Oxidative stress, NOx/l-arginine ratio and glutathione/glutathione S-transferase ratio as predictors of 'sterile inflammation' in patients with alcoholic cirrhosis and hepatorenal syndrome type II.

Continuous intake of alcohol leads to liver cirrhosis because of imbalance of oxidative stress/antioxidative defense and chronic 'sterile inflammation'. Hepatorenal syndrome (HRS) is the most severe complication of liver cirrhosis. The aim of our study was to assess: (1) the oxidative stress/antioxidative defense markers such as malondialdehyde (MDA), oxidative glutathione (GSH) and glutathione S-transferase (GST), (2) inflammation [C-reactive protein (CRP)], and (3) nitrate/nitrite levels (NOx) and its substrate L-arginine level. The study enrolled three groups: a group with cirrhosis and HRS (48 patients), a group with cirrhosis without HRS (32 patients), and a control group (40 healthy blood donors). All the patients with cirrhosis and HRS had type II HRS. MDA concentration was significantly higher in the groups with cirrhosis with and without HRS. Significant positive correlation was documented between the MDA level and de Ritis coefficient (AST/ALT), a marker of liver damage severity; between MDA and inflammation (CRP); between MDA and NOx concentration in the groups with cirrhosis with and without HRS. The correlation between MDA and creatinine level was significant in the group with HRS. The levels of GSH and GST were significantly lower in the groups with cirrhosis with and without HRS. The results of the study revealed that an increase in MDA and NOx concentration, along with decreased values of antioxidative defense and L-arginine, may indicate that liver damage can have an influence on progression to renal failure.

Sequential analysis of oxidative stress markers and vitamin C status in acute bacterial osteomyelitis.

In bacterial bone infections, excessively formed oxidants may result in local and systemic oxidative stress. Vitamin C is the major extracellular nonenzymatic antioxidant, also implicated in bone cells metabolism and viability. The physiological functions of vitamin C largely depend on its redox status. We sequentially assessed oxidative stress markers, hydroperoxides and malondialdehyde (MDA), total antioxidant activity (AOA), total vitamin C, ascorbic acid (Asc), and oxidized/reduced vitamin C ratio in 137 patients with acute osteomyelitis (OM). Compared to 52 healthy controls, in OM group baseline serum hydroperoxides, MDA and oxidized/reduced vitamin C ratio were higher whilst Asc and AOA were lower (P < 0.05, resp.). On the other side, total vitamin C levels in patients and controls were similar (P > 0.05), thereby suggesting a relative rather than absolute vitamin C deficiency in OM. During the follow-up, oxidative stress markers, AOA, and oxidizedreduced vitamin C ratio were gradually returned to normal, while there was no apparent change of total vitamin C concentrations. Persistently high values of oxidized/reduced vitamin C ratio and serum MDA were found in subacute OM. In conclusion, acute OM was associated with enhanced systemic oxidative stress and the shift of vitamin C redox status towards oxidized forms.

Optic Neuritis in a Patient with Seropositive Myelin Oligodendrocyte Glycoprotein Antibody During the Post-COVID-19 Period.

Reports of neuro-ophthalmological manifestations and complications in patients with coronavirus disease 19 (COVID-19) are still scarce. The aim of this article is to present optic neuritis, as possible post-infectious manifestation of COVID-19. Four weeks after hospitalization for seropositive coronavirus disease 19 (COVID-19), presented as bilateral bronchopneumonia, with radiology and laboratory findings also pointed to high clinical suspicion to COVID-19, a 63-year-old man developed a headache and subacute and profound visual loss on his right eye. The disease presentation was the right eye papillitis. Inflammatory parameters were normal at the time of hospitalization, and IgM and IgG for SARS-CoV-2 were still positive. After corticosteroid pulse therapy, his vision improved significantly and on follow-up visits returned to normal. All laboratory and radiology findings were unremarkable, except for antibodies against SARS-CoV-2 and myelin oligodendrocyte glycoprotein (MOG). We discuss about capacity of SARS-CoV-2 to cause optic neuritis and possible significance of MOG antibodies in similar cases.

