Total Thiol Groups Research Articles

Supplementation of multi‐vitamins, not glutamine alleviate erythrocyte oxidative status in rats with trauma‐hemorrhagic shock and resuscitation

Resuscitation fluid replacement is the major life saving strategy for patients with hemorrhagic shock; however, resuscitation‐induced oxidative stress may lead to systemic inflammation, multiple organ failure (MOF), and even death. Studies showed that reduction of oxidative stress and preservation of ATP production may improve MOF in animals with trauma‐hemorrhagic shock and resuscitation (THR). In addition, glutamine has been considered as a cellular fuel and is the source of glutathione and multi‐vitamins possess antioxidant activity and play important roles in energy metabolism. Therefore, we investigated the effects of single or simultaneous administration of multi‐vitamins and glutamine on antioxidant defense systems, including enzymatic and non‐enzymatic, in the plasma and erythrocytes of THR. Male SD rats were suffered with THR, including a 5 cm midline laparotomy and mean arterial pressure 30 to 35 mmHg for 60 min followed by resuscitation lactate Ringer's (LR) solution with or without L‐alanyl‐L‐glutamine and/or multi‐vitamins. The sham‐operated, parenterally fed rats were included. After infused with continuous, slow rate of LR solutions for 42 hours, the THR rats had significantly decreased red blood cells and hematocrit and increased erythrocyte glutathione (one‐way ANOVA, p<0.05). Intravenous glutamine significantly increased erythrocyte total and protein‐bound thiol groups and plasma TBARS; intravenous multi‐vitamins significantly decreased erythrocyte TBARS; and combination of glutamine and multi‐vitamins significantly decreased erythrocyte TBARS and the ratio of plasma reduced to oxidized glutathione and increased plasma TBARS. In addition, multi‐vitamins was the main factor to decrease plasma total and protein‐bound thiol groups and plasma and erythrocyte TBARS and to increase the ratio of plasma reduced to oxidized glutathione (two‐way ANOVA, p < 0.05). In conclusion, multi‐vitamins, not glutamine, may alleviate erythrocyte oxidative status in trauma‐hemorrhagic shock and resuscitation.Support or Funding InformationNSC 102‐2320‐B‐030‐005‐MY3This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Citicoline protects against lead-induced oxidative injury in neuronal PC12 cells.

Lead is a major environmental pollutant that causes serious adverse effects on biological systems and cells. In this study, we examined the effect of citicoline on lead-induced apoptosis in PC12 cells. The PC12 cells were pre-treated with citicoline and then exposed to lead for 48 h. The effect of citicoline on cell survival was examined by MTT assay. In addition, levels of lipid peroxidation (LPO), total thiol groups, total antioxidant power (TAP), catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) were evaluated. The levels of Bax, Bcl-2, and caspase-3 were also measured, by Western blot analysis. Citicoline significantly increased the cell viability of PC12 cells exposed to lead. Treatment of PC12 cells with lead increased LPO levels, and citicoline effectively decreased LPO. Levels of total thiol groups and TAP, CAT, SOD, and GSH were significantly increased in citicoline-treated PC12 cells compared with the lead-treated group. Citicoline pretreatment significantly reduced Bax expression, and increased the level of Bcl-2 expression. Citicoline also reduced caspase-3 activation in PC12 cells compared with the lead-treated group. Our findings indicate that citicoline exerts a neuroprotective effect against lead-induced injury in PC12 cells through mitigation of oxidative stress and, at least in part, through suppression of the mitochondria-mediated apoptotic pathway.

Sperm matrix metalloproteinase-2 activity increased in pregnant couples treated with intrauterine insemination: a prospective case control study

Matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-9 (MMP9) have an important role in the reproductive system and in the fertilisation process. The aim of this study was to investigate the MMP2 and MMP9 activity in semen and their association with the pregnancy rate, semen parameters and seminal plasma oxidative stress parameters in couples who were treated with intrauterine insemination (IUI). The semen specimens were obtained from 60 men who attended with their spouse for the IUI in the infertility unit. A controlled ovarian stimulation was performed with clomiphene citrate in IUI cycles. Women with positive pregnancies were recorded (n = 29). The results showed the activity of sperm MMP2 and seminal plasma MMP9 was significantly higher in the pregnant group, compared to the non-pregnant group (p < .05). There was a correlation between the sperm MMP2 activity and the total thiol group (TTG) (r = 0.276, p < .05) and the total antioxidant capacity (TAC) of seminal plasma (r = 0.304, p < .05). The sperm MMP9 showed a positive correlation with the seminal plasma TAC (r = 0.330, p < .05) and an inverse correlation with the lipid peroxidation (LP) of seminal plasma (r = –304, p< 0.05). In addition, the seminal plasma MMP2 activity was correlated to sperm viability (r = 0.266, p< .05) and the TTG of seminal plasma (r = 0.298, p < .05). The MMP2 activity in the sperm may be an important factor for determining the pregnancy rate after IUI. Impact statement What is already known on this subject? Previous studies have reported that the fusion between the sperm and zona pellucida required the activity of matrix metalloproteinase 2 (MMP2), whereas the inhibition of MMP2 can significantly decrease the in vitro fertilisation (IVF) rate. What do the results of this study add? This study has identified that the sperm MMP2 activity was significantly higher in the pregnant couples in comparison with the non-pregnant couples, who treated with intrauterine insemination (IUI). The findings showed there was a correlation between sperm MMP2 activity and the total thiol group (TTG) and the total antioxidant capacity (TAC) of the seminal plasma. What are the implications of these findings for clinical practice and/or further research? MMP2 activity in the sperm could influence the IUI outcome and it is an important factor for IUI success.

INFLUENCE OF LASER TREATMENT ON INDICATORS OF FREE-RADICAL OXIDATION AND ANTIOXIDANT PROTECTION IN SECONDARY PYELONEPHRITIS

Relevance. Optimization of the conservative tactics of acute inflammation of the kidney in nephrolithiasis makes it advisable to use non-traditional methods of detoxification low-intensity laser radiation (LILR) in particular. Aim. To evaluate the effectiveness of laser therapy (LT) in the complex correction of acute secondary pyelonephritis (ASP) in patients with single kidney stones according to the basic adaptation criteria of oxidative-antioxidant clinical medicine КЛИНИЧЕСКАЯ МЕДИЦИНА homeostasis of the organism. Materials and methods. Indices of endogenous intoxication (EI), characterizing the oxidative-antioxidant homeostasis of the body in ASP, were studied in 96 patients with nephrolithiasis aged 19 to 40 years. Patients of the comparison group (48 people) underwent basic (according to the standards) treatment aimed at controlling of calculous pyelonephritis. Patients of the main group (48 people) in the traditional conservative therapy from the second day of hospitalization daily received additional LT sessions with apparatus LTA “Uzor-3KS” with a frequency of 0.6 kHz, a power of 1.5 watts within 4 minutes (total for treatment course is eight procedures). The effectiveness of therapy was assessed on the 5th and 9th day of the inpatient stay. Results. It was found that endotoxicosis in non-destructive forms of ASP is caused by the increase in the concentration of malonic dialdehyde of plasma (by 20.3%) and erythrocytes (by 35.5%), decrease in catalase activity (by 14.2%) and the amount of total (by 11.8%) and free (21.1%) thiol groups with a decrease in the detoxification index (DI) by 24,1%. Compared with the baseline therapy (BT), the effectiveness of LT in the complex treatment of ASP in the analyzed parameters of metabolic homeostasis against the background of the increase in catalase capacity from 6.9 to 10.2%, the detoxification index from 5 to 12.5% was 7.5% (on the 5th day) and 17.5% (on the 9th day of treatment). Conclusions. ASP leads to activation of ROS, suppression of antioxidant and catalase activity of blood, reduction of DI, indicating a subcompensated syndrome of EI. Standard therapy contributes to the normalization of ROS and SLA values of body protection and reduces the level of endotoxicosis caused by ASP. Additional inclusion in the complex treatment of LT sessions more significantly normalizes redox metabolic homeostasis and EI parameters, improving the effectiveness of basic therapy.

