Improvement In Oxidative Stress Parameters Research Articles

Prospective affirmative therapeutics of cannabidiol oil mitigates doxorubicin-induced abnormalities in kidney function, inflammation, and renal tissue changes

Nephropathy is the decline in kidney function. A promising treatment for numerous types of illness is using natural materials as natural chemical compounds. The inquiry was conducted to investigate cannabidiol (CBD) potential for renal syndrome protection. The five equal groups of fifty male Sprague-Dawley rats weighing 150 ± 25 g each were designed; group I received distilled water orally, while group II got an intraperitoneal injection of doxorubicin (18 mg/kg bwt). Group III received CBD (26 mg/kg bwt) orally, while group IV received 1 ml of CBD (26 mg/kg bwt) and group V received trimetazidine (10 mg/kg bwt), in addition to a single intraperitoneal dose of doxorubicin (18 mg/kg bwt) on the 11th day for both groups (IV, V). The administration of CBD (26 mg/kg bwt) led to a noticeable improvement in oxidative stress parameters (SOD and GSH) in rats by significantly lowering enzyme activity (ALT and AST), as well as serum creatinine and urea, IL-6, and MDA, confirming the anti-inflammatory accuracy of CBD linked to significant lowering to IL6R DNA frequency concentration in line with histopathology results. As a result of its anti-inflammatory and antioxidant capabilities, cannabidiol may have protective quality, and CBD medication could be related to controlling renal problems.

Preventive effect of quercetin-Loaded nanophytosome against autistic-like damage in maternal separation model: The possible role of Caspase-3, Bax/Bcl-2 and Nrf2

The autism is an abnormality in the neuronal advance which starts before age 3 recognized by defective behaviors. This study aimed to make quercetin-loaded nanophytosomes (QNP) on behavioral deficits, cerebellar oxidative stress and apoptosis in an autistic-like model caused by maternal separation (MS). The newborn rats are randomly categorized into seven groups, including control, positive control, disease, and diseases treated with quercetin (10 and 40 mg/kg) and QNP (10 and 40 mg/kg). Pups exposed to MS for 3 h per day from postnatal days (PND) 1–9 showed behavioral impairment in adult rats compared to control group. The oral administration of quercetin and QNP was constantly started after the lactation period (21 postnatal days) for three weeks. Autistic-like behaviors, antioxidant parameters, and Nrf2, Bax/Bcl-2, and Caspase-3 expressions were surveyed in the cerebellum. Quercetin (40 mg/kg) treated improved some behavioral disorders. Also, the improvement of oxidative stress parameters, Nrf2 and apoptotic factors gene expression was observed in the cerebellum of quercetin (40 mg/kg) treated (p < 0.01). QNP treatment (10 and 40 mg/kg) significantly ameliorated anxiety-like behaviors, line crossing, and grooming index (p < 0.001), lipid peroxidation (p < 0.001), and increased catalase (CAT) (p < 0.001), superoxide dismutase (SOD) (p < 0.001), glutathione peroxidase (GPx) (p < 0.001) activity, and glutathione (GSH) levels (p < 0.05). Moreover, QNP significantly reduced Caspase-3 and Bax expression (p < 0.001), but increased Bcl-2, and Nrf2 expressions (p < 0.001). These findings indicated that QNP due to its high bioavailability was more effective than quercetin can be reduced autistic-like behavior, oxidative and apoptotic damages in the model of MS rats.

Therapeutic potential of probiotics – Lactobacillus plantarum UBLP40 and Bacillus clausii UBBC07 on thioacetamide-induced acute hepatic encephalopathy in rats

Hepatic encephalopathy (HE) or hepatic coma is a demanding, not utterly understood complication of acute and chronic liver dysfunction and portosystemic shunting. In HE, hyperammonemia and inflammatory responses are believed to act in synergism. Probiotics, Lactobacillus plantarum UBLP40 and Bacillus clausii UBBC07 reduce small intestinal bacterial overgrowth and hyperammonemia, thereby preventing HE development. The effect of probiotics-Lactobacillus plantarum UBLP40 (107CFU/day, 14days) and Bacillus clausii UBBC07 (107CFU/day, 14days) combination and standard drug-lactulose (2.5ml/kg in 3 divided doses, 14days) was studied in thioacetamide (250mg/kg for three days) induced acute HE in rats by measuring behavioural parameters, biochemical parameters (serum AST, ALT, ALP and ammonia level), neurochemical parameters and histopathology study in brain and liver. In contrast to only thioacetamide treated rats, probiotics treatment substantially (p < 0.001) reduced liver function parameters, i.e. serum AST, ALT, ALP, and ammonia, improved behaviour parameters, i.e. decreased motor disruption, improved memory impairment. Probiotics treated rats have also shown a substantial improvement in oxidative stress parameters i.e. reduced lipid peroxidation and increased glutathione level in brain tissue and ameliorated the histopathological changes induced by thioacetamide in the brain and liver. It can be concluded based on the findings that the combination therapy of Lactobacillus plantarum UBLP40 and Bacillus clausiiUBBC07 proves to be effective in acute hepatic encephalopathy in the preclinical stage, and further studies are required to assess this therapy potential in the clinical setting.

