Skip to main content

Advertisement

Log in

Ghrelin Acts as an Antioxidant Agent in the Rat Kidney

  • Published:
International Journal of Peptide Research and Therapeutics Aims and scope Submit manuscript

Abstract

Ghrelin has recently been shown to improve renal function in rat with acute renal failure. In this setting, the protective effects have been suggested to be due to its antioxidant properties. Thus, the aim of this study was to measure the antioxidant abilities of this hormone via enzymatic and lipid peroxidation analyses. Wistar rats were divided into two control and two treatment groups, the treated animals receiving 3 nmol of ghrelin as subcutaneous administrations on each of 10 consecutive days and physiological saline injected to controls. Catalase (CAT) activity was significantly higher in the treated animals when compared to controls, while in contrast, lipid peroxidation measured by thiobarbituric acid reactive substances (TBARS), was significantly reduced in the ghrelin treated animals. Furthermore, superoxide dismutase (SOD) activity and glutathione (GSH) content were both much higher in treated female rats than in controls and although there was a slight increase in glutathione peroxidase (GPx) activity in kidneys of ghrelin treated rats, the difference was insignificant. These findings suggest that ghrelin has beneficial antioxidant properties in the rat kidney by increasing antioxidant enzyme activities. These effects were more noticeable in treated female rats, possibly due to higher levels of estrogen.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Ashby DR, Ford HE, Wynne KJ, Wren AM, Murphy KG, Busbridge M, Brown EA, Taube DH, Ghatei MA, Tam FWK (2009) Sustained appetite improvement in malnourished dialysis patients by daily ghrelin treatment. Kidney Int 76(2):199–206

    Article  PubMed  CAS  Google Scholar 

  • Atmaca M, Fry JR (1996) Adenosine-mediated inhibition of glutathione synthesis in rat isolated hepatocytes. Biochem Pharmacol 52(9):1423–1428

    Article  PubMed  CAS  Google Scholar 

  • Boger RH, Skamira C, Bode-Bger SM, Brabant G, Von Zur Muhlen A, Frolich JC (1996) Nitric oxide may mediate the hemodynamic effects of recombinant growth hormone in patients with acquired growth hormone deficiency: a double-blind, placebo-controlled study. J Clin Invest 98(12):2706–2713

    Article  PubMed  CAS  Google Scholar 

  • Claiborne A (1986) Catalase activity. In: Greenwald RA (ed) CRC handbook of methods for oxygen radical research. CRC Press, Boca Raton, pp 283–284

    Google Scholar 

  • Englander EW, Gomez GA, Greeley GH (2004) Alterations in stomach ghrelin production and in ghrelin-induced growth hormone secretion in the aged rat. Mech Ageing Dev 125(12):871–875

    Article  PubMed  CAS  Google Scholar 

  • Ergüder IB, etin R, Devrim E, KilI oglu B, AvcI AI, Durak I (2005) Effects of cyclosporine on oxidant/antioxidant status in rat ovary tissues: protective role of black grape extract. Int Immunopharmacol 5(7–8):1311–1315

    Article  PubMed  Google Scholar 

  • Fernandez-Fernandez R, Navarro VM, Barreiro ML, Vigo EM, Tovar S, Sirotkin AV, Casanueva FF, Aguilar E, Dieguez C, Pinilla L (2005) Effects of chronic hyperghrelinemia on puberty onset and pregnancy outcome in the rat. Endocrinology 146(7):3018–3025

    Article  PubMed  CAS  Google Scholar 

  • Gambineri A, Pagotto U, Tschöp M, Vicennati V, Manicardi E, Carcello A, Cacciari M, De Iasio R, Pasquali R (2003) Anti-androgen treatment increases circulating ghrelin levels in obese women with polycystic ovary syndrome. J Endocrinol Invest 26(7):629–634

    PubMed  CAS  Google Scholar 

  • Garcia YJ, Rodriguez-Malaver AJ, Penaloza N (2005) Lipid peroxidation measurement by thiobarbituric acid assay in rat cerebellar slices. J Neurosci Methods 144(1):127–135

    Article  PubMed  CAS  Google Scholar 

  • Ghelardoni S, Carnicelli V, Frascarelli S, Ronca-Testoni S, Zucchi R (2006) Ghrelin tissue distribution: comparison between gene and protein expression. J Endocrinol Invest 29(2):115–121

    PubMed  CAS  Google Scholar 

  • Gnanapavan S, Kola B, Bustin SA, Morris DG, McGee P, Fairclough P, Bhattacharya S, Carpenter R, Grossman AB, Korbonits M (2002) The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab 87(6):2988–2991