The Monitoring of Protein Markers of Inflammation and Serum Lipid Concentration in Obese Subjects with Metabolic Syndrome.

BACKGROUND: Obesity is one of the most common modern health problems worldwide. Proinflammatory cells accumulate in the adipose tissue of the obese, and the presence of a low level chronic inflammation in obesity is associated with the emergence of a range of metabolic disorders in cluding cardiovascular disease, insulin resistance, type-2 diabetes, fatty-liver disease, and others. Neutrophils are early parti - cipants in inflammatory processes. After the appropriate stimu lation, these cells release reactive oxygen and nitrogen species, which leads to degranulation and secretion of myeloperoxidase and other enzymes. Myelo per oxidase and its reactive oxidants contribute to tissue damage during inflammatory processes in the human body. METHODS: The study included 175 subjects who were, in com - pliance with the International Diabetes Federation criteria, divided into 3 groups: normal weight subjects (N=106), subjects with abdominal obesity (N=37) and the third group consisted of subjects with the metabolic syndrome (N=32). RESULTS: By analyzing the myeloperoxidase enzyme activity (kU/L), and the levels of high-sensitivity C-reactive protein in the blood of all subjects, we detected their significantly higher activity and levels in subjects with the metabolic syndrome, as compared to normal weight subjects (p<0.001). CONCLUSIONS: Based on our results, we can conclude that the MPO activity in the serum progressively increases with obesity and the metabolic syndrome, which indicates that this prooxidant enzyme may play a role in the pathophysiological mechanisms of the obesity and the metabolic syndrome related complications.

Role of Myeloperoxidase in Patients with Chronic Kidney Disease.

Chronic kidney disease (CKD) is a worldwide public health problem. Patients with CKD have a number of disorders in the organism, and the presence of oxidative stress and systemic inflammation in these patients is the subject of numerous studies. Chronic inflammation joined with oxidative stress contributes to the development of numerous complications: accelerated atherosclerosis process and cardiovascular disease, emergence of Type 2 diabetes mellitus, development of malnutrition, anaemia, hyperparathyroidism, and so forth, affecting the prognosis and quality of life of patients with CKD. In this review we presented the potential role of the myeloperoxidase enzyme in the production of reactive/chlorinating intermediates and their role in oxidative damage to biomolecules in the body of patients with chronic kidney disease and end-stage renal disease. In addition, we discussed the role of modified lipoprotein particles under the influence of prooxidant MPO intermediates in the development of endothelial changes and cardiovascular complications in renal failure.

Xanthine Oxidase Activity in Type 2 Diabetes Mellitus Patients with and without Diabetic Peripheral Neuropathy.

This study investigated the relationship between serum xanthine oxidase (XOD) activity and the occurrence of diabetic peripheral neuropathy (DPN) in type 2 diabetes mellitus (T2DM) patients. Serum XOD activity, ischemia-modified albumin (IMA), uric acid (UA), albumin, glycated hemoglobin (HbA1c), advanced glycation end products (AGE), total free thiols, atherogenic index of plasma (AIP), and body mass index (BMI) were measured in 80 T2DM patients (29 with and 51 without DPN), and 30 nondiabetic control subjects. Duration of diabetes, hypertension, medication, and microalbuminuria was recorded. Serum XOD activities in controls, non-DPN, and DPN were 5.7 ± 2.4 U/L, 20.3 ± 8.6 U/L, and 27.5 ± 10.6 U/L (p < 0.01), respectively. XOD activity was directly correlated to IMA, UA, BMI, HbA1c, and AGE, while inversely correlated to serum total free thiols. A multivariable logistic regression model, which included duration of diabetes, hypertension, AIP, HbA1c, UA, and XOD activity, revealed HbA1c [OR = 1.03 (1.00-1.05); p = 0.034] and XOD activity [OR = 1.07 (1.00-1.14); p = 0.036] as independent predictors of DPN. Serum XOD activity was well correlated to several other risk factors. These results indicate the role of XOD in the development of DPN among T2DM patients.

