Effects of the melatonin on the kidney of high fat diet fed obese rats: A stereological and histological approach

Kıymet Kübra YURT, Elif KAYHAN, B. Zuhal ALTUNKAYNAK, Gamze TÜMENTEMUR, Süleyman KAPLAN
2.789 769

Abstract


Obesity is associated with multiple conditions that are known to compromise renal function, including hypertension, diabetes, hyperuricemia, and the metabolic syndrome that can independently have a detrimental effect on renal function. The aim of this study was to examine effects of fatty diet induced obesity and melatonin on kidney in female rats by histological and quantative methods. For this aim, 24 rats were randomly divided into 4 groups including Non-obese control (NC group), Obese control (OC group), Nonobese Melatonin (NOM group) and Obese-Melatonin (OM group) groups. In the obese groups, rats, were fed with high fat diet (40% of calories from fat) for 15 weeks. The rats of the non-obese groups were fed with standard, commercial rat diet during the same period. At the end of the 15th week, rats in the melatonin groups started to received daily injections (i.p.) 10 mg/kg melatonin for 6 weeks. At the end of the experiment, a serial sections of kidneys were stained with Hematoxylen-eosin. Glomerular number (Ng) is considered a major determinant of renal function and outcome. Unbiased stereo logical methods have been used to estimate of Ng. Also histopathological analysis was made on the same sections. Stereological examination of the kidneys showed differences in terms of total kidney volume, volume of cortex, medulla and numerical density of glomeruli among the groups. Light microscopic investigation showed a dilatation in blood vessels and Bowman’s space, mononuclear cell infiltration, degeneration in nephrons, including glomerulosclerosis and tubular defects, and an increase in the connective tissue in the kidneys in the OC group. But, both stereological deficits and histological damages detected in OC group recovered in OM group after melatonin treatment. We suggested that a fatty diet is responsible for the rats’ obesity and may lead to renal deformities as a result of histopathological changes such as vessel dilatation, tubular defects, inflammation and connective tissue enlargement of the kidney. Also melatonin treatment after obesity may contribute structural and functional healing.

Keywords


Obesity; kidney; melatonin; glomerulus; stereology; physical disector

Full Text:

153-158


DOI: http://dx.doi.org/10.5835/jecm.omu.30.02.013

References


Altunkaynak, B.Z., 2005. Effects of high fat diet induced obesity on female rat livers (a histochemical study). Eur. J. Gen. Med. 2, 100-109.

Altunkaynak, B.Z., Özbek, E., 2006. Obezite: Nedenleri ve tedavi seçenekleri. Van Tıp Dergisi. 13, 138-142.

Altunkaynak M. E., Özbek, E., Altunkaynak, B. Z, Can, I., Unal, D., Unal, B., 2008. The effects of high-fat diet on the renal structure and morphometric parametric of kidneys in rats. J Anat. 6, 845-852.

Aguila, M.B., Mandarim-De-Lacerda, C.A., 2003. Effects of chronic high fat diets on renal function and cortical structure in rats. Exp. Toxicol Pathol. 55, 187-195.

Arangino, S., Cagnacci, A., Angiolucci, M., Vacca, A.M., Longu, G., Volpe, A., Melis, G.B., 1999. Effects of melatonin on vascular reactivity, catecholamine levels, and blood pressure in healthy men. Am. J. Cardiol. 83, 1417-1419.

Armitage, J.A., Lakasing, L., Taylor, P.D., Balachandran, A.A., Jensen, R.I., Dekou, V., Ashton, N., Nyengaard, J.R., Poston, L., 2005. Developmental programming of aortic and renal structure in offspring of rats fed fat-rich diets in pregnancy. J. Physiol. 565, 171-184.

Bosma, R.J., van der Heide, J.J., Oosterop, E.J., de Jong, P.E., Navis, G., 2004. Body mass index is associated with altered renal hemodynamics in non-obese healthy subjects. Kidney Int. 65, 259-265.

Bosma, R.J., Krikken, J.A., Homan, J.J., van der Heide, de Jong, P.E., Navis, G., 2006. Obesity and renal hemodynamics. Contrib. Nephrol. 151, pp. 184-202.

Burgess, H.J., Sletten, T., Savic, N., Gilbert, S.S., Dawson, D., 2001. Effects of bright light and melatonin on sleep propensity temperature and cardiac activity at night. J. Appl. Physiol. 91, 1214-1222.