    Article  PubMed  CAS  Google Scholar 

  • Ikizler TA (2007) Effects of glucose homeostasis on protein metabolism in patients with advanced chronic kidney disease. J Ren Nutr 17(1):13–16

    Article  PubMed  Google Scholar 

  • Iseri S, Sener G, Saglam B, Ercan F, Gedik N, Yegen B (2008) Ghrelin alleviates biliary obstruction-induced chronic hepatic injury in rats. Regul Pept 146(1–3):73–79

    Article  PubMed  CAS  Google Scholar 

  • Kawczynska-Drozdz A, Olszanecki R, Jawien J, Brzozowski T, Pawlik WW, Korbut R, Guzik TJ (2006) Ghrelin inhibits vascular superoxide production in spontaneously hypertensive rats. Am J Hypertens 19(7):764–767

    Article  PubMed  CAS  Google Scholar 

  • Kheradmand A, Alirezaei M, Asadian P, Rafiei Alavi E, Joorabi S (2009) Antioxidant enzyme activity and MDA level in the rat testis following chronic administration of ghrelin. Andrologia 41(6):335–340

    Article  PubMed  CAS  Google Scholar 

  • Kheradmand A, Alirezaei M, Birjandi M (2010) Ghrelin promotes antioxidant enzyme activity and reduces lipid peroxidation in the rat ovary. Regul Pept 162(1–3):84–89

    Article  PubMed  CAS  Google Scholar 

  • Kheradmand A, Dezfoulian O, Tarrahi MJ (2011) Ghrelin attenuates heat-induced degenerative effects in the rat testis. Regul Pept 167:97–104

    Article  PubMed  CAS  Google Scholar 

  • Kojima M, Kangawa K (2005) Ghrelin: structure and function. Physiol Rev 85(2):495–522

    Article  PubMed  CAS  Google Scholar 

  • Laviano A, Inui A, Marks DL, Meguid MM, Pichard C, Rossi Fanelli F, Seelaender M (2008) Neural control of the anorexia-cachexia syndrome. Am J Physiol Endocrinol Metab 295(5):E1000–E1008

    Article  PubMed  CAS  Google Scholar 

  • Laviano A, Krznaric Z, Sanchez-Lara K, Preziosa I, Cascino A, Fanelli FR (2010) Chronic renal failure, cachexia, and ghrelin. Int J Pept 2010:1–5

    Article  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275

    PubMed  CAS  Google Scholar 

  • Miller SB, Martin DR, Kissane J, Hammerman MR (1992) Insulin-like growth factor I accelerates recovery from ischemic acute tubular necrosis in the rat. Proc Natl Acad Sci USA 89(24):11876–11880

    Article  PubMed  CAS  Google Scholar 

  • Mori K, Yoshimoto A, Takaya K, Hosoda K, Ariyasu H, Yahata K, Mukoyama M, Sugawara A, Hosoda H, Kojima M (2000) Kidney produces a novel acylated peptide, ghrelin. FEBS Lett 486(3):213–216

    Article  PubMed  CAS  Google Scholar 

  • Nagaya N, Uematsu M, Kojima M, Ikeda Y, Yoshihara F, Shimizu W, Hosoda H, Hirota Y, Ishida H, Mori H (2001) Chronic administration of ghrelin improves left ventricular dysfunction and attenuates development of cardiac cachexia in rats with heart failure. Circulation 104(12):1430–1435

    Article  PubMed  CAS  Google Scholar 

  • Obay BD, Tasdemir E, Tümer CI, Bilgin HIM, Atmaca M (2008) Dose dependent effects of ghrelin on pentylenetetrazole-induced oxidative stress in a rat seizure model. Peptides 29(3):448–455

    Article  PubMed  CAS  Google Scholar 

  • Pagel I, Langenickel T, Hohnel K, Philipp S, Nussler AK, Blum WF, Aubert ML, Dietz R, Willenbrock R (2002) Cardiac and renal effects of growth hormone in volume overload-induced heart failure: role of NO. Hypertension 39(1):57–62

    Article  PubMed  CAS  Google Scholar 

  • Pajovi SB, Saicic ZS (2008) Modulation of antioxidant enzyme activities by sexual steroid hormones. Physiol Res 57:801–811

    Google Scholar 

  • Peltola V, Huhtaniemi I, Ahotupa M (1992) Antioxidant enzyme activity in the maturing rat testis. J Androl 13(5):450–455

    PubMed  CAS  Google Scholar 

  • Rak A, Gregoraszczuk EL (2008a) Local feedback loop of ghrelin-GH in the pig ovary: action on estradiol secretion, aromatase activity and cell apoptosis. Growth Horm IGF Res 18(3):221–227

