplatin-induced nephrotoxicity and lipid peroxidation in rats. Pharmacol Res 2001;43:145-150.
• Hannemann J, Baumann K. Cisplatin-induced lipid peroxidation and decrease of gluconeogenesis in rat kidney cortex: different effects of antioxidants and radical scavengers. Toxicology 1988;51:119-132.
• Sadzuka Y, Shoji T, Takino Y. Mechanism of the increase in lipid peroxide induced by cisplatin in the kidneys of rats. Toxicol Lett 1992;62:293-300.
• Sugihara K, Nakano S, Koda M, Tanaka K, Fukuishi N, Gemba M. Stimulatory effect of cisplatin on production of lipid peroxidation in renal tissues. Jpn J Pharmacol 1987;43:247-252.
• Tarladacalisir YT, Kanter M, Uygun M. Protective effects of vitamin C on cisplatin-induced renal damage: a light and electron microscopic study. Ren Fail 2008;30:1-8.
• Nirmal J, Babu CS, Harisudhan T, Ramanathan M. Evaluation of behavioural and antioxidant activity of Cytisus scoparius Link in rats exposed to chronic unpredictable mild stress. BMC Complement Altern Med 2008;8:15.
• Evans JL, Goldfine ID, Maddux BA, Grodsky GM. Are oxidative stress-activated signaling pathways mediators of insulin resistance and beta-cell dysfunction? Diabetes 2003;52:1-8.
• CeballosPicot I, WitkoSarsat V, MeradBoudia M, Nguyen AT, Thevenin M, Jaudon MC et al. Glutathione antioxidant system as a marker of oxidative stress in chronic renal failure. Free Radical Biology and Medicine 1996;21:845-853.
• Baud L, Ardaillou R. Reactive Oxygen Species - Production and Role in the Kidney. American Journal of Physiology 1986;251:F765-F776.
• Vaziri ND, Bai Y, Ni Z, Quiroz Y, Pandian R, Rodriguez-Iturbe B. Intra-renal angiotensin II/AT1 receptor, oxidative stress, inflammation, and progressive injury in renal mass reduction. J Pharmacol Exp Ther 2007;323:85-93.
• Yoshioka T, Bills T, Moorejarrett T, Greene HL, Burr IM, Ichikawa I. Role of Intrinsic Antioxidant Enzymes in Renal Oxidant Injury. Kidney International 1990;38:282-288.