Efeitos da restrição proteica perinatal sobre o balanço oxidativo no hipotálamo de ratos de 60 dias de idade
Palavras-chave:
Hipotálamo, Estresse oxidativo, Desnutrição proteico-calóricaResumo
Objetivo
Avaliar os efeitos da restrição proteica materna sobre o estresse oxidativo no hipotálamo de ratos de 60 dias de idade.
Métodos
Ratos Wistar machos foram divididos em dois grupos experimentais de acordo com a dieta da mãe durante a gestação e lactação: grupo controle (NP: 17% caseína n=6) e grupo desnutrido (LP: 8% caseína n=6). Aos 60 dias de vida, os ratos foram sacrificados para coleta do hipotálamo para posterior análise bioquímica.
Resultados
Os resultados demonstraram aumento do estresse oxidativo no grupo desnutrido, observado através do aumento do conteúdo de cabonilas (p=0,0357) e redução da atividade da enzima glutationa-S-transferase (p=0,0257) e da capacidade antioxidante não enzimática, evidenciada pela queda da razão glutationa reduzida/glutationa oxidada (p=0,0406) e dos níveis de tióis totais (p=0,0166).
Conclusão
Uma dieta com baixo teor de proteínas durante a gestação e lactação está intimamente associada ao aumento do estresse oxidativo e à redução da capacidade antioxidante no hipotálamo de ratos de 60 dias de vida.
Referências
Gluckman PD, Hanson MA, Mitchell MD. Developmental origins of health and disease: reducing the burden of chronic disease in the next generation. Genome Med. 2010;2(14).
Lillycrop KA, Burdge GC. Epigenetic mechanisms linking early nutrition to long term health. Best Pract Res Clin Endocrinol Metab. 2012;26:667-76.
Hales CN, Barker DJP. The thrifty phenotype hypothesis: Type 2 diabetes. Br Med Bull. 2001;60:5-20.
Lee HS. Impact of Maternal Diet on the Epigenome during In Utero Life and the Developmental Programming of Diseases in Childhood and Adulthood. Nutrients. 2015;7:9492-507.
Wang G, Walker SO, Hong X, Bartell TR, Wang X. Epigenetics and early life origins of chronic noncommunicable diseases. J Adolesc Health. 2013;52:14-21.
Fall CHD. Fetal programming and the risk of noncommunicable disease. Indian J Pediatrics. 2013;80:13-20.
Silva PAA, Bernardo EM, Pereira AR, Andrade SSC, Lima TA, Moura FC, et al. Moderate offspring exercise offsets the harmful effects of maternal protein deprivation on mitochondrial function and oxidative balance by modulating sirtuins. Nutr Metab Cardiovasc Dis. 2021;31(5):1622-34.
Ferreira DJS, Pedroza AA, Braz GRF, Fernandes MP, Lagranha CJ. Mitochondrial dysfunction: maternal protein restriction as a trigger of reactive species overproduction and brainstem energy failure in male offspring brainstem. Nutr Neurosci. 2019;22(11):778-88.
Pedroza A, Ferreira DS, Santana DF, Silva PT, Aguiar JF, Sellitti D, et al. A maternal low-protein diet and neonatal overnutrition result in similar changes to glomerular morphology and renal cortical oxidative stress measures in male Wistar rats. Appl Physiol Nutr Metab. 2019;44(2):164-71.
Roseboom T, Rooij S, Painter R. The Dutch famine and its long-term consequences for adult health. Early Hum Dev. 2006;82(8):485-91.
Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol. 2003;552:335-44.
Salim S. Oxidative Stress and the Central Nervous System. J Pharmacol Exp Ther. 2017;360(1):201-05.
Santana DF, Ferreira DS, Braz G, Sousa S, Silva T, Gomes DA, et al. Maternal Protein Restriction in Two Successive Generations Impairs Mitochondrial Electron Coupling in the Progeny’s Brainstem of Wistar Rats From Both Sexes. Front Neurosci. 2019;13(203).
Ferreira DS, Liu Y, Fernandes MP, Lagranha CJ. Perinatal low-protein diet alters brainstem antioxidant metabolism in adult offspring. Nutr Neurosci. 2016;19(8):369-75.
Ferreira DJS, Silva PAA, Braz GRF, Silva-Filho RC, Lima TA, Fernandes MP, et al. Mitochondrial bioenergetics and oxidative status disruption in brainstem of weaned rats: Immediate response to maternal protein restriction. Brain Res. 2016;1642:553-61.
Bouret SG. Nutritional programming of hypothalamic development: critical periods and windows of opportunity. Int J Obes Suppl. 2012;2:19-24.
Nascimento L, Freitas CM, Silva-Filho R, Leite AC, Silva AB, Silva AI, et al. The effect of maternal low-protein diet on the heart of adult offspring: role of mitochondria and oxidative stress. Appl Physiol Nutr Metabol. 2014;39:880-7.
Reeves PG, Nielsen FH, Fahey JR, George C. AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr. 1993;123(11):1939-51.
Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of proteindye binding. Anal Biochem. 1976;72:248-54.
Draper HH, Squires EJ, Mahmoodi H, Wu J, Agarwal S, Hadley M. A comparative evaluation of thiobarbituric acid methods for the determination of malondialdehyde in biological materials. Free Radic Biol Med. 1993;15:353-63.
Reznick AZ, Packer L. Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Methods Enzymol. 1994;233:357-63.
Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem. 1972;247:3170-5.