Predictive value of serum myeloperoxidase activity for thrombosis of arteriovenous fistulas.

Myeloperoxidase is a proinflammatory protein that appears as a result of increased oxidative stress. It plays an important role in the promotion and progression of atherosclerosis. The aim of this study was to determine the importance of MPO as a predictive parameter for thrombosis of arteriovenous fistula (AVF). The study involved monitoring patients with AVFs for hemodialysis over a period of 2 years. There were 41 patients, 19 (46%) men and 22 (54%) women, with mean age of 65 ± 12.7 years. Routine laboratory analyses were carried out in all respondents, including determination of MPO concentration. Gender, demographic and anthropometrical characteristics, smoking, alcohol consumption, as well as the presence of diabetic nephropathy, as an etiological factor of kidney disease, were recorded. The group of patients who developed initial thrombosis of the AVFs had significantly different values for leukocytes (8.5 ± 3.8 vs. 7.3 ± 2.1, P = 0.024), erythrocytes (2.8 ± 0.27 vs. 3.2 ± 0.65; P = 0.019), hemoglobin (88.5 ± 81 vs. 99.1 ± 6.02; P = 0.041), and myeloperoxidase (19.3 ± 4.67 vs. 11.1 ± 4.43; P = 0.007) when compared with the group without fistula thrombosis. Diabetic nephropathy (P = 0.02) characterized the group of patients with thrombosis of the fistula. Diabetic nephropathy (B = 2.53, P = 0.049) and MPO (B = 0.03, P = 0.029) were statistically significant predictors of fistula thrombosis. In our study, MPO and diabetic nephropathy were predictors of thrombosis of the AVF.

The role of xanthine oxidase in hemodialysis-induced oxidative injury: relationship with nutritional status.

The role of xanthine oxidase (XOD) in patients undergoing chronic hemodialysis treatment (HD) is poorly understood. Geriatric nutritional risk index (GNRI) ≤ 90 could be linked with malnutrition-inflammation complex syndrome. This study measured XOD, myeloperoxidase (MPO), superoxide dismutase (SOD), lipid hydroperoxides, total free thiol groups, and advanced oxidation protein products (AOPP) in 50 HD patients before commencing (pre-HD) and immediately after completion of HD session (post-HD) and in 22 healthy controls. Pre-HD serum hydroperoxides, AOPP, XOD, and SOD were higher and total thiol groups were lower in patients than in controls (P < 0.05, resp.). Compared to baseline values, serum MPO activity was increased irrespective of GNRI status. Serum XOD activity was increasing during HD treatment in the group with GNRI ≤ 90 (P = 0.030) whilst decreasing in the group with GNRI > 90 (P = 0.002). In a multiple regression analysis, post-HD serum XOD activity was independently associated with GNRI ≤ 90 ( ß ± SE: 0.398 ± 0.151; P = 0.012) and HD vintage ( ß ± SE: -0.349 ± 0.139; P = 0.016). These results indicate that an upregulated XOD may be implicated in HD-induced oxidative injury contributing to accelerated protein damage in patients with GNRI ≤ 90.

Arteriovenous fistulas and digital hypoperfusion ischemic syndrome in patients on hemodialysis.

