Protective Effects of Leptin on Ischemia/Reperfusion Injury in Rat Bladder

10.4077/CJP.2010.AMK035

Mehmet Hamarat；Aydın Yenilmez；Nilufer Erkasap；Burhanettin Isikli；Erinc Aral；Tulay Koken；Cavit Can；Canan Baydemir Demirustu

ischemia/reperfusion injury ； oxidative stress ； leptin ； rat ； urinary bladder ； apoptosis

The Chinese Journal of Physiology

53卷3期（2010 / 06 / 01）

145 - 150

英文

The aim of the study was to evaluate protective effects of exogenous leptin on ischemia/reperfusion (I/R)-induced injuries to the urinary bladder tissue and to investigate the effect on tumor necrosis factor (TNF-α) levels and apoptotic cells during I/R injury. Bladder I/R injury was induced by abdominal aorta occlusion by ischemia for 45 min, followed by 60 min of reperfusion in rats. The rats were divided into three groups: control (n=8+8), I/R (n=8+8) and I/R+leptin group (n=8+8). The rats in the I/R+ leptin group were treated intraperitoneally with leptin (10μg/kg) 60 min prior to ischemia induction. At the end of the reperfusion period, urinary bladders of the first eight rats from each group were removed for TUNEL staining processing while the others were removed for biochemical analyses for MDA and TNF-α levels. In the I/R group, the ratios of TUNEL-positive nuclei were higher than the control and the I/R+ leptin groups. The MDA and TNF-ct levels of the bladder tissue in the I/R group were higher than the control and leptin-treated groups. TUNEL-staining and biochemical studies revealed that leptin has a protective effect on urinary bladder I/R injury.

