The Effect of Glutathione on Development and Prognosis in Non-Muscle-Invasive Bladder Cancer.

Background: Glutathione, along with its related enzymes, constitutes a key antioxidant defense mechanism against oxidative stress and cancer formation in the body. Among urological malignancies, bladder cancer ranks second following prostate cancer. Oxidative stress has significant involvement in the development and prognosis of bladder cancer. This investigation aimed to examine the impact of glutathione on prognosis in patients with non-muscle-invasive bladder cancer. Methods: This study included 98 patients with high grade non-muscle-invasive bladder cancer who had undergone intravesical Bacillus Calmette-Guérin therapy and 30 healthy controls with no history of uroepithelial carcinoma of the bladder. The patients with bladder cancer were evaluated in three subgroups. Group 1 consisted of 41 patients who did not experience recurrence during follow-up, Group 2 included 28 patients who had recurrent tumors, and Group 3 consisted of 29 patients who progressed to muscle-invasive stages. Blood samples were collected from all participants. Blood levels of reduced, oxidized, and total glutathione were measured spectrophotometrically. Results: Reduced glutathione levels significantly differed among the groups (p < 0.001), attributed to the control group exhibiting higher reduced glutathione levels compared with Groups 1, 2, and 3 (p < 0.001). There were no significant differences in reduced glutathione levels between Groups 1 and 2, Groups 1 and 3, or Groups 2 and 3 (p > 0.05). Total glutathione levels varied significantly among the groups (p < 0.001), with the control group having higher levels than Groups 1, 2, and 3 (p < 0.001). No significant differences were detected between any of the paired patient groups in terms of total glutathione levels (p > 0.05). Regarding oxidized glutathione levels, the difference was statistically significant (p < 0.001), with the control group showing lower levels than the remaining three groups (p < 0.001). Paired comparisons revealed no significant differences in oxidized glutathione levels (p > 0.05). Conclusions: This study revealed that glutathione had an effect on the emergence of bladder cancer but did not affect its prognosis. Nevertheless, we recommend that future studies with larger bladder cancer patient cohorts should be conducted to comprehensively determine the impact of glutathione on the prognosis of this cancer.

The impact of varying doses of moringa leaf methanolic extract supplementation in the cryopreservation media on sperm quality, oxidants, and antioxidant capacity of frozen-thawed ram sperm.

To increase rams' post-thaw semen quality following cryopreservation, this study used enriched Tris-based diluent with varying amounts of moringa leaf methanolic extract (MLME). The antioxidant activity, total phenolic, and total flavonoid content were all assessed in MLME. The sperm of five healthy Awassi rams were collected, divided into 4 equal aliquots, and diluted [1:5; (v/v)] in Tris-citrate-glucose extender supplemented with 0.48, 0.56, and 0.64 mg MLME/ml or without MLME supplementation (control). The percentages of sperm total motility (STM, %), sperm progressive motility (SPM, %) and viability (V, %), abnormal morphology (AM, %), membrane functional integrity (MFI, %), and acrosome integrity (AI %) were measured. Malondialdehyde (MDA), nitric oxide (NO), ascorbic acid (AA), superoxide dismutase (SOD), glutathione peroxidase (GPx), total cholesterol (TC), low-density lipoproteins (LDL), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), zinc (Zn), and copper (Cu) were measured. The total phenolic gallic acid and flavonoid catechin (equivalent) contents were 19.78 mg/g and 11.94 mg/g, respectively. 2,2-Diphenyl-1-picrylhydrazyl (34.37 mM TE/g) and 2,2'-azino-bis/3-ethylbenzothiazoline-6-sulfonic acid (53.47 mM TE/g) were found in MLME. MLME had a 64.59 mM TE/g ferric-reducing power. In comparison to control, the addition of 0.64 mg/ml MLME to Tris-based extender resulted in the highest (P < 0.001) STM (55.22 ± 0.98), SPM (45.41 ± .70), SV (60.01 ± 1.05), MFI (75.23 ± 0.77), and AI (73.13 ± 0.72) and the lowest (P < 0.001) AM (21.34 ± 0.72) values. In comparison to the control, the addition of 0.56 mg/ml semen extender resulted in lower STM, SPM, SV, MFI, and AI with higher AM percentages. MDA (P = 0.03), NO (P = 0.012), CHO (P = 0.0001), and LDL (P = 0.004) were reduced by 0.64 mg/ml MLME, while AA (P = 0.017) and SOD (P = 0.0001) were elevated. In conclusion, the highest copper (P = 0.006) and lowest zinc concentrations in MLME (0.48 mg/ml extender) deteriorated the post-thaw semen quality, prompting us to suggest the addition of 0.64 mg MLME to rams' Tris-based semen extender.

