Decrease In Retinol Research Articles

Vitamin and microelement supply of adolescent girls with menstrual function disorders

Objective — to identify the relationship between changes in the concentration of vitamins A, E, D, magnesium content, and comorbid pathology in adolescent girls with menstrual function disorders. Materials and methods. Examinations involved 237 girls with menstrual function disorders aged 11—18 years. Oligomenorrhea (OM) was diagnosed in 103 patients, and abnormal uterine bleeding (AUB) in 134 girls. Results and discussion. Comorbid pathology was revealed in most patients, regardless of the type of menstrual function disorder. Endocrine system disorders were the most frequent comorbidities. In girls with OM, comorbid endocrine disorders were accompanied by a decrease in the levels of vitamins A (pu < 0.01) and E, due to decrease in the frequency of their elevated indicators (pφ < 0.03). At the same time, mostly normal magnesium levels were registered (pφ < 0.001) due to a decrease in the frequency of its reduced and elevated levels compared to patients without pathology. In girls with AUB, comorbid endocrine system pathology was accompanied by decrease in the frequency of optimal levels of 25(OH)D3 (pφ < 0.03), and comorbid pathology of the neuro-­psychiatric sphere was accompanied by decrease in the frequency of elevated levels of vitamins A (pφ < 0.01) and E (pφ < 0.03) compared to girls without pathology. Regardless of the type of menstrual disorder, the greatest number of changes in the vitamin status were found in girls with comorbid pathology of the endocrine system. In patients with OM, the retinol levels were lower than in girls with AUB (pφ < 0.01), and a decrease in tocopherol levels was observed (pφ > 0.05). In girls with AUB, elevated levels of vitamin A (pφ < 0.03), vitamin E (pφ < 0.04), and moderate vitamin D deficiency (pφ < 0.03) were more frequently registered compared to girls with OM. Vitamin D deficiency in girls with abnormal uterine bleeding was less frequently registered compared to patients with oligomenorrhea (pφ < 0.05). It should be noted that comorbid pathology of the digestive system in abnormal uterine bleeding was mostly often accompanied by the decreased tocopherol levels (pφ < 0.05) and normal magnesium values (pφ < 0.04) compared to patients with oligomenorrhea. Conclusions. The study revealed a correlation between fluctuations in the content of vitamin status components and comorbid pathology in girls with menstrual disorders. The most pronounced changes in oligomenorrhea were found under conditions of concomitant pathology of the endocrine system, while in abnormal uterine bleeding, they were identified in the presence of endocrine disorders and disturbances in the neuro­psychiatric sphere. The combination of oligomenorrhea and endocrine pathology, as well as abnormal uterine bleeding and nervous disorders, is accompanied by a decrease in retinol and tocopherol reserves, creating conditions for the deterioration of compensatory­adaptive reactions of the body by suppressing the low-­molecular-­weight link of the antioxidant defense system. Abnormal uterine bleeding and concomitant endocrine disorders are associated with more pronounced moderate vitamin D deficiency.

Levels of retinol and retinoic acid in pancreatic cancer, type-2 diabetes and chronic pancreatitis.

Retinoids participate in multiple key processes in the human body e.g., vision, cell differentiation and embryonic development. There is growing evidence of the relationship between retinol, its active metabolite- all-trans retinoic acid (ATRA) - and several pancreatic disorders. Although low levels of ATRA in pancreatic ductal adenocarcinoma (PDAC) tissue have been reported, data on serum levels of ATRA in PDAC is still limited. The aim of our work was to determine serum concentrations of retinol and ATRA in patients with PDAC, type-2 diabetes mellitus (T2DM), chronic pancreatitis (CHP) and healthy controls. High performance liquid chromatography with UV detection (HPLC) was used to measure serum levels of retinol and ATRA in 246 patients with different stages of PDAC, T2DM, CHP and healthy controls. We found a significant decrease in the retinol concentration in PDAC (0.44+/-0.18 mg/L) compared to T2DM (0.65+/-0.19 mg/L, P<0.001), CHP (0.60+/-0.18 mg/L, P< 0.001) and healthy controls (0.61+/-0.15 mg/L, P<0.001), significant decrease of ATRA levels in PDAC (1.14+/-0.49 ug/L) compared to T2DM (1.37+/-0.56 ug/L, P<0.001) and healthy controls(1.43+/-0.55 ug/L, P<0.001). Differences between early stages (I+II) of PDAC and non-carcinoma groups were not significant. We describe correlations between retinol, prealbumin and transferrin, and correlation of ATRA and IGFBP-2. Significant decrease in retinol and ATRA levels in PDAC compared to T2DM, healthy individuals and/or CHP supports existing evidence of the role of retinoids in PDAC. However, neither ATRA nor retinol are suitable for detection of early PDAC. Correlation of ATRA levels and IGFBP-2 provides new information about a possible IGF and retinol relationship.