Investigation of the clinical efficacy of Zn supplementation in improvement of oxidative stress parameters: A systematic review and dose-response meta-analysis of controlled clinical trials.

Clinical efficacy of zinc (Zn) supplementation in the improvement of oxidative stress biomarkers has been investigated in some clinical trial studies. The purpose of the current dose-response meta-analysis is to systematically aggregate and evaluate all related studies to highlight the possible effect of Zn supplementation on oxidative stress. Systematic search was performed on Scopus, PubMed/Medline, Web of Science and Embase up to 31 December 2020. The random effect method was used to perform pooled analysis. Possible sources of heterogeneity were found using subgroup analysis and meta-regression. In the presence of publication bias, trim and fill analysis was performed to adjust the results. Non-linear relationship between effect size and variables was investigated by performing dose-response analysis. The quality of included studies was assessed using Cochrane Collaboration's tool. Pooled-analysis of 18 studies showed that Zn supplementation improved MDA and Hcys levels (SMD=-1.53μmol/L; 95% CI: -2.22, -0.85; P<.001 and SMD=-0.62μmol/L; 95% CI: -1.08, -0.15; P<.001, respectively). There was no significant effect of Zn supplementation on TBARS (SMD=-0.59μmol/l; 95% CI: -1.31, 0.13; P=.108). Zn had maximum reducing effect on MDA in <40mg/day dosage. Zn supplementation reduces MDA and Hcys levels, but not TBARS level. Supplementation with Zn <40mg/day has an optimum effect on MDA level. Zn supplementation could be considered clinically as a beneficial approach in amending oxidative stress.

Amelioration of Oxidative Stress Through Supplementation of Self- formulated Anti-oxidant Mixture for Early Recovery and Prophylaxis of Bovine Mastitis in Kashmir Valley

Background: During lactation, mammary epithelial cells exhibit a high metabolic rate and thus produce large amounts of ROS and lipid peroxides in vivo (Jin et al. 2014; Ganguly et al., 2016). A surplus of ROS and the absence of optimal amounts of antioxidants (which neutralize these free radicals or ROS) results in oxidative stress (Lykkesfeldt and Svendsen, 2007). A clinical study was undertaken on Bovine Mastitis in Kashmir valley to study the relation between oxidative stress and clinical mastitis. An attempt was also made to see the effect of supplementation of self-formulated anti-oxidant trace mineral mixture on recovery and prophylaxis of Bovine mastitis through amelioration of oxidative stress.Methods: The oxidative stress was assessed through estimation of superoxide dismutase (SOD), catalase, reduced glutathione (GSH), malondialdehyde (MDA) and nitric oxide (NO). In addition, blood trace mineral status for copper (Cu), zinc (Zn), manganese (Mn) and selenium (Se) were also assessed in mastitic animals and compared with normal healthy lactating animals. The utility of anti-oxidants in clinical management of mastitis was measured through response to treatment with trace minerals like Cu, Zn, Mn and Se in addition to conventional antibiotic therapy. Two groups of mastitic animals received two therapeutic regimens. Group I animals received antibiotics and self formulated anti-oxidant mixture at therapeutic doses while as Group II animals received only antibiotics (at same dose rate and frequency). Clinical recovery was assessed on the basis of CMT point score, milk somatic cell count and milk biochemistry. For prophylactic study, forty recently parturated lactating animals having susceptibility to occurrence of mastitis were divided into two groups of twenty animals each. One group of animals was supplemented with self-formulated anti-oxidant mixture at prophylactic doses for a period of thirty days so as to see the effect of supplementation on oxidative stress parameters and occurrence of clinical mastitis.Result: A significant decrease was found in the values of SOD, catalase, GSH and Cu, Zn, Mn and Se but a significant increase was found in the values of MDA and NO in clinical cases of mastitis as compared to healthy control group. Therapeutic regimen I proved efficacious than the therapeutic regimen II in treatment of clinical mastitis with higher recovery rates and lesser number of mean days required for recovery in group I than group II animals. The efficacy of prophylactic treatment was monitored by occurrence of mastitis during the course of therapy and one month after therapy. Group I animals did not suffer from clinical mastitis and showed considerable improvement in oxidative stress parameters, milk SCC and blood trace mineral status as compared to group II.