Cavallo, A., Daniels, S.R., Dolan, L.M., Bean, J.A., Khoury, J.C., 2004a. Blood pressure-lowering effect of melatonin in type 1 diabetes. J. Pineal Res. 36, 262-266.

Cavallo, A., Daniels, S.R., Dolan, L.M., Khoury, J.C., Bean, J.A., 2004b. Blood pressure response to melatonin in type 1 diabetes. Pediatr. Diabetes. 5, 26-31.

Chen, J., Muntner, P., Hamm, L.L., Jones, D.W., Batuman, V., Fonseca, V., Whelton, P.K., He, J., 2004. The metabolic syndrome and chronic kidney disease in U.S. adults. Ann. Intern. Med. 140, 167-174.

Ding, C.N., Cao, Y.X., Zhou, L., Zhu, D.N., Shen, Z.Y., Fei, M.Y., Yu, P., 2001. Effects of microinjection of melatonin and its receptor antagonists into anterior hypothalamic area on blood pressure and heart rate in rats. ActaPharmacol. Sin. 22, 997–1002.

Drew, J.E., Williams, L.M., Hannalı, L.T., Barrett, P., Abramovich, D.R., 1998. Melatonin receptors in the human fetal kidney: 2-[1 125] iodomelatonin binding sites cornelated with expression of Mel 1a and Mel 1b receptor genes. J. Endocrinol. 156, 261-267.

Gilat, T., Leikin-Frenkel, A., Goldiner, I., Juhel, C., Lafont, H., Gobbi, D., Konikoff, F.M., 2003. Prevention of diet-induced fatty liver in experimental animals by the oral administration of a fatty acid bile acid conjugate (FABAC). Hepatology; 38, 436-442.

Girouard, H., Chulak, C., Kejossec, M., Lamontahne, D., Champlain, Y., 2002. Vasorelexant effects of the chronic treatment with melatonin on mesenteric artery and aorta of spontaneously hypertansive rats. J. Hypertens. 19, 1369-1377.

Griffin, K.A., Kramer, H., Bidani, A.K., 2008. Adverse renal consequences of obesity. Am. J. Physiol Renal Physiol. 294, 685-696.

Gundersen, H.J.G., Jensen, E.B., 1987. The efficiency of systematic sampling in stereology and its prediction. J. Microsc. 147, 229-263.

Hall, J.E., Kuo, J.J., da Silva, A.A., de Paula, R.B., Liu, J., Tallam, L., 2003a. Obesity-associated hypertension and kidney disease. Curr. Opin Nephrol. Hypertens. 195-200.

Hall, J.E., Jones, D.W., Kuo, J.J., da Silva, A., Tallam, L.S., Liu, J., 2003b. Impact of the obesity epidemic on hypertension and renal disease. CurrHypertens Rep. 386-392.

Hall, J.E., 1994. Renal and cardiovascular mechanisms of hypertension in obesity. Hypertension. 23, 381-394.

Handa, K., Kreiger, N., 2002. Diet patterns and the risk of renal cell carcinoma. Public Health Nutr. 5, 757-767.

Isomaa, B., Almgren, P., Tuomi, T., Forsén, B., Lahti, K., Nissén, M., Taskinen, M.R., Groop, L., 2001. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care. 24, 683-689.

Jiang, T., Wang, Z., Proctor, G., Proctor, G., Moskowitz, S., Liebman, S.E., Rogers, T., Lucia, M.S., Li, J., Levi, M., 2005. Diet-induced obesity in C57BL/6J mice causes increased renal lipid accumulation and glomerulosclerosis via a sterol regulatory element-binding protein-1cdependent pathway. J. Biol. Chem. 280, 32317-32325.

Kaplan, S., Gokyar, A., Unal, B., Tunç, A.T., Bahadir, A., Aslan, H., 2005. A simple technique for localizing consecutive fields for disector pairs in light microscopy: Application to neuron counting in rabbit spinal cord following spinal cord injury. J. Neurosci Methods. 145, 277-284. Karppanen, H., Vapaatalo, H., Lahovaara, S., Paasonen, M.K., 1970. Studies with pinealectomized rats. Pharmacology. 3, 76-84.

Kasiske B.L., Napier J., 1985. Glomerular sclerosis in patients with massive obesity. Am J Nephrol. 5, 45-50.

