Effects of Functional Pinealectomy on Immunity, Hematopoietic, Gastrointestinal and Urinary Systems in Experimentally Malnutritioned Rats

Year 2024, , 324 - 333, 28.06.2024

Yaşar Barış Turgut , Cem Sahin , Yiğit Uyanıkgil , Mustafa Yılmaz , Canberk Tomruk , Cevat Gençer , Özge Çevik

https://doi.org/10.33808/clinexphealthsci.1259883

Abstract

Objective: The aim of this study was to demonstrate morphological changes in immunity, hematopoietic, gastrointestinal and urinary systems in different melatonin (MEL) release situations in a rat model of protein energy malnutrition (PEM).
Methods: A total of 32 adult male Wistar rats were assigned into four equal groups: normal control; PEM light/dark; PEM light, called functional pinealectomy (Px); and PEM dark. PEM was produced with a 50% restricted diet, Px was produced by keeping rats in continuous light environment for 24 hours, and complete blood count and serum albumin level were analyzed at the end of the 6-week experimental period. Measurements of weights of body and some visceral organs were obtained, biochemical and morphological parameters were analyzed in addition to measurements of malondialdehyde (MDA), total glutatione (GSH), tumor necrosis factor (TNF)-α and interleukin-10 (IL-10) in tissue samples.
Results: A reduction in the weights of body and visceral organs of animals in the PEM groups was accompanied by hypoalbuminemia, anemia, leukopenia and lymphopenia, and higher MDA, GSH, TNF-α and IL-10 levels in visceral tissues. There was a significant decrease in parenchymal cells of the liver and spleen, duodenal villi, lymphoid structures and kidney glomeruli, but there was an increase in the spleen capsule thickness and renal Bowman’s space, sinusoidal congestion and fat accumulation in the liver. Importantly, these findings were milder in the PEM dark group, while they were prominent in the PEM light group.
Conclusions: This study suggests that MEL has a protective role in reducing the negative effects of PEM, making it a potential therapeutic agent for further investigation.

Keywords

functional pinealectomy, malnutrition, melatonin, protein energy malnutrition, rat

Thanks

The authors acknowledge Rifat Aydın, Erdinç Yılmaz, and Timur Köse for their assistance during animal handling, technical assistance during during histological study, and help during statistical evaluation of the data, respectively. They are also grateful to Walter A. Hall, M.D. for his english language revision.

