Sex-Dependent Regulation of Lipid Metabolism and Oxidative Stress in Cardiovascular-Relevant Tissues: A Porcine Model
Ivona Žura Žaja, Dražen Đuričić, Alicja Kowalczyk, Sara Strelec, Anamaria Ružić, Ana Shek Vugrovečki, Nina Poljičak-Milas, Marko Samardžija, Goran Bačić, Nino Mačešić, Jadranka Pejaković Hlede, Mario Ostović, Sven Menčik, Marko Pećin, Suzana Milinković-TurSex-related differences in lipid metabolism and oxidative stress are recognized as important modulators of cardiovascular physiology, but they are still insufficiently explored in large animal models. This study examined the influence of sex and gonadal status on oxidative stress, lipid metabolism, and hematological parameters in clinically healthy domestic pigs. Twenty sexually mature pigs (10 months old) were divided into four groups: boars, barrows, gilts, and ovariectomized females (n = 5 per group). In serum, the activities of glutathione peroxidase (GSH-Px), glutathione reductase (GSH-RD), total superoxide dismutase (TSOD), gamma-glutamyl transferase (GGT), and lactate dehydrogenase (LDH), together with concentrations of triglycerides, phospholipids, total cholesterol, high-density lipoprotein cholesterol (HDL cholesterol), low-density lipoprotein cholesterol (LDL cholesterol), non-esterified fatty acids (NEFAs), and malondialdehyde (MDA), were determined. In myocardial and liver tissues, antioxidant enzymes, lipid parameters, and MDA were analyzed. Spectrophotometric methods were used for enzyme activities and lipid parameters, while MDA was quantified by high-performance liquid chromatography. Hematological parameters were determined using an automated hematology analyzer, and serum hormone concentrations were measured by chemiluminescent immunoassays. Group-dependent differences were observed, although the relatively small sample size warrants cautious interpretation. In serum, gilts had higher phospholipid, total cholesterol, and HDL cholesterol concentrations, along with the most favorable LDL: HDL ratio, whereas boars showed the least favorable ratio. Lipid peroxidation, assessed by MDA, was lowest in gilts and highest in barrows. In myocardial tissue, gilts showed higher GSH-RD and TSOD activities and lower MDA concentrations than barrows, suggesting potentially stronger antioxidant protection. In the liver, differences were found in cholesterol, triglycerides, and MDA concentrations, with higher cholesterol in barrows, higher triglycerides in boars, and higher MDA in gilts and ovariectomized females. Hematological differences were also evident, with lower leukocyte and lymphocyte counts in gilts and higher platelet count and plateletcrit in barrows and ovariectomized females. Overall, sex and gonadal status were associated with distinct patterns of metabolic and oxidative responses across serum and tissues. Given the small sample size and cross-sectional design, these findings should be interpreted cautiously and as associative rather than causal.