Effect of melatonin supplementation on oxidative stress parameters: A systematic review and meta-analysis

BackgroundOxidative stress, defined as an imbalance between pro-oxidants and neutralizing antioxidants within the body, is a growing public health concern. Oxidative stress is involved in the progression of nearly all chronic diseases. Melatonin has been suggested to reduce oxidative stress by its potential radical scavenging properties. ObjectiveTo determine the efficacy and safety of melatonin as a therapy for the improvement of oxidative stress parameters in randomized controlled trials. MethodsA systematic database search using Scopus, PubMed/Medline, EMBASE, Web of Science, the Cochrane Controlled Register of Trials and clinicaltrials.gov (https://clinicaltrials.gov) for studies published up to July 2020 was conducted. We included studies which investigated the effect of supplemental melatonin compared to placebo on oxidative stress parameters in unhealthy patients. Quantitative data synthesis was conducted using a random-effects model with standard mean difference (SMD) and 95 % confidence intervals (CI). Cochrane’s Q and I2 values were used to evaluate heterogeneity. ResultsA total of 12 randomized controlled trials (RCTs) were eligible. The meta-analysis indicated an association between melatonin intake and a significant increase in total antioxidant capacity (TAC) (SMD: 0.76; 95 % CI: 0.30, 1.21; I2 = 80.1 %), glutathione (GSH) levels (SMD: 0.57; 95 % CI: 0.32, 0.83; I2 = 15.1 %), superoxide dismutase (SOD) (SMD: 1.38; 95 % CI: 0.13, 2.62; I2 = 86.9 %), glutathione peroxidase (GPx) (SMD: 1.36; 95 % CI: 0.46, 2.30; I2 = 89.3 %), glutathione reductase (GR) (SMD: 1.21; 95 % CI: 0.65, 1.77; I2 = 00.0 %) activities, and a significant reduction in malondialdehyde (MDA) levels (SMD: -0.79; 95 % CI: -1.19, -0.39; I2 = 73.1 %). Melatonin intake was not shown to significantly affect nitric oxide (NO) levels (SMD: -0.24; 95 % CI: -0.61, 0.14; I2 = 00.0 %) or catalase (CAT) activity (SMD: -1.38; 95 % CI: -1.42, 4.18; I2 = 96.6 %). ConclusionMelatonin intake was shown to have a significant impact on improving Oxidative stress parameters. However, future research through large, well-designed randomized controlled trials are required to determine the effect of melatonin on oxidative stress parameters in different age groups and different disease types.

The Effect of Nano-Epigallocatechin-Gallate on Oxidative Stress and Matrix Metalloproteinases in Experimental Diabetes Mellitus.

Background: The antioxidant properties of epigallocatechin-gallate (EGCG), a green tea compound, have been already studied in various diseases. Improving the bioavailability of EGCG by nanoformulation may contribute to a more effective treatment of diabetes mellitus (DM) metabolic consequences and vascular complications. The aim of this study was to test the comparative effect of liposomal EGCG with EGCG solution in experimental DM induced by streptozotocin (STZ) in rats. Method: 28 Wistar-Bratislava rats were randomly divided into four groups (7 animals/group): group 1—control group, with intraperitoneal (i.p.) administration of 1 mL saline solution (C); group 2—STZ administration by i.p. route (60 mg/100 g body weight, bw) (STZ); group 3—STZ administration as before + i.p. administration of EGCG solution (EGCG), 2.5 mg/100 g b.w. as pretreatment; group 4—STZ administration as before + i.p. administration of liposomal EGCG, 2.5 mg/100 g b.w. (L-EGCG). The comparative effects of EGCG and L-EGCG were studied on: (i) oxidative stress parameters such as malondialdehyde (MDA), indirect nitric oxide (NOx) synthesis, and total oxidative status (TOS); (ii) antioxidant status assessed by total antioxidant capacity of plasma (TAC), thiols, and catalase; (iii) matrix-metalloproteinase-2 (MMP-2) and -9 (MMP-9). Results: L-EGCG has a better efficiency regarding the improvement of oxidative stress parameters (highly statistically significant with p-values < 0.001 for MDA, NOx, and TOS) and for antioxidant capacity of plasma (highly significant p < 0.001 for thiols and significant for catalase and TAC with p < 0.05). MMP-2 and -9 were also significantly reduced in the L-EGCG-treated group compared with the EGCG group (p < 0.001). Conclusions: the liposomal nanoformulation of EGCG may serve as an adjuvant therapy in DM due to its unique modulatory effect on oxidative stress/antioxidant biomarkers and MMP-2 and -9.