Protective effect of aminoguanidine against lipopolysaccharide-induced hepatotoxicity and liver dysfunction in rat

Lipopolysaccharide (LPS) as the major component of the outer membrane of Gram-negative bacteria activates macrophages to produce a high level of pro-inflammatory cytokines which is considered as a cause of liver dysfunction. Overproduction of nitric oxide (NO) has been suggested to have a role in hepatic injury. The aim of the present study was to explore the protective effects of aminoguanidine (AG) as inducible nitric oxide synthase (iNOS) inhibitor against LPS -induced liver dysfunction in rat. The animals were divided into five groups: (1) control (2) LPS (3) LPS-AG50, (4) LPS-AG100 and (5) LPS-AG150. LPS (1 mg/kg) was injected for 5 weeks and AG (50, 100 and 150 mg/kg) was administered 30 min before LPS. Drugs were injected intraperitoneally. LPS induced liver dysfunction presented by increasing the serum level of alkaline phosphatase (ALK-P), alanine aminotransferase (ALT), aspartate aminotransferase (AST). Pretreatment with AG restored harmful effects of LPS on liver function. In addition, LPS resulted in hepatotoxicity, accompanied by enhancing the level of interleukin (IL)-6, malondialdehyde (MDA) and nitric oxide (NO) metabolites and decreasing the content of total thiol groups and superoxide dismutase (SOD) and catalase (CAT) activity. Injection of AG before LPS attenuated LPS-induced hepatotoxicity through decreasing the level of IL-6, MDA and NO metabolites and increasing total thiols and SOD and CAT activity. Considering the protective effect of AG which was seen in the present study, it seems that increased levels of NO due to activation of iNOS has a role in LPS-induced hepatic injury.

Protective effects of 5-HT1A receptor antagonist and 5-HT2A receptor agonist on the biochemical and histological features in a rat model of Alzheimer’s disease

Alzheimer’s disease (AD) is a neurodegenerative disorder and neuropathologically characterized by the aggregation of amyloid-beta (Aβ) plaques, neurofibrillary tangles, enhanced oxidative stress and neurodegeneration. Involvement of serotonergic systems in AD has been supposed and it is suggested that serotonin receptors modulation may provide a novel therapeutic target for AD.This study aimed at investigating the protective effect of NAD-299 (the selective 5-HT1A receptor antagonist) and TCB-2 (the potent5-HT2A receptor agonist) on the hippocampal oxidative stress biomarkers and the number of intact neurons in streptozotocin (STZ)-induced Alzheimer's disease in rats.Fifty adult male Wistar rats weighing 250–300 g were divided into five groups: sham, STZ-treated, STZ + NAD-299 (5 μg/1 μl icv), STZ + TCB-2 (5 μg/1 μl icv) and STZ + NAD-299 (5 μg/0.5 μl icv) +TCB-2 (5 μg/0.5 μl icv). At the end of the study, the rats were weighed, then hippocampal oxidative stress markers [total antioxidant capacity (TAC), malondialdehyde (MDA), the total thiol group (TTG), and DNA damage] were measured. In addition, the number of intact neurons in the CA1 area of the hippocampus was determined using hematoxylin and eosin staining.The results showed that icv injection of STZ reduced hippocampal TAC, TTG levels and intact pyramidal cells and increased DNA damage and MDA levels in the hippocampus of STZ-treated rats. Icv administration of NAD-299, TCB-2, and NAD-299+TCB-2 increased TAC and TTG contents and hippocampal intact neurons and reduced hippocampal DNA damage, MDA levels in icv-STZ treated rats. Moreover, there was no significant difference in weight changes among the experimental groups.According to the obtained results, it is suggested that 5-HT1A receptor antagonist (NAD-299) and 5-HT2A receptor agonist (TCB-2) can reduce oxidative stress and neuronal loss in a rat model of AD and may prevent the AD progression.

Hepatoprotective potential and antioxidant activity of Allium tripedale in acetaminophen-induced oxidative damage.

Allium tripedale (A. tripedale) is a species of wild Allium native to northwest Iran that its hepatoprotective effects have not yet been confirmed. This study investigated the effect of A. tripedale plant against acetaminophen (APAP)-induced acute liver damage. After preliminary studies, the A. tripedale methanol fraction (ATMF) was selected for in vivo study. Thirty-six rats were divided into six groups of 6 each and treated by gavage as follows: groups 1 and 2 received normal saline; group 3 received 400 mg/kg of ATMF; and groups 4-6 were treated with 100, 200, and 400 mg/kg of ATMF, respectively. After two consecutive weeks, except groups 1 and 3, rats were administered with an oral single dose of APAP (2 g/kg). After 48 h, blood and liver samples were collected for histological and biochemical examinations. The results showed that APAP caused a significant increase in alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and alkaline phosphatase serum levels, lipid peroxidation (all with P < 0.001) and hepatic nitric oxide (P < 0.01). In addition, APAP led to the depletion of the total antioxidant capacity, total thiol group (both with P < 0.001), and structural alterations in the hepatic tissue. Following administration of ATMF extract, a significant improvement was observed in the functional and oxidative stress markers of hepatic tissue alongside histopathologic changes. In conclusion, the present study showed that the administration of ATMF might prevent hepatic oxidative damage by improving oxidant/antioxidant balance in animals exposed to APAP.

