Oxidative stress and angiogenesis in primary hyperparathyroidism

Abstract

SummaryBackgroundThe inappropriate elevation of parathormone (PTH), which regulates the process of angiogenesis in parathyroid tissue, causes the changes of activity of enzymes responsible for the removal of free radicals. Parathyroidectomy (PTX) in patients with primary hyperparathyroidism (PHPT) lowers the level of PTH and leads to the reduction of risk of cardiovascular and all-cause mortality by normalization of the antioxidant status. Therefore, the aims of the study were to assess the activity of antioxidant enzymes and free radical reaction products in patients after parathyroidectomy, and to evaluate the correlation between the systemic oxidative stress and angiogenic parameters.Materials and methodsPatients with PHPT treated surgically were enrolled into the study. Total antioxidant capacity (TAC), total oxidative status (TOS), oxidative stress index (OSI), superoxide dismutase (SOD), ceruloplasmin (CER), lipid hydroperoxides (LHP) and malondialdehyde (MDA) were measured before and after parathyroidectomy. The immunohistological expression of angiogenic factors in parathyroid specimens was assessed by the BrightVision method from ImmunoLogic using murine monoclonal anti-human: anti-VEGF, anti-CD31 and anti-CD106 antibodies.ResultsThe significant increase of TAC, CER, reduction of TOS, MDA, SOD, especially for cytoplasmic form, and significant decrease of OSI, LHP were observed after PTX. There was no significant correlation between changes of oxidative stress markers and angiogenic parameters: VEGF, CD-31, CD-106 in parathyroid tissue. The correlation level was low and medium.ConclusionsParathyroidectomy causes down-regulation of lipid peroxidation processes and leads to reduction of oxidative stress in patients with PHPT. The decrease in the OSI is the results of down-regulation of oxidative stress in the postoperative period. The change of the antioxidant status has no impact on angiogenesis processes in parathyroid tissue.

Parathyroid Hormone Causes Endothelial Dysfunction by Inducing Mitochondrial ROS and Specific Oxidative Signal Transduction Modifications

“…Among the candidate mechanisms able to induce endothelial dysfunction, we chose to investigate the role of ROS since the presence in literature of indirect evidence about the relation between PTH levels and markers of oxidative stress [22, 23]. We found that PTH induces mitochondrial ROS production in a calcium-dependent manner.…”

“…Several mechanisms contribute to endothelial dysfunction, and among these, the oxidative stress seems to have a determinant role; indeed, sustained ROS production can inactivate nitric oxide (NO), thus contributing to impaired endothelial-dependent vasodilatation [20]. The potential regulation of ROS production by PTH has been hypothesized [21], since after parathyroidectomy in patients, the decrease of oxidative stress markers occurs [22, 23]. However, a mechanistic link between PTH and altered redox balance is still to be verified.…”

Effects of Qingshen Granules on the Oxidative Stress‐NF/kB Signal Pathway in Unilateral Ureteral Obstruction Rats

“…Malondialdehyde (MDA) is a common lipid peroxidation product and reflects the level of ROS produced by lipid oxidation, which, in turn, indirectly reflects the degree of oxidative damage in tissues and cells. Therefore, SOD and MDA are commonly used to evaluate the level of oxidative stress in cells [ 27 ]. It could be shown that the internal oxidation became unbalanced as the level of blood Scr rose.…”

Vascular endothelial growth factor-mediated peritoneal neoangiogenesis in peritoneal dialysis

“…Oxidative stress-induced angiogenesis has been well established and its intermediate regulatory medium is VEGF. 50,51 Combet et al confirm an independent contribution of uremia in the peritoneal changes during PD, especially for peritoneal neoangiogenesis, with increased levels of peritoneal nitric oxide synthase (NOS) isoform, AGEs and VEGF from a rat model of subtotal nephrectomy. 52 Enhanced NOS activity and endothelial NOS up-regulation are considered as a reasonable explanation for peritoneal morphologic changes (angiogenesis and increased endothelial area), which are based on the biologic relevance between NOS and vascular density.…”