AIM: To determine survival parameters as well as characteristics of patients with this syndrome. METHODS: The investigation was conducted over a period of eight years, as a prospective, non-randomized, clinical study which included 204 patients, treated by chronic hemodialysis. Most patients received hemodialysis 12 h per week. As vascular access for hemodialysis all subjects had an arteriovenous fistulae. Based on surveys the respondents were divided into groups of patients with and without digital hypoperfusion ischemic syndrome. Gender, demographic and anthropometric characteristics, together with comorbidity and certain habits, were recorded. During this period 34.8% patients died. RESULTS: Patients with digital hypoperfusion ischemic syndrome were older than those without ischemia (P = 0.01). Hemodialysis treatment lasted significantly longer in the patients with digital hypoperfusion ischemic syndrome (P = 0.02). The incidence of cardiovascular disease (P < 0.001) and diabetes mellitus (P = 0.01), as well as blood flow through the arteriovenous fistula (P = 0.036), were higher in patients with digital hypoperfusion ischemic syndrome. Statistically significant differences also existed in relation to oxygen saturation (P = 0.04). Predictive parameters of survival for patients with digital hypoperfusion ischemic syndrome were: adequacy of hemodialysis (B = -3.604, P < 0.001), hypertension (B = -0.920, P = 0.018), smoking (B = -0.901, P = 0.049), diabetes mellitus (B = 1.227, P = 0.005), erythropoietin therapy (B = 1.274, P = 0.002) and hemodiafiltration (B = -1.242, P = 0.033). Kaplan-Meier survival analysis indicated that subjects with and without digital hypoperfusion ischemic syndrome differed regarding the length of survival (P < 0.001), i.e., patients with confirmed digital hypoperfusion ischemic syndrome died earlier. CONCLUSION: Survival was significantly longer in the patients without digital hypoperfusion ischemic syndrome.

Xanthine oxidase and lens oxidative stress markers in diabetic and senile cataract patients.

Xanthine oxidase (XOD) is a prooxidant enzyme possibly implicated in diabetic lens injury and genesis of senile cataract (SC). We evaluated the impact of diabetes on XOD activity and its relationships with lens oxidative stress markers in patients operated on for SC. Serum and lens XOD activities, lens malondialdehyde (MDA), conjugated dienes, superoxide dismutase (SOD), glutathione peroxidase (GPx) and reduced glutathione (GSH) levels were measured in 62 non-diabetic and 29 diabetic patients operated on for SC. Lens XOD, SOD, GPx and GSH levels were gradually declining, while MDA and serum XOD were increasing with patient's age. Lens XOD activity was positively correlated with conjugated dienes concentration (rho=0.316; p=0.003) while being inversely correlated with age (rho=-0.371; p<0.001), indicating that low ocular expression of XOD could be related to lower intensity of oxidative stress and delayed occurrence of SC. When samples were adjusted for confounding factors, serum XOD (p<0.001), lens XOD (p=0.003) and conjugated dienes (p=0.002) were significantly higher in diabetic than in non-diabetic group. Lens SOD and GPx were moderately increased while MDA and GSH were unchanged in diabetic, compared with non-diabetic SC group. Blood HbA1C concentration was positively correlated with lens XOD (rho=0.346; p<0.001) as well as serum XOD activity (rho=0.485; p<0.001). These results suggest that poor glycemic control may upregulate systemic and ocular XOD activities contributing to lens oxidative stress and possibly to earlier onset of cataract.

Antioxidant capacity of lenses with age-related cataract.

The immediate cause of the occurrence of cataract is unknown, but oxidative damage and effects of reactive oxygen species are considered important in its etiopathogenesis. Our research was aimed at testing the nonenzyme antioxidant power of corticonuclear lens blocks, with different types and different maturity of age-related cataract. Clinical and biochemical researches were carried out in 101 patients with age-related cataract. In corticonuclear lens blocks of the patient, the concentration of nonprotein and total-SH groups and the concentration of total vitamin C and dehydroascorbic acid (DHA) were determined; the current redox balance of dehydroascorbate/ascorbate and total antioxidant power measured by ferric-reducing ability were examined. In corticonuclear lens blocks with incipient cataract a significantly higher concentration of GSH, total SH groups, concentration of total vitamin C and ascorbic acid (AA), and ferric-reducing ability were measured. The measured concentration of DHA is higher than the concentration of AA in the lenses with the incipient and mature cataract. The concentration ratio of redox couple DHA/AA is higher in lenses with mature cataract, where the measured concentration of AA was lower than in the incipient cataract. Timely removal of DHA from the lens is important because of its potential toxicity as an oxidant. An increase of the current concentration of DHA/AA redox balance can be an indicator of oxidative stress.