Possible antioxidant mechanism of coenzyme Q10 in diabetes: impact on Sirt1/Nrf2 signaling pathways

Oxidative stress is a major complication in diabetes mellitus. The aim of this study was to investigate potential antioxidant activity of coenzyme Q10 (Co Q10) against hyperglycemia-induced oxidative stress in diabetic rat and unraveling its mechanism of action by focusing on silent information regulator 1 (Sirt1) and nuclear factor E2-related factor 2 (Nrf2) mRNA expression level. Furthermore, the activity of two Nrf2-dependent antioxidant enzymes (superoxide dismutase and catalase) in the liver of diabetic rats was studied. After induction of diabetes in rats using streptozotocin (55 mg/kg), rats were divided into five groups of six each. Groups 1 and 2 (healthy control groups) were injected with isotonic saline or sesame oil; group 3 received Co Q10 (10 mg /Kg /day), group 4, as a diabetic control, received sesame oil; and group 5 was diabetic rats treated with Co Q10. Afterwards, serum and liver samples were collected, and oxidative stress markers, lipid profile, as well as the expression of Sirt1 and Nrf2 genes were measured. Diabetes induction significantly reduced expression level of Sirt1 and Nrf2 mRNAs and also declined catalase, superoxide dismutase activities, and total thiol groups levels in diabetic group in comparison to healthy controls, while a significant increase was found in the levels of malondialdehyde and lipid profile. Co Q10 treatment significantly up-regulated Sirt1 and Nrf2 mRNA levels along with an increase in catalase activity in diabetic group as compared with untreated diabetic rats. Furthermore, Co Q10 caused a marked decrease in malondialdehyde levels and significantly improved lipid profile. Our data demonstrated that Co Q10 may exert its antioxidant activity in diabetes through the induction of Sirt1/Nrf2 gene expression.

Thymoquinone Prevents Myocardial and Perivascular Fibrosis Induced by Chronic Lipopolysaccharide Exposure in Male Rats: - Thymoquinone and Cardiac Fibrosis.

ObjectivesThymoquinone (TQ) is one of the active ingredients of herbal plants such as Nigella sativa L. (NS) which has beneficial effects on the body. The beneficial effects of TQ on the cardiovascular system have reported. This study aimed to investigate the effect of TQ on cardiac fibrosis and permeability, serum and tissue concentration of inflammatory markers and oxidative stress status in chronic lipopolysaccharide exposure in male rats.MethodsSeventy male Wistar rats were randomly divided into five groups as follows: (1) control; (2) LPS (1 mg/kg/day); (3–5) LPS + TQ with three doses of 2, 5 and 10 mg/kg (n=14 in each group). After 3 weeks, serum and cardiac levels of IL-1β, TNF-α and nitric oxide (NO) metabolites, and cardiac levels of malondialdehyde (MDA), total thiol groups, catalase (CAT) and superoxide dismutase (SOD) activities, permeability of heart tissue (evaluated by Evans blue dye method) and myocardial fibrosis were determined, histologically.ResultsLPS administration induced myocardial and perivascular fibrosis and increased cardiac oxidative stress (MDA), inflammatory markers and heart permeability, while, reduced anti-oxidative enzymes (SOD and CAT) and the total thiol group. Administration of TQ significantly attenuated these observations.ConclusionTQ improved myocardial and perivascular fibrosis through suppression of chronic inflammation and improving oxidative stress status and can be considered for attenuation of cardiac fibrosis in conditions with chronic low-grade inflammation.

