Protective effects of ghrelin on kidney tissue in rats with partial ureteral obstruction
Protective effects of ghrelin on kidney tissue in rats with partial ureteral obstruction
Background/aim: The aim was to investigate the protective and therapeutic effects of ghrelin, which has antioxidant and antiinflammatoryactivity, on preventing kidney damage that occurs by induced partial ureteral obstruction in rats.Materials and methods: Twenty-eight adult male rats were included in the study, and the rats were divided into 4 groups. After thelaparotomy operation on the sham group, the ureter was identified in the retroperitoneal area and was duly sutured (n = 7). Ghrelinwas administered for seven days intraperitoneally, and after the nephrectomy performed on the 15th day, the rats were sacrificed (n =7). A partial ureteral obstruction was performed after the laparotomy on the PUO group. The rats were sacrificed after the nephrectomyoperation performed on the 15th day (n = 7). A partial ureteral obstruction was formed after the laparotomy followed by seven days ofwaiting in the PUO + ghrelin group. Ghrelin was given in the dose of 10 ng/kg per day intraperitoneally for the next 7 days, and the ratswere sacrificed after the nephrectomy operation performed on the 15th day (n = 7). All groups were evaluated for histological damageand catalase, superoxide dismutase, total glutathione, malondialdehyde, and myeloperoxidase levels were measured in the same tissues.Results: When the 2nd group and the sham group were compared histologically, it was observed that the damage had increased by astatistically significant level in the partial ureteral obstruction group (P = 0.001). When the group which was ghrelin-treated after thepartial ureteral obstruction was compared to the group with just partial ureteral obstruction, the histopathological changes were foundto decrease significantly in that group (P = 0.001). While the statistical significance of the levels of CAT, GSH, and MPO enzymes wasdetected among biochemical changes in the 2nd group when compared to the sham group (P < 0.01), the 3rd group showed a statisticallysignificant difference in the levels of SOD and GSH enzymes compared to the 4th group (P < 0.05).Conclusion: Ghrelin administration to rats after the formation of an experimental partial unilateral ureteral obstruction reduces tissuedamage due to ghrelin’s antiinflammatory and antioxidant effects. Ghrelin administration may prevent tissue damage biochemically andhistopathologically in obstructive uropathy cases.
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- 1. Lameire N, Van Biesen W, Vanholder R. Acute renal failure.
Lancet 2005; 365: 417-430.
- 2. Yokoyama H, Tsuji Y. Diuretic Doppler ultrasonography in
chronic unilateral partial ureteric obstruction in dogs. BJU Int
2002; 90: 100-104.
- 3. Klahr S. New insights into the consequences and mechanisms
of renal impairment in obstructive nephropathy. Am J Kidney
Dis 199; 18: 689-699.
- 4. Klahr S, Purkerson ML. The pathophysiology of obstructive
nephropathy: the role of vasoactive compounds in the
hemodynamic and structural abnormalities of the obstructed
kidney. Am J Kidney Dis 1994; 23: 219-223.
- 5. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H et al.
Ghrelin is a growth-hormone-releasing acylated peptide from
stomach. Nature 1999; 402: 656-660.
- 6. Bowers CY. Unnatural growth hormone-releasing peptide begets
natural ghrelin. J Clin Endocrinol Metab 2001; 86: 1464-1469.
- 7. Date Y, Kojima M, Hosoda H, Sawaguchi A, Mondal MS et al.
Ghrelin, a novel growth hormone-releasing acylated peptide is,
synthesized in a distinct endocrine cell type in the gastrointestinal
tract of rats and humans. Endocrinology 2000; 141: 4255-4261.
- 8. Kojima M, Kangawa K. Ghrelin: structure and function. Physiol
Rev 2005; 85: 495-522.
- 9. Aydın S, Özkan Y, Caylak E, Aydın S. Ghrelin and its biochemical
functions: review. Türkiye Klinikleri J Med Sci 2006; 26: 272-283
(in Turkish with abstract in English).
- 10. Aydin S, Aydin S, Ozkan Y, Kumru S. Ghrelin is present in
human colostrum, transitional and mature milk. Peptides 2006;
27: 878-882.
- 11. Kierson JA, Dimatteo DM, Locke RG, Mackley AB, Spear ML.
Ghrelin and cholecystokinin in term and preterm human breast
milk. Acta Paediatr 2006; 95: 991-995.
- 12. Aydinli S, Ozercan IH, Dagli F, Aydın S, Kumru S et al. Ghrelin is
present in teeth. J. Biochem Mol Biol 2007; 40: 368-372.
- 13. Aydın S. Ghrelin hormonunun keşfi: araştırmaları ve klinik
uygulamaları. Türk Biyokimya Dergisi 2007; 32: 76-89 (in
Turkish).
- 14. Baatar D, Patel K, Taub DD. The effects of ghrelin on inflammation
and the immune system. Mol Cell Endocrinol 2011; 340: 44-58.
- 15. Takeda R, Nishimatsu H, Suzuki E, Satonaka H, Nagata D et al.
Ghrelin improves renal function in mice with ischemic acute
renal failure. J Am Soc Nephrol 2006; 17: 113-121.