Oxidant-antioxidant levels in patients with bladder tumours.

PURPOSE: We have aimed to determine whether oxidants-antioxidants play a role in the etiopathogenesis of bladder tumour by measuring their levels in the serums of patients with bladder tumour. MATERIAL METHOD: Thirty patients with bladder tumour with superficial bladder tumour and 27 normal healthy volunteers were included in the study. Four cc of venous blood was taken from these patients and volunteers in the control group and centrifuged at 5000 rpm for 10 minutes and divided into serum and plasma. The activities of xanthine oxidase, glutathione reductase, glutathione-s transferase, reduced glutathione and superoxide dismutase enzymes in serum were then measured spectrophotometrically. FINDINGS: Antioxidant parameters (glutathione-s-transferase, reduced glutathione, superoxide dismutase and glutathione reductase) in the serum of patients with bladder tumours were found statistically significantly lower than control group (p < .05). On the other hand, xanthine oxidase which is an oxidant indicator, was found significantly higher in patients with bladder cancer than control group (p < .05). CONCLUSION: Oxidative stress is effective in the etiopathogenesis of bladder tumour. We, therefore, believe that antioxidants are protective against bladder tumours and will be effective in the treatment of bladder tumours.

Pro-oxidant antioxidant balance in patients with non-alcoholic fatty liver disease.

AIM: We aimed to determine these parameters in patients with non-alcoholic fatty liver disease using pro-oxidant antioxidant balance assay. BACKGROUND: In human, pro-oxidants and antioxidants are normally produced and there is a balance between production and deletion of them. When the balance between oxidants and antioxidants are disrupted oxidative stress occurs. Oxidative stress is known one of the main mechanisms for the development of nonalcoholic fatty liver disease. Many investigations have evaluated some oxidants and/or antioxidant status in these patients. However, studies explaining the antioxidant status and the oxidant burden in these patients are lacking. METHODS: Sera from 35 healthy subjects and 38 patients with non-alcoholic fatty liver disease were recruited. Then, the pro-oxidant burden and the antioxidants capacity were measured by pro-oxidant antioxidant balance assay. RESULTS: There was no significant difference in the mean pro-oxidant antioxidant balance values between the two study groups. The results demonstrated that serum pro-oxidant antioxidant balance values were positively correlated with BMI and age in the patient group. Furthermore, the pro-oxidant antioxidant balance significantly increased in women when compared with men in all participants. CONCLUSION: It demonstrated that increased antioxidant status could be as a response reflecting of the organism to elevated oxidants in NAFLD patients which may lead to unchanged PAB values.

Evaluation of Vitamin D, Vitamin D Binding Protein Gene Polymorphism with Oxidant - Antioxidant Profiles in Chronic Obstructive Pulmonary Disease.

BACKGROUND: The aim was to evaluate the association of plasma 25-hydroxyvitamin D (25-OHD) and vitamin D binding protein (VDBP or Gc-globin) gene polymorphism with oxidant-antioxidant profiles in patients with chronic obstructive pulmonary disease (COPD), and their role as biomarker risk factors in susceptibility and severity of COPD. METHODS: Eighty patients diagnosed with COPD (mild, moderate and severe according to lung function tests; FEV 1%) and 80 healthy controls were included in the study. Serum nitric oxide (NO) and lipid peroxide (LP), plasma reduced glutathione (RGSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) activity, 25-OHD and VDBP polymorphism were analyzed in all subjects. RESULTS: COPD patients had significantly decreased serum NO, plasma SOD, RGSH, GSH-Px, CAT and 25-OHD versus controls, but had significantly increased serum LP. In COPD patients, 25-OHD levels were significantly lower (41.49± 13.65 ng/mL) versus controls, but more lower in severe COPD patients (30.54±9.09 ng/mL; sensitivity 79.2%; spe - cificity 73.2%, p<0.001) versus mild and moderate COPD. VDBP genotypes frequencies were Gc1S-1S=23.8%, Gc1F-1S=28.8%, Gc1F-1F=15%, Gc1S-2=20%, Gc1F-2=11.3% and Gc2-2=1.3%. Also, VDBP variants frequencies were Gc1S=48.1%, Gc1F=35% and Gc2=16.6%. How ever, Gc1F-1S genotypes and Gc1F variants were significantly higher than in controls (10%, 12.5%; p=0.009, p=0.001, respectively). Moreover, in severe COPD patients, Gc1F-1S genotype was significantly higher than in mild COPD (41.7% vs 31.3%, p=0.04). CONCLUSION: COPD patients had significantly lower plasma 25-OHD and were associated with significantly higher VDBP Gc1F-1S genotypes and Gc1F variants frequencies than controls. Low vitamin D levels and VDBP polymorphism may be important as diagnostic risk factors in the susceptibility to and severity of COPD.