Protective Role of Ce Nanoparticles Against the Hepatotoxicity Induced by Exposure to Paraquat

Objectives: The present study aimed to investigate the antioxidant activity of cerium oxide nanoparticles (CeNPs) against paraquat (PQ)-induced liver injury in rats. Methods: Thirty-two male rats were divided into four 8-member groups and treated intraperitoneally with PQ and/or CeNPs for 14 days. Group 1 received PQ (5 mg/kg/d), group 2 received CeNPs (15, 30, and 60 mg/kg/d), group 3 received a combination of PQ (5 mg/kg/d) and CeNPs (15, 30, and 60 mg/kg/d), and group 4 (control group) received saline solution. Serum samples along with liver tissue samples were collected from all the rats. Oxidative stress (OS) biomarkers including total antioxidant capacity, lipid peroxidation, total thiol groups, DNA damage, and nitric oxide levels were determined. Histological samples were also analyzed using hematoxylin and eosin staining slides. Results: Levels of oxidative stress and hepatic tissue damage were significantly higher in the PQ group compared to the control group. CeNPs at a dose of 15 mg/kg showed the antioxidant activity and compromised the PQ-induced damage. Conclusion: In the scenario tested in this study, CeNPs could reduce the levels of OS, as well as hepatic damage induced by PQ.

Extract from Aronia melanocarpa L. Berries Prevents Cadmium-Induced Oxidative Stress in the Liver: A Study in A Rat Model of Low-Level and Moderate Lifetime Human Exposure to this Toxic Metal.

The study investigated, in a rat model of low-level and moderate environmental exposure to cadmium (Cd; 1 or 5 mg Cd/kg diet, respectively, for 3 to 24 months), whether the co-administration of 0.1% extract from Aronia melanocarpa L. berries (AE) may protect against oxidative stress in the liver and in this way mediate this organ status. The intoxication with Cd, dose- and duration-dependently, weakened the enzymatic antioxidative barrier, decreased the concentrations of reduced glutathione and total thiol groups, and increased the concentrations of oxidized glutathione, hydrogen peroxide, xanthine oxidase, and myeloperoxidase in this organ. These resulted in a decrease in the total antioxidative status, increase in the total oxidative status and development of oxidative stress (increased oxidative stress index and malondialdehyde concentration) and histopathological changes in the liver. The administration of AE at both levels of Cd treatment significantly improved the enzymatic and nonenzymatic antioxidative barrier, decreased pro-oxidant concentration, and protected from the development of oxidative stress in the liver and changes in its morphology, as well as normalized the serum activities of liver enzymes markers. In conclusion, consumption of aronia products may prevent Cd-induced destroying the oxidative/antioxidative balance and development of oxidative stress in the liver protecting against this organ damage.

Cardioprotective effect of levosimendan against homocysteine-induced mitochondrial stress and apoptotic cell death in H9C2

Levosimendan is a cardiac inotropic and vasodilator agent that has been reported to have anti-oxidative, anti-inflammatory, and smooth muscle vasodilatory properties. The purpose of this study was to examine the effect of levosimendan on homocysteine-induced cardiomyocyte injury and to explore its underlying mechanisms. H9C2 myocardial cells were incubated with levosimendan 30 min before exposure to homocysteine (Hcy) for 24 h. The effect of levosimendan on cell viability was assessed using the MTT assay. Biological markers of oxidative stress were examined by assessment of lipid peroxidation (LPO), total antioxidant power (TAP), and total thiol groups. Moreover, the expression of caspase-3, Bcl-2, and Bax proteins was determined by western blot analysis. These results showed that levosimendan increased survival of cardiomyocytes in Hcy condition. Treatment with levosimendan decreased lipid peroxidation level. It also enhanced the TAP and total thiol groups. Further, levosimendan pretreatment upregulated the expression of Bcl-2 and downregulated the expression of Bax. The experiments also demonstrated that levosimendan could decrease the expression and activity of caspase-3, which is a key factor in regulating apoptosis. Taken together, these results indicated that levosimendan protects H9C2 myocardial cells against Hcy-induced oxidative stress and apoptosis by scavenging free radicals and modulating the mitochondrial-mediated apoptotic signaling pathway.