References

• Akinola FF, Oguntibeju OO, Alabi OO. Effects of severe malnutrition on oxidative stress in Wistar rats. Sci Res Essays. 2010;5(10):1145-1149.
• Chandra RK. Nutrition and the immune system: An introduction. Am J Clin Nutr. 1997;66(2):460S-463S. DOI: 10.1093/ajcn/66.2.460S.
• Müller O, Krawinkel M. Malnutrition and health in developing countries. CMAJ. 2005;173(3):279-286.
• Ortiz R, Cortés L, Cortés E, Medina H. Malnutrition alters the rates of apoptosis in splenocytes and thymocyte subpopulations of rats. Clin Exp Immunol. 2009;155(1):96-106. DOI: 10.1111/j.1365-2249.2008.03796.x
• Borelli P, Blatt SL, Rogero MM, Fock RA. Haematological alterations in protein malnutrition. Rev Bras Hematol Hemoter. 2004;26(1):49-56. DOI: 10.1590/S1516-84842004000100010
• Savino W. The thymus gland is a target in malnutrition. Eur J Clin Nutr. 2002;56(Suppl 3):S46-49.
• Stapleton PP, Fujita J, Murphy EM, Naama HA, Daly JM. The influence of restricted calorie intake on peritoneal macrophage function. Nutrition. 2001;17(1):41-45. DOI: 10.1016/s0899-9007(00)00502-5
• Fock RA, Vinolo MA, de Moura Sá Rocha V, de Sá Rocha LC, Borelli P. Protein-energy malnutrition decreases the expression of TLR-4/MD-2 and CD14 receptors in peritoneal macrophages and reduces the synthesis of TNF-alpha in response to lipopolysaccharide (LPS) in mice. Cytokine 2007;40(2):105-114. DOI: 10.1016/j.cyto.2007.08.007
• Katona P, Katona-Apte J. The interaction between nutrition and infection. Clin Infect Dis. 2008;46(10):1582-1588.
• Luo J, Zhang Z, Sun H, Song J, Chen X, Huang J, Lin X, Zhou R. Effect of melatonin on T/B cell activation and immune regulation in pinealectomy mice. Life Sci. 2020 Feb 1;242 117191. DOI: 10.1016/j.lfs.2019.117191
• Reiter RJ, Pablos MI, Agapito TT, Guerrero JM. Melatonin in the context of the free radical theory of aging. Ann NY Acad Sci. 1996;786:362-378.
• Reiter RJ. Oxidative damage in the central nervous system: Protection by melatonin. Prog Neurobiol. 1998;56(3):359-384.
• Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Guide for the Care and Use of Laboratory Animals (2011).
• Leite SN, Jordão Júnior AA, Andrade TA, Masson Ddos S, Frade MA. Experimental models of malnutrition and its effect on skin trophism. An Bras Dermatol. 2011;86(4):681-688. DOI: 10.1590/s0365-05962011000400009
• John TM, Brown MC, Wideman L, Brown GM. Melatonin replacement nullifies the effect of light-induced functional pinealectomy on nociceptive rhythm in the rat. Physiol Behav. 1994;55(4):735-739. DOI: 10.1016/0031-9384(94)90053-1
• NRC (1995 4th revised edition) Nutrient Requirements of Laboratory Animals. Washington DC: National Academy of Science;1995. p. 14.
• Emery P. Metabolic changes in malnutrition. Eye 2005;19:1029-1034. DOI: 10.1038/sj.eye.6701959.
• Jacobi SK, Moeser AJ, Blikslager AT, Rhoads JM, Corl BA, Harrell RJ, Odle J. Acute effects of rotavirus and malnutrition on intestinal barrier function in neonatal piglets. World J Gastroenterol. 2013;19(31):5094-5102. DOI: 10.3748/wjg.v19.i31.5094
• Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95(2):351-358. DOI: 10.1016/0003-2697(79)90738-3
• Beutler E, Durgun O, Kelly BM. Improved method for the determination of blood glutathione. J Lab Clin Med. 1963 May 51:882-888.
• Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem. 1951;193(1):265-275.
• Chandra RK. Protein-energy malnutrition and immunological responses. J Nutr. 1992;122(3 Suppl):597-600.
• Mello AS, de Oliveira DC, Bizzarro B, Sá-Nunes A, Hastreiter AA, Beltran JS, Xavier JG, Borelli P, Fock RA. Protein malnutrition alters spleen cell proliferation and IL-2 and IL-10 production by affecting the STAT-1 and STAT-3 balance. Inflammation 2014;37(6):2125-2138. DOI: 10.1007/s10753-014-9947-5
• Santoso D, Sudiana K, Yunus M. The effect of a low protein diet on the expression of IL-6, TNF-α and TGF-β in the kidney tissue of mice model. Malaysian J Med Health Sci. 2019;15(1):46-52.
• Guzik TJ, Touyz RM. Oxidative stress, inflammation, and vascular aging in hypertension. Hypertension 2017;70(4):660-667. DOI: 10.1161/HYPERTENSIONAHA.117.07802
• Borelli P, Blatt S, Pereira J, de Maurino BB, Tsujita M, de Souza AC, Xavier JG, Fock RA. Reduction of erythroid progenitors in protein-energy malnutrition. Br J Nutr. 2007;97(2):307-314. DOI: 10.1017/S0007114507172731
• Cortés-Barberena E, Ceballos-Olvera I, González-Márquez H, Ortiz-Muñiz R. Moderate and severe malnutrition alters proliferation of spleen cells in rats. Cell Prolif. 2013;46(2):164-171. DOI: 10.1111/cpr.12019