Sulfur mustard causes oxidants/antioxidants imbalance through the overexpression of free radical producing-related genes in human mustard lungs.

The aim of this study is to analyze oxidative stress (OS) and changes in expression of reactive oxygen species (ROS) producing-related genes in mustard lungs. Human lung biopsies provided from controls (n=5) and sulfur mustard (SM)-exposed patients (n=6). Changes in expression of dual oxidases (DUOXs), aldehyde oxidase 1 (AOX1), thyroid peroxidase (TPO), myeloperoxidase (MPO) and eosinophil Peroxidase (EPO) were measured using RT(2) Profiler(™) PCR Array. OS was evaluated by determining bronchoalveolar lavage fluids (BALF) levels of total antioxidant capacity (TAC) and malondialdehyde (MDA). Higher TAC value was observed in BALF of controls compared with patients (0.138±0.02683µmol/l vs 0.0942±0.01793µmol/l), whereas a significant increase in MDA concentration was found in patients (0.486±0.04615 nmol/l vs 0.6467±0.05922 nmol/l). All ROS producing-related genes were overexpressed in the order AOX1>MPO>DUOX2>DUOX1>TPO>EPO. Upregulation of these genes may be a reason for overproduction of ROS, oxidants/antioxidants imbalance, OS and respiratory failures in mustard lungs.

Synergistic effects of resveratrol (free and inclusion complex) and sulfamethoxazole-trimetropim treatment on pathology, oxidant/antioxidant status and behavior of mice infected with Toxoplasma gondii.

This study aimed to investigate the synergistic effects of resveratrol and sulfamethoxazole-trimethoprim (ST) on the treatment of mice experimentally infected by Toxoplasma gondii during the chronic phase of the disease considering infection, behavior, and oxidative/antioxidants profile aspects. For the study, 60 mice were initially divided into two groups: uninfected (n = 24) and infected by T. gondii (n = 36). These two groups were later subdivided into other groups and treated with resveratrol (free and inclusion complex containing resveratrol) alone and co-administered with ST: groups A to D were composed by healthy mice and groups E to J were consisted of animals infected by T. gondii (VEG strain). Treatments began 20 days post-infection for 10 consecutive days with oral doses of 0.5 mg kg(-1) of ST (groups B and F), 100 mg kg(-1) of free resveratrol (groups C and G) and inclusion complex of resveratrol (nanoparticles containing resveratrol) (groups D and H), and lastly an co-administration of both drugs (groups I and J). Behavioral tests (memory, anxiety and locomotion) were performed after treatment. Liver and brain fragments were collected to evaluate pathological changes, brain cysts counts, as well as oxidant and antioxidant levels. A reduction on the number of cysts in the brain of animals treated with both drugs combined was observed; there was also reduced number of lesions on both organs. This drug combined effect was also able to reduce oxidative and increase antioxidant levels in infected mice, which might be interpreted as a resveratrol protective effect. In addition, the combination of ST and resveratrol was able to prevent behavioral changes in infected mice. Therefore, the use of co-administration drugs enhances the therapeutic effect acting on a synergic way, reducing the oxidizing effects of the chemical treatment for toxoplasmosis. In addition, resveratrol in inclusion complex when co-administered with ST showed an improved therapeutic effect of ST reducing oxidative damage, liver damage and the number of cysts in the brain of T. gondii infected mice.

Inflammation, oxidative stress and renin angiotensin system in atherosclerosis.

Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with cardiovascular risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. The impairment of the endothelium associated with cardiovascular risk factors creates an imbalance between vasodilating and vasoconstricting factors, in particular, an increase in angiotensin II (Ang II) and a decrease in nitric oxide. The renin-angiotensin system (RAS), and its primary mediator Ang II, also have a direct influence on the progression of the atherosclerotic process via effects on endothelial function, inflammation, fibrinolytic balance, and plaque stability. Anti-inflammatory agents [statins, secretory phospholipase A2 inhibitor, lipoprotein-associated phospholipase A2 inhibitor, 5-lipoxygenase activating protein, chemokine motif ligand-2, C-C chemokine motif receptor 2 pathway inhibitors, methotrexate, IL-1 pathway inhibitor and RAS inhibitors (angiotensin-converting enzyme inhibitors)], Ang II receptor blockers and ranin inhibitors may slow inflammatory processes and disease progression. Several studies in human using anti-inflammatory agents and RAS inhibitors revealed vascular benefits and reduced progression of coronary atherosclerosis in patients with stable angina pectoris; decreased vascular inflammatory markers, improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis. Recent preclinical studies have demonstrated therapeutic efficacy of vitamin D analogs paricalcitol in ApoE-deficient atherosclerotic mice.