Differential expression of heat shock proteins and activation of mitogen‐activated protein kinases in A549 alveolar epithelial cells exposed to cigarette smoke extract

What is the central question of this study? What is the effect of cigarette smoke on cell death, oxidative damage, expression of heat shock proteins (HSPs) and activation of mitogen-activated protein kinases (MAPKs) in A549 alveolar epithelial cells? What is the main finding and its importance? Cigarette smoke induces cytotoxicity and oxidative damage to A549 cells, increases expression of different HSPs and activates MAPK signalling pathways. This could be related to inflammatory response and apoptosis observed in lungs of patients with smoking-related diseases. Cigarette smoking is one of the main risk factors for development of chronic obstructive pulmonary disease (COPD). We previously reported that cigarette smoke (CS) induces damage to proteins and their ineffective degradation. Here, we hypothesize that CS could induce oxidative stress and cytotoxicity in lung epithelial cells through alterations of heat shock protein (HSP) expression and mitogen-activated protein kinase (MAPK) signalling pathways. We exposed A549 alveolar epithelial cells to various concentrations of cigarette smoke extract (CSE). Higher concentrations of CSE caused apoptosis of A549 cells after 4h, while after 24h cell viability was decreased, and lactate dehydrogenase in cell culture medium was increased as well as the number of necrotic cells. Concentrations of malondialdehyde (MDA) were elevated, while total thiol groups were decreased. Changes in the expression of HSPs (HSP70, HSP32 and HSP27) were time-dependent. After 6h, CSE caused an increase in the expression of HSP70 and HSP32, while after 8h all examined HSPs were up-regulated and remained increased up to 48h. Treatment of A549 cells with CSE stimulated phosphorylation of extracellular signal-regulated kinase and p38 in a dose-dependent manner, while c-Jun N-terminal kinase activation was not detected. By using specific inhibitors, we demonstrated that MAPKs and HSPs interplay in CSE effects. In conclusion, our results show that MAPKs and HSPs are involved in the mechanism underlying CSE-induced cytotoxicity and oxidative damage to A549 alveolar epithelial cells. These processes could be related to inflammatory response and apoptosis observed in lungs of patients with smoking-related diseases, such as COPD.

Immunomodulatory properties of captopril, an ACE inhibitor, on LPS-induced lung inflammation and fibrosis as well as oxidative stress.

The role of angiotensin converting enzyme inhibitors on the inflammation process has been demonstrated previously. In the present study, the effects of captopril on lung injury induced by lipopolysaccharide (LPS) were investigated. Control, LPS, 12.5, 25 and 50mg/kg captopril-treated before LPS administration and captopril 50mg/kg before saline administration groups of rats were studied. Total and percentage of differential WBC, the levels of MDA, total thiol groups, the activities of SOD and CAT, the levels of IFN-γ, PGE2, TGF-β1 and IL-4 in the BALF were evaluated. MDA concentration in LPS groups treated with all captopril concentrations, total WBC in LPS + Cap50, percent of neutrophils in LPS + Cap25 and LPS + Cap50, levels of IFN-γ, PGE2, TGF-β1 in LPS + Cap50 and IFN-γ/IL-4 ratio in LPS + Cap25 and LPS + Cap50 were significantly decreased but total thiol groups and activity of SOD in LPS + Cap25 and LPS + Cap50, percent of lymphocyte, CAT activity and concentration of IL-4 only in LPS + Cap50 group were increased in comparison to the LPS group (p < 0.05 to p < 0.001). Captopril dose dependently improved oxidant-antioxidant biomarkers, the imbalance between pro-inflammatory and anti-inflammatory cytokines and showed specific immunomodulatory effect on Th1/Th2 balance in the BALF of lung injury induced by LPS.

Effects of insulin-loaded chitosan-alginate nanoparticles on RAGE expression and oxidative stress status in the kidney tissue of rats with type 1 diabetes.