1. Bratslavsky, G.,Kogan, B. A.,Matsumoto, S.,Aslan, A. R.,Levin, R. M.(2003).Reperfusion injury of the rat bladder is worse than ischemia.J. Urol.,170,2086-2090.
2. Bratslavsky, G.,Kogan, B.,Levin, R. M.(2001).Urethra is more sensitive to ischemia than bladder: evidence from an in vitro rat study.J. Urol.,165,2086-2090.
3. Bratslavsky, G.,Whitbeck, C.,Horan, P.,Levin, R. M.(1999).Effects of in vivo ischemia on contractile responses of rabbit bladder to field stimulation, carbachol, ATP and KCl.Pharmacology,59,221-226.
4. Brzozowski, T.,Konturek, P. C.,Pajdo, R.,Kwiecien, S.,Ptak, A.,Sliwowski, Z.,Drozdowicz, D.,Pawlik, M.,Konturek, S. J.,Hahn, E. G.(2001).Brain-gut axis in gastroprotection by leptin and cholecystokinin against ischemia-reperfusion induced gastric lesions.J. Physiol. Pharmacol.,52,583-602.
5. Colletti, L. M.,Remick, D. G.,Burtch, G. D.,Kunkel, S. L.,Strieter, R. M.,Campbell, D. A., Jr.(1990).Role of tumor necrosis factor-α in the pathophysiologic alterations after hepatic ischemia/reperfusion injury in rat.J. Clin. Invest.,85,1936-1943.
6. Donnahoo, K. K.,Meng, X.,Ayala, A.,Cain, M. P.,Harken, A. H.,Meldrum, D. R.(1999).Early kidney TNF-α expression mediates neutrophil infiltration and injury after renal ischemia-reperfusion.Am. J. Physiol.,277,R922-R929.
7. Erkasap, N.,Ikizler, M.,Shneyvays, V.,Zinman, T.,Mamedova, L. K.,Uyar, R.,Shainberg, A.(2006).Leptin protects the cardiac myocyte cultures from hypoxic damage.Life Sci.,78,1098-1102.
8. Erkasap, N.,Uzuner, K.,Serteser, M.,Köken, T.,Aydin, Y.(2003).Gastroprotective effect of leptin on gastric mucosal injury induced by ischemia-reperfusion is related to gastric histamine content in rats.Peptides,24,1181-1187.
9. Erkasap, S.,Erkasap, N.,Koken, T.,Kahraman, A.,Uzuner, K.,Yazihan, N.,Ates, E.(2004).Effect of leptin on renal ischemiareperfusion damage in rats.J. Physiol. Biochem.,60,79-84.
10. Hacioglu, A.,Algin, C.,Pasaoglu, O.,Pasaoglu, E.,Kanbak, G.(2005).Protective effect of leptin against ischemia-reperfusion injury in rat small intestine.BMC Gastroenterol.,5,37.
11. Janero, D. R.(1990).Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury.Free Radic. Biol. Med.,9,515-540.
12. Kahraman, A.,Erkasap, N.,Serteser, M.,Koken, T.(2003).Protective effect of quercetin on renal ischemia/reperfusion injury in rats.J. Nephrol.,16,219-224.
13. Levin, R. M.,Leggett, R.,Whitbeck, C.,Horan, P.(1998).Effect of calcium and calcium chelators on the response of the bladder to in vitro ischemia.Br. J. Urol.,82,882-887.
14. Levin, R. M.,Whitbeck, C.,Horan, P.,Bellamy, F.(2005).Low-dose tadenan® protects the rabbit bladder from bilateral ischemia/reperfusion induced contractile dysfunction.Phytomedicine,12,17-24.
15. Li Volti, G.,Sorrent, V.,Murabito, P.,Galvano, F.,Veroux, M.,Gullo, A.,Acquaviva, R.,Stacchiotti, A.,Bonomini, F.,Vanella, L.,Di Giacomo, C.(2007).Pharmacological induction of heme oxygenase-1 inhibits iNOS and oxidative stress in renal ischemiareperfusion injury.Transplant. Proc.,39,2986-2991.
16. Lin, A. T.,Chen, M. T.,Yang, C. H.,Chang, L. S.(1995).Blood flow of the urinary bladder: effects of outlet obstruction and correlation with bioenergetic metabolism.Neurourol. Urodyn.,14,285-292.
17. Meldrum, K. K.,Meldrum, D. R.,Hile, K. L.,Burnett, A. L.,Harken, A. H.(2001).A novel model of ischemia in renal tubuler cells which closely parallels in vivo injury.J. Surg. Res.,99,288-293.
18. Ogunwobi, O. O.,Beales, I. L.(2007).The anti-apoptotic and growth stimulatory actions of leptin in human colon cancer cells involves activation of JNK mitogen activated protein kinase, JAK2 and PI3 kinase/Akt.Int. J. Colorectal Dis.,22,401-409.
19. Ohkawa, H.,Ohishi, N.,Yagi, K.(1979).Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction.Anal. Biochem.,95,351-358.
20. Ozdemir, D.,Uysal, N.,Tugyan, K.,Gonenc, S.,Acikgoz, O.,Aksu, I.,Ozkan, H.(2007).The effect of melatonin on endotoxemia-induced intestinal apoptosis and oxidative stress in infant rats.Intensive Care Med.,33,511-516.
21. Rhoden, E. L.,Pereira-Lima, L.,Teloken, C.,Lucas, M. L.,Bello-Klein, A.,Rhoden, C. R.(2001).Beneficial effect of alpha-tocopherol in renal ischemia-reperfusion in rats.Jpn. J. Pharmacol.,87,164-166.
22. Serteser, M.,Koken, T.,Kahraman, A.,Yilmaz, K.,Akbulut, G.,Dilek, O. N.(2002).Changes in hepatic TNF-α levels, antioxidant status, and oxidation products after renal ischemia/reperfusion injury in mice.J. Surg. Res.,107,234-240.
23. Villarreal, D.,Reams, G.,Freeman, R. H.,Taraben, A.(1998).Renal effects of leptin in normotensive, hypertensive, and obese rats.Am. J. Physiol.,275,R2056-R2060.
24. Vinas, J. L.,Sola, A.,Genesca, M.,Alfaro, V.,Pi, F.,Hotter, G.(2006).NO and NOS isoforms in the development of apoptosis in renal ischemia/reperfusion.Free Radic. Biol. Med.,40,992-1003.
25. Yenilmez, A.,Kilic, F. S.,Sirmagul, B.,Isikli, B.,Aral, E.,Oner, S.(2007).Preventive effects of Ginkgo biloba extract on ischemiareperfusion injury in rat bladder.Urol. Int.,78,167-172.
26. Yildirim, A.,Onol, F.F.,Haklar, G.,Tarcan, T.(2008).The role of free radicals and nitric oxide in the ischemia-reperfusion injury mediated by acute bladder outlet obstruction.Int. Urol. Nephrol.,40,71-77.

1. (2013).Effects of 3,5,3'-Triiodothyronine (T3) and Follicle Stimulating Hormone on Apoptosis and Proliferation of Rat Ovarian Granulosa Cells.中國生理學雜誌,56(5),298-305.