Aebi H. Catalase in vitro. Methods Enzymol. 1984;105:121-6.
Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem. 1974;249:7130-9.
Hissin PJ, Hilf R. A fluorometric method for determination of oxidized and reduced glutathione in tissues. Anal Biochem. 1976;74:214-26.
Braz GRF, Emiliano AS, Sousa SM, Pedroza AAS, Santana DF, Fernandes MP, et al. Maternal low-protein diet in female rat heart: possible protective effect of estradiol. J Dev Orig Health Dis. 2017;8:322-30.
Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959;82:70-7.
Halliwell B, Gutteridge JM. Free radicals in biology and medicine. Oxford: United Kingdom; 2007.
Breton C, Lukaszewski MA, Risold PY, Enache M, Guillemot J, Rivière G, et al. Maternal prenatal undernutrition alters the response of POMC neurons to energy status variation in adult male rat offspring. Am J Physiol Endocrinol Metab. 2009;296:E462-E472.
Palou M, Priego T, Sánchez J, Palou A, Picó C. Sexual dimorphism in the lasting effects of moderate caloric restriction during gestation on energy homeostasis in rats is related with fetal programming of insulin and leptin resistance. Nutr Metab. 2010;7:e69.
Manuel-Apolinar L, Rocha L, Damasio L, Tesoro-Cruz E, Zarate A. Role of prenatal undernutrition in the expression of serotonin, dopamine and leptin receptors in adult mice: Implications of food intake. Mol Med Rep. 2014;9:407-12.
Fernandes MS, Pedroza AA, Andrade Silva SC, Lemos MDT, Bernardo EM, Pereira AR, Santos TM, Lagranha C. Undernutrition during development modulates endoplasmic reticulum stress genes in the hippocampus of juvenile rats: Involvement of oxidative stress. Brain Res. 2022;23:1797.
Fragoso J, Carvalho JSG, Silva HT, Loizon E, Oliveira NSV, Vidal H, et al. Effects of maternal low-protein diet and spontaneous physical activity on the transcription of neurotrophic factors in the placenta and the brains of mothers and offspring rats. J Dev Orig Health Dis. 2021;12(3):505-12.
Kalsbeek A, Scheer FA, Perreau-Lenz S, La Fleur SE, Yi CX, Fliers E, et al. Circadian disruption and SCN control of energy metabolism. FEBS Lett. 2011;585(10):1412-26.
Crossland RF, Balasa A, Ramakrishnan R, Mahadevan SK, Fiorotto ML, Van den Veyver IB. Chronic Maternal Low-Protein Diet in Mice Affects Anxiety, Night-Time Energy Expenditure and Sleep Patterns, but Not Circadian Rhythm in Male Offspring. Plos One. 2017;12(1).
Feoli AM, Siqueira IR, Almeida L, Tramontina AC, Vanzella C, Sbaraini S, et al. Effects of protein malnutrition on oxidative status in rat brain. Nutrition. 2006;22:160-5.
Torres N, Bautista CJ, Tovar AR, Ordaz G, Rodriguez-Cruz M, Ortiz V, et al. Protein restriction during pregnancy affects maternal liver lipid metabolism and fetal brain lipid composition in the rat. Am J Physiol Endocrinol Metab. 2010;298:E270-7.
Stadtman ER, Van RH, Richardson A, Wehr NB, Levine RL. Methionine oxidation and aging. Biochim Biophys Acta. 2005;1703:135-40.
Singhal SS, Singh SP, Singhal P, Horne D, Singhal J, Awasthi S. Antioxidant role of glutathione S-transferases: 4-Hydroxynonenal, a key molecule in stress-mediated signaling. Toxicol Appl Pharmacol. 2015;289:361-70.
Awasthi YC, Ansari GA, Awasthi S. Regulation of 4-hydroxynonenal mediated signaling by glutathione S-transferases. Methods Enzymol. 2005;401:379-407.
Gajewska B, Kazmierczak B, Kuzma-Kozakiewicz M, Jamrozik Z, Baranczyk-Kuzma A. GSTP1 polymorphisms and their association with glutathione transferase and peroxidase activities in patients with motor neuron disease. CNS Neurol Disord Drug Targets. 2015;14(10):1328-33
Circu ML, Aw TY. Glutathione and modulation of cell apoptosis. Biochim Biophys Acta. 2012;1823(10):1767- 77.
Halliwell B. Oxidative stress and neurodegeneration: where are we now? J Neurochem. 2006;97(6):1634-58.
Sousa SM, Braz GRF, Freitas CM, Santana DF, Sellitti DF, Fernandes MP, et al. Oxidative injuries induced by maternal low-protein diet in female brainstem. Nutr Neurosci. 2018;21(8):580-8.
Braz GRF, Emiliano AS, Sousa SM, Pedroza AAS, Santana DF, Fernandes MP, et al. Maternal low-protein diet in female rat heart: possible protective effect of estradiol. J Dev Orig Health Dis. 2017;8(3):322-30.
Downloads
Publicado
Como Citar
Edição
Seção
Licença
Copyright (c) 2023 Deyvison Guilherme Martins SILVA, Jonata Henrique de SANTANA, Thyago de Oliveira RODRIGUES, Elenilson Maximino BERNANDO, Anderson Apolonio da Silva PEDROZA, Cláudia Jacques LAGRANHA
![Creative Commons License](http://i.creativecommons.org/l/by/4.0/88x31.png)
Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.