Objective(s):Chronic hyperglycemia leads to activation of the advanced glycation end products (AGE)-receptor (RAGE) for AGE axis and oxidative stress, which promote diabetic renal damage. This study examines the effect of insulin-loaded trimethyl chitosan nanoparticles on the kidney tissue of diabetic rats. Materials and Methods:Twenty-five male Wistar rats were randomly divided into 5 groups: normal control (C), diabetic group without treatment (DM), diabetic group treated with chitosan-based nanoparticle (DM+NP, 1 ml by gavage), diabetic group treated with 8 IU/kg insulin-loaded trimethyl chitosan nanoparticles (DM+N.in, 1 ml by gavage), and diabetic group treated with 8 IU/kg trade insulin (DM+SC.in, 0.2 ml by subcutaneous injection). The animals were treated from weeks 8 to 10. At the end of the study, serum urea, creatinine, and uric acid were measured. Also, the level of AGE and RAGE mRNA expression, and oxidative stress markers were studied in the kidney tissue.Results:Insulin-loaded nanoparticles similar to trade insulin could significantly reduce urea, creatinine, and uric acid parameters, while the elevated total antioxidant capacity (TAC), thiol groups, and catalase activity also reduced total oxidant status (TOS) and malondialdehyde (MDA) levels (P<0.05). However, the reduction in AGE and RAGE mRNA expression is not statistically significant in both treatments. Of course, the influence of insulin-loaded trimethyl chitosan nanoparticles on the amelioration of all these parameters is higher compared to that of the injected form. No markedly significant differences were observed between these two kinds of treatments. Conclusion:This data reveals that insulin-loaded trimethyl chitosan nanoparticle is a better therapeutic approach than injected insulin.

Antioxidative effect of flavonoid naringenin in the lenses of type 1 diabetic rats.

Oxidative stress arising during diabetes may lead to cataract formation. Thus, in order to prevent oxidative stress development, antioxidants could be considered helpful agents. Naringenin, a flavonoid with a well-documented antioxidative activity, can be found in many plant-derived products, especially citrus fruits. The aim of the study was to examine the effect of naringenin on oxidative stress markers in the lenses of type 1 diabetic rats. The study was conducted on 3-month-old male Wistar rats with streptozotocin-induced type 1 diabetes. The rats were treated orally with naringenin at the doses of 50 and 100 mg/kg for 4 weeks. In the lenses obtained from the animals, enzymatic and non-enzymatic parameters connected with oxidative stress were measured. The enzymatic parameters included superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase activity. For non-enzymatic parameters, the total thiol groups, reduced and oxidized glutathione, protein carbonyl groups, advanced oxidation protein products, malondialdehyde and vitamin C level were assayed. Oral administration of naringenin counteracted most of the unfavorable changes induced by diabetes, including reduction of elevated antioxidative enzymes activity and amelioration of oxidative damage in proteins and lipids. Naringenin administered orally reduces oxidative stress markers in the lenses of type 1 diabetic rats.

Silver Nanoparticles Synthesized Using Eysenhardtia polystachya and Assessment of the Inhibition of Glycation in Multiple Stages In Vitro and in the Zebrafish Model

The aim was to investigate the inhibitory activities on AGE formation by testing silver nanoparticles fabricated using a methanol extract of Eysenhardtia polystachya (EP–AgNPs) and characterized using various physicochemical techniques. The in vitro glucose-albumin assay was used, and cell viability was carried out in RAW264.7 cells. For In vivo testing, we induced diabetes in adult zebrafish with by providing a high blood glucose concentration. EP–AgNPs showed an absorption peak at 413 nm in the UV–Vis spectrum, indicating surface plasmon resonance of the nanoparticles. TEM indicated that most of the particles were spherical, with a diameter of 10–12 nm, a polydispersity index of 0.197, and a zeta potential of − 32.25 mV, suggesting high stability of the nanoparticles. The biocompatible nature of the EP–AgNPs was demonstrated in RAW264.7 cells. EP–AgNPs markedly reduced the formation of AGEs, Amadorin-product/fructosamine, Ne-(carboxymethyl)-lysine, amyloid cross β-structure, and protein carbonyl content in BSA-glucose system and increased total thiol-group after 4 weeks in hyperglycemic zebrafish, EP–AgNPs provided a protective effect against glycation. Data suggest that the inhibitory activity of EP–AgNPs on formation of AGEs is developed through a multiple-stage mechanism of glycation. EP–AgNPs could therefore be an antiglycation agent for prevention diabetic complications.

Captopril Attenuates Diazinon-Induced Oxidative Stress: A Subchronic Study in Rats.