[Reduced glutathione level and GSH-dependent enzyme activities in corticonuclear blocks of lenses in patients with senile cataract].

INTRODUCTION: Reduced compound glutathione (GSH) in the lens has the function to protect the thiol group of lens proteins, and as a substrate of glutathione peroxidase (GPx) and glutathione S-transferase (GST). Protein containing thiol groups is significant for the normal function of lens epithelium, i.e. enzymes Na-K-ATP-ase, thus influencing cell permeability. The relationship GSH/GSSG (oxidized glutathione) is normally high in the lens and other ocular tissue owing to the glutathione-redox cycle, which is localized in the lens epithelium and cortex surface. OBJECTIVE: The aim of the study was to investigate non-enzymic factors of the antioxidant protection of non-protein and protein tiol, as well as to determine glutathione-dependent enzyme activity in the corticonuclear blocks of lenses in patients with senile cataract. METHODS: Biochemical studies of lens were carried on 101 patients with senile cataract. According to cataract maturity degree, the patients were classified into two groups: senile incipient cataract (N = 41) and mature senile cataract (N = 60). GSH concentration was determined by Ellman's reagent. GPx activity was assayed with cumene hydroperoxide, and that of glutathione S-transferase by follow-up of glutathione conjugation and 1-chloro-2.4-dinitrobenzene rates. RESULTS: A significantly higher GSH concentration was found in the corticonuclear blocks of lenses with initial as related to mature cataract (p < 0.001). The activity of enzyme GPx and GST was considerably higher in the corticonuclear blocks of lenses with initial cataract (p < 0.001). With cataract progression, the quantity of available GSH, necessary for GPx and GST functioning, declined, so that the activity of these enzymes was also significantly decreased in mature cataract. CONCLUSION: The determined lower GSH concentration and antioxidant enzyme activity in corticonuclear blocks of lenses, particularly in cataract with a nuclear component, indicate the weakened antioxidant response of lens tissue during the development of senile cataract.

The effect of exhaustive exercise on oxidative stress generation and antioxidant defense in guinea pigs.

BACKGROUND: Exercise induces a multitude of physiological and biochemical changes in blood that can affect its redox status. Exercise causes an increase in oxygen consumption by the whole body and particularly by the exercising muscle. As a result of this process there is a rise in the production of reactive oxygen species (ROS), which are capable to trigger a chain of damaging biochemical and physiological changes known as lipid peroxidation and oxidative stress. Since the early work of Dillard et al. in 1978, and findings of increased lipid peroxidation following acute aerobic exercise, the topic of exercise-induced oxidative stress has received considerable attention. OBJECTIVES: The aim of this study was to examine how swimming to the point of exhaustion affects oxidative stress generation and nonenzymatic antioxidant activity in an animal model. MATERIAL AND METHODS: The experiments were conducted on 10 male Dunkin-Hartley guinea pigs, and the swimming program used in the study, described as swimming to exhaustion, was defined by Dawson and Horvath. Peripheral blood samples were taken at rest and immediately after the exercise test, and the following parameters were evaluated: total plasma peroxide concentration (TPPC), total plasma thiols (TPT), plasma xanthine oxidase activity (XOD), plasma antioxidant capacity and total plasma proteins. RESULTS: No significant difference was found between TPPC measured at rest and immediately after exercise swimming test (p = 0.138). Two other parameters--TPT and XOD activity--showed significant differences before and after the swimming exercise test: After the test the TPT value decreased significantly (p = 0.022), while XOD activity increased significantly (p = 0.039). Comparing antioxidant activity in plasma before and after the exercise test, although the value decreased, the difference was not statistically significant (p = 0.755). CONCLUSIONS: The results of this study show that exercise to exhaustion induces the generation of oxidative stress primarily by oxidative modification of protein molecules. The results also indicated that the prooxidative enzyme xanthine oxidase is an important source of ROS during exercise-induced oxidative injury.

