Cardiac changes in apoptosis, inflammation, oxidative stress, and nitric oxide system induced by prenatal and postnatal zinc deficiency in male and female rats

• Published in: European journal of nutrition Vol. 57; no. 2; pp. 569 - 583
• Main Authors: Juriol, Lorena Vanesa, Gobetto, María Natalia, Mendes Garrido Abregú, Facundo, Dasso, Marina Ercilia, Pineda, Gonzalo, Güttlein, Leandro, Carranza, Andrea, Podhajcer, Osvaldo, Toblli, Jorge Eduardo, Elesgaray, Rosana, Arranz, Cristina Teresa, Tomat, Analía Lorena
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-03-2018; Springer Nature B.V
• Subjects: Animals; Antioxidants; Apoptosis; Biomarkers - blood; Biomarkers - metabolism; Cardiovascular diseases; Chemistry; Chemistry and Materials Science; Coronary Vessels - immunology; Coronary Vessels - metabolism; Coronary Vessels - pathology; Coronary Vessels - physiopathology; Deficiency Diseases - immunology; Deficiency Diseases - metabolism; Deficiency Diseases - pathology; Deficiency Diseases - physiopathology; Diet; Endothelium, Vascular - immunology; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Endothelium, Vascular - physiopathology; Enzymes; Female; Females; Fetal Development; Fetuses; Gene expression; Gene Expression Regulation, Enzymologic; Heart; Heart diseases; Inflammation; Inflammation Mediators - blood; Inflammation Mediators - metabolism; Interleukin 6; Lactation; Male; Maternal Nutritional Physiological Phenomena; mRNA; Myocarditis - etiology; Myometrium - immunology; Myometrium - metabolism; Myometrium - pathology; Myometrium - physiopathology; NAD(P)H oxidase; Nitric oxide; Nitric Oxide Synthase Type III - genetics; Nitric Oxide Synthase Type III - metabolism; Nitric-oxide synthase; Nutrient deficiency; Nutrition; Original Contribution; Oxidative Stress; Phosphorylation; Pregnancy; Random Allocation; Rats, Wistar; Rodents; Superoxide; Thiobarbituric acid; Transforming growth factor-b1; Tumor necrosis factor; Ventricle; Weaning; Zinc - deficiency; Prenatal and postnatal growth; Sex differences; Cardiac apoptosis; Cardiac oxidative stress; Cardiac nitric oxide system; Moderate zinc deficiency
• ISSN: 1436-6207; 1436-6215
• DOI: 10.1007/s00394-016-1343-5

Purpose
Zinc restriction during fetal and postnatal development could program cardiovascular diseases in adulthood. The aim of this study was to determine the effects of zinc restriction during fetal life, lactation, and/or post-weaning growth on cardiac inflammation, apoptosis, oxidative stress, and nitric oxide system of male and female adult rats.
Methods
Wistar rats were fed a low- or a control zinc diet during pregnancy and up to weaning. Afterward, offspring were fed either a low- or a control zinc diet until 81 days of life. IL-6 and TNF-α levels, TUNEL assay, TGF-β1 expression, thiobarbituric acid-reactive substances that determine lipoperoxidation damage, NADPH oxidase-dependent superoxide anion production, antioxidant and nitric oxide synthase activity, mRNA and protein expression of endothelial nitric oxide synthase, and serine1177 phosphorylation isoform were determined in left ventricle.
Results
Zinc deficiency activated apoptotic and inflammatory processes and decreased TGF-β1 expression and nitric oxide synthase activity in cardiac tissue of both sexes. Male zinc-deficient rats showed no changes in endothelial nitric oxide synthase expression, but a lower serine1177 phosphorylation. Zinc deficiency induced an increase in antioxidant enzymes activity and no differences in lipoperoxidation products levels in males. Females were less sensitive to this deficiency exhibiting lower increase in apoptosis, lower decrease in expression of TGF-β1, and higher antioxidant and nitric oxide enzymes activities. A zinc-adequate diet during postnatal life reversed most of these mechanisms.
Conclusion
Prenatal and postnatal zinc deficiency induces alterations in cardiac apoptotic, inflammatory, oxidative, and nitric oxide pathways that could predispose the onset of cardiovascular diseases in adult life.