Diazinon (DZN) is an organophosphate pesticide commonly used for pest control in agriculture. It may engender a variety of negative effects in non-target species, including humans and animals. The objective of the present study was to evaluate the ameliorative properties of captopril (CAP), as a thiol containing an angiotensin-converting enzyme inhibitor, against DZN-induced oxidative stress. Twenty-eight male Wistar rats were divided randomly into 4 groups. All the rats were treated orally via gavage once a day for 7 weeks: control (corn oil), CAP (10 mg/kg), DZN (10 mg/kg), and CAP+DZN combination (as mentioned above). Oxidative stress indices in blood serum, liver and kidney homogenates (malondialdehyde [MDA], total thiol groups, and total antioxidant capacity), and erythrocyte hemolysis (superoxide dismutase [SOD] and glutathione peroxidase) were evaluated. Statistical analysis was performed using GraphPad Prism software, version 6.0 (GraphPad, San Diego, CA, USA), by ANOVA, followed by the Tukey post hoc analysis. The MDA content and SOD activity increased significantly in the DZN group compared with those in the control group. Treatment with CAP in the DZN-exposed group significantly decreased (P<0.05) the MDA concentration and the SOD activity. The total thiol groups were decreased in the DZN group and elevated again by CAP treatment. The co-administration of CAP and DZN was able to attenuate lipid peroxidation and enzyme changes caused by DZN.

The effects of mid- and long-term endurance exercise on heart angiogenesis and oxidative stress.

Objective(s):Long-term, irregular endurance exercise may result in disturbance to the angiogenesis of heart muscles and blood supply. The aim of the present study is to evaluate the effects of mid- and long-term endurance exercise on the process of angiogenesis.Materials and Methods:Eighteen male Wister rats of 220±10 g, were randomly assigned to three groups of 6 rats including: Control, Mid, and Long Group. After the training sessions, the rats were weighed and sacrificed.Results:In comparison to the Control Group, the both groups, indicated remarkable increase in the weight of heart and significantly higher serum LDH and CK activity (P<0.01). In addition, after the training sessions, weakened antioxidant heart system (TAC, total thiol groups, and GPX activity) and increased oxidative stress markers (MDA and NO) were remarkably observed in Mid Group and particularly in those in the Long Group in comparison to the Control Group (P<0.05). Finally, significant increase in VEGF-B, MEF-2C and MMP-2 gene expression was found for both experimental groups, associated with the up-regulation of ANGPT-1 and HDAC4 in the Mid Group (P<0.05). While the longer exercise period induced significantly upper VEGF-B, MEF-2C, and MMP-2 and significantly lower ANGPT-1 and HDAC4 in the Long Group (P<0.05). Conclusion:In this study, higher oxidative status and upper angiogenic gene expression with higher VEGF-B, MEF-2c, and MMP-2 and lower ANGPT-1 and HDAC4 were traced as effects of long-term endurance exercise. These results point to the dis-regulation of blood supply in the presence of angiogenesis resulting from long-term exercise.

Oxidative stress in electrohypersensitivity self‑reporting patients: Results of a prospective invivo investigation with comprehensive molecular analysis.

A total of 32 electrohypersensitivity (EHS) self-reporting patients were serially included in the present prospective study for oxidative stress and antioxidative stress response assessment. All thiobarbituric acid-reactive substances (TBARs) were measured in the plasma, particularly malondialdehyde (MDA) for lipid peroxidation; additional measurements included total thiol group molecules, reduced glutathione (GSH), oxidized glutathione (GSSG) for oxidative stress assessment and nitrotyrosine, a marker of peroxynitrite-induced oxidative/nitrosative stress. In addition, the activity of Cu-Zn superoxide dismutase (SOD1) was measured in red blood cells (RBCs) and glutathione reductase (GR) and glutathione peroxidase (GPx) in RBCs and plasma. Depending of the biomarker considered, 30–50% of EHS self-reporting patients presented statistically significantly increased TBARs, MDA, GSSG and NTT mean plasmatic level values in comparison with normal values obtained in healthy controls (P<0.0001). By contrast, there were no plasmatic level values above the upper normal limits for GSH, GSH/GSSG ratio, total glutathione (GluT) and GSH/GluT ratio, and values for these GSH-associated biomarkers were statistically significantly decreased in 20–40% of the patients (P<0.0001). Furthermore, in RBCs, mean SOD1 and GPx activities were observed to be statistically significantly increased in ~60% and 19% (P<0.0001) of the patients, respectively, while increased GR activity in RBCs was observed in only 6% of the patients. The present study reports for the first time, to the best of our knowledge, that overall ~80% of EHS self-reporting patients present with one, two or three detectable oxidative stress biomarkers in their peripheral blood, meaning that these patients-as is the case for cancer, Alzheimer's disease or other pathological conditions-present with a true objective new pathological disorder.