[Oxidation stress role in age-related cataractogenesis].

INTRODUCTION: Age-related cataract not only diminishes human life quality but it also represents a big impact on healthcare budget of almost every country as the population ages globally. Hence, cataract prevention is a big and true challenge, but a very difficult task to be accomplished. Nowadays cataract is more than a routinely recognized and almost always successfully operated ophthalmologic disease. The diagnosis of age-related cataract diagnosis might alert doctors to some systemic disorders on the whole body level. Increasing age is certainly the most essential age-related cataract risk factor. However, it seems that cataract could be a multifactor disease because of its individual, familiar, racial and gender expression differences. OXIDATION STRESS: Oxidation stress and its form caused by ultraviolet light- photo-oxidative stress--are considered to be crucial in the etiopathogenesis of cataract. All biomolecules suffer damages during cataract formation. On the other side, the lens possess a range of antioxidant elements and mechanisms of their action, which enable long lasting maintenance of lens transparency and functioning. Although they are primary characteristics of the lens, these antioxidant elements also depend on their systemic availability and consumption. This paper is a short literature review of the relation between oxidation stress and age-related cataract.

Oxidative stress and myeloperoxidase activity during bacterial meningitis: effects of febrile episodes and the BBB permeability.

OBJECTIVE: To investigate participation of extracellular myeloperoxidase (MPO) in oxidative stress during different courses of the bacterial meningitis (BM). MATERIALS AND METHODS: We sequentially assessed WBC count, blood-brain barrier (BBB) permeability, serum and cerebrospinal fluid (CSF) lipid peroxidation (LPO), MPO and antioxidative activity (AOA) in proven pediatric BM. RESULTS: BM patients exhibited increased systemic and local LPO and MPO, and reduced AOA, which was exaggerated in the febrile episodes. Serum MPO and LPO products were related to the BBB permeability at the baseline. CSF hydroperoxide level was influenced by the BBB permeability, CSF albumin concentration, and serum hydroperoxide (r=0.502; p<0.001, and r=0.611; p<0.001, and r=0.358; p<0.001, respectively). CSF hydroperoxide and MPO correlated in complicated cases during the study. CONCLUSIONS: These results suggest that CSF LPO and MPO were closely related in BM, had different courses if febrile episodes had occurred, but were partly influenced by the BBB permeability.

[Role of lipid peroxidation in pathogenesis of senile cataract].

BACKGROUND/AIM: Cataract is a structural, biochemical and optical change in the eye lens, which changes transmission and refraction of light rays reducing keenness and clarity of a figure on the retina. Its occurrence is highest in older people, over the age of 65 (45.9%), thus a certain degree of opacification exists practically in all people over the 70. Our research was directed to measuring of lipid peroxidation products in cataract lenses involved in early stages of cataractogenesis through oxidative stress and in the development of mature cataract. METHODS: Clinical and biochemical research was carried out in 101 patients with cataract, 46 women and 55 men. The average age of the group was 72.47 (average = 7.98). According to the cataract maturity degree the patients were classified into two groups as follows: cataracta senilis incipiens (n = 41) and cataracta senilis matura (n = 60). Measuring of diene conjugates was carried out by spectrophotometer. Fluorescent lipid peroxidation products were measured by a spectrofluorophotometer, and malondialdehyde (MDA) concentration was measured by colorimeter as a product of a reaction with thiobarbituric acid (TBA). RESULT: Significantly higher diene conjugated concentration in lenses was measured in the patients with the diagnosis cataracta senilis incipiens (p < 0.001) as well as the intensity of fluorescent iminopropens (p < 0.001). Significantly higher MDA concentration in lens (p < 0.001) was measured in the patients with cataracta senilis matura. CONCLUSION: The lens structure changes caused by lipid peroxidation can, with other risk factors present, influence the occurrence and development of mature cataract. Some cataract types show different lipid peroxidation intensity with the most distinct changes in cataract wich started as corticonuclear.