- 16. Chung H, Kim E, Lee DH, Seo S, Ju S et al. Ghrelin inhibits
apoptosis in hypothalamic neuronal cells during oxygen-glucose
deprivation. Endocrinology 2007; 148: 148-159.
- 17. Baldanzi G, Filigheddu N, Cutrupi S, Catapano F, Bonissoni
S et al. Ghrelin and des-acyl ghrelin inhibit cell death in
cardiomyocytes and endothelial cells through ERK1/2 and PI
3-kinase/AKT. J Cell Biol 2002; 159: 1029-1037.
- 18. Ersahin M, Toklu HZ, Erzik C, Cetinel S, Akakin D et al. The
antiinflammatory and neuroprotective effects of ghrelin in
subarachnoid hemorrhage-induced oxidative brain damage in
rats. J Neurotrauma 2010; 27: 1143-1155.
- 19. Iseri SO, Sener G, Saglam B, Ercan F, Gedik N et al. Ghrelin
alleviates biliary obstruction-induced chronic hepatic injury in
rats. Regul Pept 2008; 146: 73-79.
- 20. Li WG, Gavrila D, Liu X, Wang L, Gunnlaugsson S et al. Ghrelin
inhibits proinflammatory responses and nuclear factor-κB
activation in human endothelial cells. Circulation 2004; 109:
2221-2226.
- 21. Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H et al. A
role for ghrelin in the central regulation of feeding. Nature 2001;
409: 194-198.
- 22. Sehirli O, Sener E, Sener G, Cetinel S, Erzik C et al. Ghrelin
improves burn-induced multiple organ injury by depressing
neutrophil infiltration and the release of pro-inflammatory
cytokines. Peptides 2008; 29: 1231-1240.
- 23. Shimizu Y, Nagaya N, Teranishi Y, Imazu M, Yamamoto H et
al. Ghrelin improves endothelial dysfunction through growth
hormone-independent mechanisms in rats. Biochem Biophys
Res Commun 2003; 310: 830-835.
- 24. Ulm AH, Miller F. An operation to produce experimental
reversible hydronephrosis in dogs. J Urol 1962; 88: 337-341.
- 25. Eddy A. Molecular insights into renal interstitial fibrosis. J Am
Soc Nephrol 1996; 7: 2495-2508.
- 26. Truong LD, Petrusevska G, Yang G, Gurpinar T, Shappell S
et al. Cell apoptosis and proliferation in experiment chronic
obstructive uropathy. Kidney Int 1996; 50: 200-207.
- 27. Miyajima A, Ito K, Asana T, Seta K, Ueda A et al. Does
cyclooxygenase-2 inhibitor prevent renal tissue damage in
unilateral ureteral obstruction? J Urol 2001; 166: 1124-1129.
- 28. Miyajima A, Asano T, Asano T, Yoshimura I, Seta K et al.
Tranilast ameliorates renal tubular damage in unilateral
ureteral obstruction. J Urol 2001; 165: 1714-1718.
- 29. He P, Li D, Zhang B. Losartan attenuates renal interstitial
fibrosis and tubular cell apoptosis in a rat model of obstructive
nephropathy. Mol Med Rep 2014; 10: 638-644.
- 30. Topcu SO, Erbagci A, Erturhan S, Yagci F, Ucak R. Verapamil
attenuates renal tubular apoptosis in response to partial
unilateral ureteral obstruction. Urol Int 2008; 80: 84-89.
- 31. Guven B, Gokce M, Saydam O, Can M, Bektas S et al. Effect
of ghrelin on inflammatory response in lung contusion.
Kaohsiung J Med Sci 2013; 29: 69-74.
- 32. Lopez NE, Gaston L, Lopez KR, Coimbra RC, Hageny A et
al. Early ghrelin treatment attenuates disruption of the blood
brain barrier and apoptosis after traumatic brain injury
through a UCP-2 mechanism. Brain Res 2012; 13: 140-148.
- 33. Golestan Jahromi M, Nabavizadeh F, Vahedian J, Nahrevanian
H, Dehpour AR et al. Protective effect of ghrelin on
acetaminophen-induced liver injury in rat. Peptides 2010; 31:
2114-2117.
- 34. Alantary AK, Rezk MY, Khaled EAS. Protective effect of
ghrelin on paracetamol induced acute hepatotoxicity in rats. J
Physiol Pathophysiol 2014; 5: 7-14.
- 35. Pamukcu O, Kumral ZN, Ercan F, Yegen BC, Ertem D. Antiinflammatory effect of obestatin and ghrelin in dextran sulfate
sodium-induced colitis in rats. J Pediatr Gastroenterol Nutr
2013; 57: 211-218.
- 36. Khowailed A, Younan SM, Ashour H, Kamel AE, Sharawy N.
Effects of ghrelin on sepsis-induced acute kidney injury: one
step forward. Clin Exp Nephrol 2015; 19: 419-426.
- 37. Sahin S, Alata O. The role of ghrelin against acute carbon
tetrachloride hepatotoxicity in rats. Nobel Med 2013; 9: 43-48.