Neurodegenerative disease and antioxidant biomarkers: A bidirectional Mendelian randomization study.

Previous observational studies have suggested that antioxidant imbalance is correlated with neurodegenerative diseases, while its cause-effect remains unclear. Thus, the goal of the present study is to explore the causal relationship between 11 antioxidant biomarkers and 3 most common neurodegenerative diseases [Alzheimer's disease (AD), Amyotrophic Lateral Sclerosis (ALS) and Parkinson's disease (PD)]. A bidirectional Mendelian randomization (MR) study was performed to investigate the causal effects by using 3 main methods (Variance Weighted (IVW), Weighted Median (WM), and MR-Egger regression) in the European population. The data of 11 antioxidant biomarkers were obtained from the open database by the most up-to-date Genome-Wide Association Studies (GWAS), the summary statistics of PD and ALS were obtained from the International Parkinson's Disease Genomics Consortium (IPDGC) (33,674 cases, and 449,056 controls), and the International Amyotrophic Lateral Sclerosis Genomics Consortium (IALSC) (20,806 cases and 59,804 controls), respectively. For AD, we specifically used two recently published GWAS data, one from the International Genomics of Alzheimer's Project (IGAP) (21,982 cases and 41,944 controls), and the other from a large meta-analysis (71,880 cases and 383,378 controls) as validation data. Based on the Bonferroni correction p < 0.0015, there was no significant causal evidence for the antioxidant biomarkers on neurodegenerative diseases, however, the reverse analysis found that AD was significantly related to the decrease in retinol (IVW: beta = -0.023, p = 0.0007; WM: beta = -0.025, p = 0.0121), while the same analysis was carried out between the AD validation database and retinol, the results were consistent (IVW: beta = -0.064, p = 0.025). Moreover, AD on Glutathione S-transferase (GST), PD on Glutathione Peroxidase (GPX) as well as PD on uric acid (UA) also indicated potential causal-and-effect associations (IVW: p = 0.025; p = 0.027; p = 0.021, respectively). There was no sufficient evidence that antioxidant imbalance has a significant causal effect on neurodegenerative diseases. However, this study revealed that genetically predicted AD was significantly related to the decrease in retinol, which provides a new insight into previous research and indicates the possibility to regard retinol as potential biomarker for the diagnosis and progress of AD.

SUPPLY OF THE ORGANISM WITH VITAMIN A UNDER CONDITIONS OF DIETARY PROTEIN DEFICIENCY AND TOXIC INJURY WITH ACETAMINOPHEN IN RATS

The paper presents studies of the content of retinol and retinyl esters in the liver and serum of rats under conditions of acetaminophen-induced lesions and alimentary protein deficiency. During the experiment, the animals consumed a semi-synthetic diet of AIN-93. Simulation of acute toxic damage was carried out by per os administration of acetaminophen to rats at the rate of 1250 mg/kg of animal weight. It was found that under the simulated experimental conditions – protein deficiency and toxic damage by acetaminophen – there is a decrease in retinol in the serum of rats with minimal values when entering the body of medicinal xenobiotics, regardless of the amount of dietary protein. An increase in the content of retinoids (retinol and retinyl esters) has been reported in the liver of rats under the conditions of alimentary protein deprivation, which is probably aimed at maintaining the level of vitamin A in the blood. Toxicity with acetaminophen, regardless of dietary protein intake, is a key factor in reducing retinol and retinyl esters levels in rat liver. Under conditions of consumption of a low-protein diet in the body of rats, redistribution of retinoids occurs: an increase in the content of retinol and its storage forms in the liver with a simultaneous decrease in the level of retinol in the blood serum can probably be considered as a prerequisite for the mobilization of vitamin A into the bloodstream.

The state of redox processes and of antiradical protection system in patients with stomach cancer

The state of redox processes and reducing synthesis in patients with gastric cancer and criteria of important diagnostic indices of early metabolic disorders specific for the development of gastrocancerogenesis have been investigated. The results showed a significant increase in the activity of lactate dehydrogenase, glucose-6-phosphate dehydrogenase, malate dehydrogenase and a reduced activity of succinate dehydrogenase and isocitrate dehydrogenase indicating changes in the glycolysis functioning, pentose phosphate pathway and TCA cycle. The study of non-enzymatic link of the antioxidant system revealed a decrease in retinol, α-tocopherol and increase in uric acid in the serum of patients with gastric cancer. The analysis showed that the patients with the first stage of tumor development in all cases had at least 2 times reduced water soluble vitamins in blood. It allows making a suggestion that oncopathology is formed on the background of a serious metabolic dysfunction and vitamin deficiency.

Decline in plasma retinol in unconjugated hyperbilirubinemia treated with bilirubin adsorption using an anion-exchange resin.