• El-Hodhod MAA, Nassar MF, Zaki MM, Moustafa A. Apoptotic changes in lymphocytes of protein energy malnutrition patients. Nutr Res. 2005;25(1):21-29.
• Mainali ES, McMurray DN. Protein deficiency induces alterations in the distribution of T-cell subsets in experimental pulmonary tuberculosis. Infect Immun. 1998;66(3):927-931. DOI: 10.1128/IAI.66.3.927-931.1998
• Betancourt M, Ortíz R, González C. Proliferation index in bone marrow cells from severely malnourished rats during lactation. Mutat Res. 1992;283(3):173-177. DOI: 10.1016/0165-7992(92)90104-p.
• Santos EW, Oliveira DC, Silva GB, Tsujita M, Beltran JO, Hastreiter A, Fock RA, Borelli P. Hematological alterations in protein malnutrition. Nutr Rev. 2017;75(11):909-919. DOI: 10.1093/nutrit/nux041.
• Jungermann K. Functional heterogeneity of periportal and perivenous hepatocytes. Enzyme 1986;35(3):161-180. DOI: 10.1159/000469338
• Monk JM, Woodward B. Elevated blood interleukin-10 levels and undiminished systemic interleukin-10 production rate prevail throughout acute protein-energy malnutrition in the weanling mouse. Cytokine 2009;47(2):126-131. DOI: 10.1016/j.cyto.2009.05.015
• Lykke M, Hother AL, Hansen CF, Friis H, Mølgaard C, Michaelsen KF, Briend A, Larsen T, Sangild PT, Thymann T. Malnutrition induces gut atrophy and increases hepatic fat infiltration: Studies in a pig model of childhood malnutrition. Am J Transl Res. 2013;5(5):543-554.
• Sylura OG, Richard L. Sideroblastic anemies, iron deficiency and iron- deficiency anemia. Lee GR, Wintrobe MM, editors. Wintrobe’s Clinical Hematology.19th edition. Philadelphia London: Tea & Febigem; 1993. p.852-872.
• Beutler E. Anemi resulting from other nutritional deficiencies. Kaushansky K, Lichtman MA, Beutler E, Kipps TJ, Seligsohn U, Prchal JT, editors. Williams Hematology. 8th ed. USA: McGraw-Hill; 2006. P.555-559.
• El-Nawawy A, Barakat S, Elwalily T, Abdel-Moneim Deghady A, Hussein M. Evaluation of erythropoiesis in protein energy malnutrition. East Mediterr Health J. 2002;8(2-3):281-289.
• Shiner M, Redmond AO, Hansen JD. The jejunal mucosa in protein-energy malnutrition. A clinical, histological, and ultrastructural study. Exp Mol Pathol. 1973;19(1):61-78. DOI: 10.1016/0014-4800(73)90041-5
• Miguel Parra O, Hernandez-Blasquez J, de Sousa e Silva RA, da Silva JR, Peduto L, Maltauro Soares M, Abrão Saad W, Abrão Saad W Jr. Reduction of liver mass due to malnutrition in rats. Correlation with emaciation of animals and size of organs not inserted in the portal system. Sao Paulo Med J. 1995;113(3):903-909. DOI: 10.1590/s1516-31801995000300004
• Santos MJS, Canuto KM, de Aquino CC, Martins CS, Brito GAC, Pessoa TMRP, Bertolini LR, de Sá Carneiro I, Pinto DV, Nascimento JCR, da Silva BB, Valença JT Jr, Guedes MIF, Owen JS, Oriá RB. A Brazilian regional basic diet-induced chronic malnutrition drives liver inflammation with higher ApoA-I activity in C57BL6J mice. Braz J Med Biol Res. 2020;53(6):e9031. DOI: 10.1590/1414-431x20209031
• Etukudo M, Agbedana O, Akang E, Osifo B. Biochemical changes and liver tissue pathology in weanling Wistar albino rats with protein-energy malnutrition (PEM). Afr J Med Med Sci. 1999;28(1-2):43-47.
• Bourke CD, Berkley JA, Prendergast AJ. Immune dysfunction as a cause and consequence of malnutrition. Trends Immunol. 2016;37(6):386-398. DOI: 10.1016/j.it.2016.04.003
• de Queiroz CA, Fonseca SG, Frota PB, Figueiredo IL, Aragão KS, Magalhães CE, de Carvalho CB, Lima AÂ, Ribeiro RA, Guerrant RL, Moore SR, Oriá RB. Zinc treatment ameliorates diarrhea and intestinal inflammation in undernourished rats. BMC Gastroenterol. 2014 Aug;14:136. DOI: 10.1186/1471-230X-14-136
• Mocellin S, Marincola F, Rossi CR, Nitti D, Lise M. The multifaceted relationship between IL-10 and adaptive immunity: Putting together the pieces of a puzzle. Cytokine Growth Factor Rev. 2004;15(1):61-76. DOI: 10.1016/j.cytogfr.2003.11.001
• Dewan P, Kaur IR, Faridi MMA, Agarwal KN. Cytokine response to dietary rehabilitation with curd (Indian dahi) & leaf protein concentrate in malnourished children. Indian J Med Res. 2009;130(1):31-36.
• Rana S, Gupta D, Malik A, Katyal R, Mehta SK. Mild-to-moderate malnutrition and small intestine of young rhesus monkeys. Nutrition. 1995;11(3):292-295.
• Reddy JK, Rao MS. Lipid metabolism and liver inflammation. II. Fatty liver disease and fatty acid oxidation. Am J Physiol Gastrointest Liver Physiol. 2006;290(5):G852-858. DOI: 10.1152/ajpgi.00521.2005