Kramer, H.J., Saranathan, A., Luke, A., et al. 2006. Increasing body mass index and obesity in the incident ESRD population. J Am SocNephrol. 17, 1453-1459.

Kramer, H., Luke, A., Obesity and kidney disease: A big dilemma. 2007. Curr. Opin. Nephrol. Hypertens. 16, 237-241.

Laflamme, A.K., WU, L., Faucart, S., Champlain, Y., 1998. Impaired basal sympathetic tone and alfa1 adrenergic responsiveness in association with the hypotensive effect of melatonin in spontaneously hypertensive rats. Am. J. Hypertens. 11, 219-222.

Lakka, H.M., Laaksonen, D.E., Lakka, T.A., Niskanen, L.K., Kumpusalo, E., Tuomilehto, J., Salonen, JT., 2002. The metabolic syndrome and total and cardiovascular disease mortality in middLle-aged men. J. Am. Med. Assoc. 288, 2709-2716.

Nowak, Y.Z., Zawilsha, Y.B., 1998. Melatonin and its physiological and therapeutic properties. Pharm. World. Sci. 20, 18-27.

Nicol, C.J., Adachi, M., Akiyama, T.E., Gonzalez, F.J., 2005. PPARgamma in endothelial cells influences high fat diet-induced hypertension. Am. J. Hypertens. 18: 549-56.

Praga, M., Hernandez, E., Andres, A., Leon, M., Ruilope, M.L., Rodicio LJ., 1995. Effects of body-weight loss and captopril treatment on proteinuria associated with obesity. Nephron. 70, 35-41.

Praga, M., Hernández, E., Morales, E., et al., 2001. Clinical features and long-term outcome of obesity-associated focal segmental glomerulosclerosis. Nephrol. Dial. Transplant. 16, 1790-1798.

Prunet-Marcassus, B., Desbazeille, M., Bros, A., Louche, K., Delagrange, P., Renard, P., et al., 2003. Melatonin reduces body weight gain in Sprague Dawley rats with diet-induced obesity. Endocrinology. 144, 5347-5352.

Quiroz, Y., Ferrebuz, A., Romero, F., Vaziri, N.D., Rodriguez-Iturbe, B., 2008. Melatonin ameliorates oxidative stress, inflammation, proteinuria, and progression of renal damage in rats with renal mass reduction. Am. J. Physiol Renal Physiol. 294, 336-344.

Rasmussen, D.D., Boldt, B.M., Wilkinson, C.W., Yellon, S.M., Matsumoto, A.M., 1999. Daily melatonin administration at middle age suppresses male rat visceral fat, plasma leptin, and plasma insulin to youthful levels. Endocrinology. 140, 1009-1012.

Sahin, B., Emirzeoglu, M., Uzun, A., Incesu, L., Bek, Y., Bilgic, S., Kaplan, S., 2003. Unbiased estimation of the liver volume by the Cavalieri principle using magnetic resonance images. Eur. J. Radiol. 47: 164-170.

Scheer, F.A., Van Montfrans, G.A,. et al. 2004. Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension. Hypertension. 43, 192-197.

Shoham, D.A., Vupputuri, S., Kshirsagar, A.V., 2005. Chronic kidney disease and life course socioeconomic status: A review. Adv. Chronic Kidney Dis. 12, 56-63.

Song, Y., Poon, A.M.S., Lee, P.P.N., Pamg, S.F., 1993. Putative melatonin receptors in the male guinea pig kidney. J. Pineal Res.15, 153-160. Sterio, D.C., 1984. The unbiased estimation of number and sizes of arbitrary particles using the disector. J. Microsc. 134, 127-136.

Unal, B., Özbek, M.E., Aydin, M.D., et al., 2004. Effect of haloperidol on the numerical density of neurons and nuclear height in the rat hippocampus: a stereological and histopathological study. Neurosci Res. Commun. 34, 1-9.

Usardi, P., Preti, P., et al., 1997. Effect of bed time melatonin ingestion on blood pressure of normotensive subjects. Blood. Press. Monit. 2, 99

Yilmaz, A., Suleyman, H., Umudum, Z., Sahin, Y.N., 2002. The effect of adrenalectomy on leptin levels and some metabolic parameters in rats with diet-induced obesity. Biol. Pharm. Bull. 25, 580-583.

Zanoboni, A., Zanoboni-Muciaccia, W., 1967. Experimental hypertension in pinealectomized rats. Life Sci. 6, 2327-2331.