When an anion-exchange resin column (Plasorba BR-350) was used for the treatment of unconjugated hyperbilirubinemia, we found an unexpected decrease in plasma retinol (vitamin A) concentrations in a patient with type I Crigler-Najjar syndrome. The purpose of our study was to investigate the mechanism of this decrease in plasma retinol. When the patient's serum bilirubin exceeded the bilirubin binding capacity of 14.7 mumol bilirubin/g serum albumin (i.e., 720 mumol/L of bilirubin), abrupt deterioration of the patient's neurologic status (suppression in his gait and speech) occurred, so the need to apply plasmapheresis to reduce the unconjugated bilirubin was indicated. Blood was drawn from the radial artery at a flow rate of 160 mL/min and pumped into a membrane plasma separator at a rate of 40 mL/min. The plasma was passed through the bilirubin adsorbent column and returned to the venous blood line of the plasma separator. Plasma samples were taken at the inlet and outlet of the bilirubin adsorbent column before and after treatment. The concentration of unconjugated bilirubin in plasma was effectively reduced by the perfusion, but plasma retinol was coincidentally decreased by the perfusion to vitamin A deficiency levels. The patient's plasma retinol was 2,127 nmol/L at the beginning of therapy and decreased to 1,492 nmol/L after repeated adsorption treatments. As the amounts of decrease in retinol (912 +/- 123 nmol/L) after the perfusion were almost equal to those in retinol-binding protein (1,010 +/- 192 nmol/L), retinol may have been removed as a form of holo retinol-binding protein. Decreases in retinol and retinol-binding protein levels were also observed in low-density lipoprotein (LDL) apheresis with a dextran sulfate column (i.e., a cation-exchange resin column). In the patient with Crigler-Najjar syndrome, retinol taken dietarily was removed by plasmapheresis. However, the patient manifested no clinical symptoms associated with vitamin A deficiency, since his liver storage of retinol could supply the loss caused by plasmapheresis treatment. We should measure plasma retinol concentrations to evaluate the loss of retinol during plasmapheresis treatment coupled with an anion-exchange resin column.

Decreases in retinol and retinol-binding protein during total parenteral nutrition in rats are not due to a vitamin A deficiency

Perfusion feeding in rats induced a decrease in circulating retinol despite an adequate supply of vitamin A. We studied the effect of total parenteral nutrition (TPN) on the retinol specific carrier in rat, analyzing holo-RBP (bound to retinol) and apo-RBP (without retinol) in serum and in liver. Vitamin A-sufficient (A+) and -deficient (A-) rats were characterized in terms of vitamin A and RBP status and then perfused (TPN-A+ and TPN-A-) or orally pair-fed (O-A+ and O-A-) with vitamin A. In A+ rats, a decrease in serum retinol (2.6-fold) and an increase in apo-RBP was concomitant with a massive accumulation of RBP in the liver. In TPN-A rats, both circulating RBP and liver total RBP were decreased. In TPN-A+ rats, there was a decrease in circulating retinol (2.4-fold) in parallel to a decrease of serum and liver RBP protein and mRNA. We provide evidence that infused retinyl palmitate was not responsible for serum retinol and RBP decrease and that retinol depletion was not due to vitamin A deficiency. Whatever the vitamin A status, TPN may induce in rats a down-regulation of hepatic RBP synthesis, which may, at least partially, explain the alteration of retinol and RBP in serum.

Vitamin A metabolism in rats chronically treated with 3,3′,4,4′,5,′-hexabromobiphenyl

Chronic dietary administration of 3,3′,4,4′,5,5′-hexabromobiphenyl (HBB), 1 mg/kg diet, caused a decrease in retinol (20-fold) and retinyl esters (23-fold) in the livers of female rats, but resulted in a 6.4-fold increase in retinol and 7.4-fold increase in retinyl esters in the kidneys. Liver acyl-CoA: retinol acyltransferase and retinyl palmitate hydrolase activities were reduced while serum concentration of retinol was unaffected by HBB feeding. Metabolism of a physiological dose of [11- 3H]retinyl acetate (10 μg), was examined in rats fed either vitamin A-adequate diet, or marginal amounts of vitamin A, or vitamin A-adequate diet containing HBB. A 13-fold greater amount of the administered vitamin A was found in kidneys of HBB-treated rats. In rats fed adequate or low amounts of vitamin A, kidney radioactivity was primarily in the retinol fraction, while in HBB-fed rats the radioactivity was associated mostly with retinyl esters. Fecal and urinary excretion of radioactivity was greatly increased in HBB-treated rats. Chronic HBB feeding results in a loss of ability of liver to store vitamin A, and severely alters the uptake and metabolism of vitamin A in the kidneys. We conclude that HBB causes major disturbances in the regulation of vitamin A metabolism.