    Article  PubMed  CAS  Google Scholar 

  • Rak A, Gregoraszczuk EL (2008b) Modulatory effect of ghrelin in prepubertal porcine ovarian follicles. J Physiol Pharmacol 59(Suppl 4):781–793

    PubMed  CAS  Google Scholar 

  • Ross D (1988) Glutathione, free radicals and chemotherapeutic agents. Mechanisms of free-radical induced toxicity and glutathione-dependent protection. Pharmacol Ther 37(2):231–249

    Article  PubMed  CAS  Google Scholar 

  • Sedlak J, Lindsay RH (1968) Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem 25(1):192–205

    Article  PubMed  CAS  Google Scholar 

  • Sehirli O, Sener E, Sener G, Cetinel S, Erzik C, Yegen BC (2008) Ghrelin improves burn-induced multiple organ injury by depressing neutrophil infiltration and the release of pro-inflammatory cytokines. Peptides 29(7):1231–1240

    Article  PubMed  CAS  Google Scholar 

  • Stark GJ (2005) Functional consequences of oxidative membrane damage. J Membr Biol 205(1):1–16

    Article  PubMed  CAS  Google Scholar 

  • Subbarao KV, Richardson JS, Ang LC (1990) Autopsy samples of Alzheimer’s cortex show increased peroxidation in vitro. J Neurochem 55(1):342–345

    Article  PubMed  CAS  Google Scholar 

  • Takeda R, Nishimatsu H, Suzuki E, Satonaka H, Nagata D, Oba S, Sata M, Takahashi M, Yamamoto Y, Terauchi Y (2006) Ghrelin improves renal function in mice with ischemic acute renal failure. J Am Soc Nephrol 17(1):113–121

    Article  PubMed  CAS  Google Scholar 

  • Tesauro M, Schinzari F, Rovella V, Di Daniele N, Lauro D, Mores N, Veneziani A, Cardillo C (2009) Ghrelin restores the endothelin 1/nitric oxide balance in patients with obesity-related metabolic syndrome. Hypertension 54(5):995–1000

    Article  PubMed  CAS  Google Scholar 

  • Turner TT, Lysiak JJ (2008) Oxidative stress: a common factor in testicular dysfunction. J Androl 29(5):488–498

    Article  PubMed  CAS  Google Scholar 

  • Victor VM, Esplugues JV, Hernandez-Mijares A, Rocha M (2009) Oxidative stress and mitochondrial dysfunction in sepsis: a potential therapy with mitochondria-targeted antioxidants. Infect Disord Drug Targets 9(4):376–389

    PubMed  CAS  Google Scholar 

  • Wren AM, Small CJ, Abbott CR, Dhillo WS, Seal LJ, Cohen MA, Batterham RL, Taheri S, Stanley SA, Ghatei MA (2001) Ghrelin causes hyperphagia and obesity in rats. Diabetes 50(11):2540–2547

    Article  PubMed  CAS  Google Scholar 

  • Wynne K, Giannitsopoulou K, Small CJ, Patterson M, Frost G, Ghatei MA, Brown EA, Bloom SR, Choi P (2005) Subcutaneous ghrelin enhances acute food intake in malnourished patients who receive maintenance peritoneal dialysis: a randomized, placebo-controlled trial. J Am Soc Nephrol 16(7):2111

    Article  PubMed  CAS  Google Scholar 

  • Yada T, Kaiya H, Mutoh K, Azuma T, Hyodo S, Kangawa K (2006) Ghrelin stimulates phagocytosis and superoxide production in fish leukocytes. J Endocrinol 189(1):57–65

    Article  PubMed  CAS  Google Scholar 

  • Yagi K (1997) Female hormones act as natural antioxidants: a survey of our research. Acta Biochim Pol 44:701–710

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This research was financially supported by Razi Herbal Medicines Research Center, Lorestan University of Medical Science, Khorram Abad, Iran. The authors wish to thank Dr. A. Tamaddon (The member of Stem Cell and Transgenic Technology Research Center Shiraz University of Medical Sciences Shiraz, Iran) for his scientific comments, also like to thank Ms. Kolahi for expert revision on the final manuscript of this study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Masoud Alirezaei.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Neamati, S., Alirezaei, M. & Kheradmand, A. Ghrelin Acts as an Antioxidant Agent in the Rat Kidney. Int J Pept Res Ther 17, 239–245 (2011). https://doi.org/10.1007/s10989-011-9263-y

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10989-011-9263-y

Keywords

Navigation