The Antioxidant Effects of Hydroxytyrosol and Vitamin E on Pediatric Nonalcoholic Fatty Liver Disease, in a Clinical Trial: A New Treatment?

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children. Several studies suggest that the improvement of oxidative stress is suggested as a possible therapeutic strategy for pediatric nonalcoholic steatohepatitis. We performed a randomized, double-blind placebo-controlled trial to test the potential efficacy, assessed by improvement of oxidative stress parameters and liver ultrasound, and tolerability of a mixture of vitamin E and hydroxytyrosol (HXT) in adolescents with biopsy-proven NAFLD. Four hundred forty consecutive patients were screened, 80 of these with biopsy-proven NAFLD were enrolled. Forty patients received an oral dose of HXT and vitamin E and 40 children received the capsules of placebo for 4 months. Seventy patients completed the study. Patients in the treatment arm showed a decrease of insulin resistance (IR), triglyceride levels, oxidative stress parameters, and steatosis grade. Noteworthy, the steatosis improvement correlates with the levels of advanced glycation end products and carbonylated proteins. The HXT and vitamin E treatment improved the main oxidative stress parameters, IR, and steatosis in children with NAFLD. The use of two natural molecules that may have antioxidant effects seems a promising strategy that could be easily diet integrated to improve NAFLD-related liver damage in children.

Oxidative stress/PERK/apoptotic pathways interaction contribute to tramadol neurotoxicity in rat cerebral and cerebellar cortex and thyme enhances the antioxidant defense system: histological, immunohistochemical and ultrastructural study

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Tramadol is an opioid analgesic with several adverse reactions. Oxidative and endoplasmic reticulum (ER) stresses have been involved in the molecular mechanisms underlying tramadol neurotoxicity. Importantly, protein kinase RNA-like ER kinase (PERK) is a key ER-downstream pathway that mediates apoptosis. We aimed to determine the cellular stresses interaction that mediates PERK-induced apoptosis in tramadol-treated rats and to assess the effect of thyme in enhancing the antioxidant defense system in the face of such stresses.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; Forty male Sprague Dawley rats were randomized into 4 groups. Control group, thyme group received thyme extract (500 mg/kg/day) orally. Tramadol group received tramadol HCL (40 mg/Kg/day) dissolved in saline orally. Tramadol + Thyme group received tramadol and thyme extract. After 30 days, frontal motor and cerebellar cortex specimens were biochemically assessed for oxidative stress biomarkers and evaluated for histological, ultrastructural and immunohistochemical changes. &lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; Tramadol group showed a significant elevation in malondialdehyde level with a reduction in superoxide dismutase and catalase enzyme activities. Histologically and ultrastructurally, there were remarkable degenerative and apoptotic changes in the neurons and glial cells. In parallel, we detected a significant increase in integrated density for PERK immunostaining and number of caspase-3 positive cells/HPF compared to control. Tramadol + Thyme group showed improvement in oxidative stress parameters, histological and ultrastructural changes. Moreover, integrated density for PERK immunostaining and number of caspase-3 positive cells/HPF were significantly lower than Tramadol group.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Oxidative and ER stress-mediated PERK/apoptosis axis corroborates to the tramadol-induced neurotoxicity. Therapeutic strategies enhancing antioxidant activity and/or blocking ROS-mediated ER stress pathway may resolve tramadol neurotoxicity.&lt;/p&gt;

Nitric oxide synthase inhibitors protect against brain and liver damage caused by acute malathion intoxication.

To investigate the effect of NG-nitro-l-arginine methyl ester (l-NAME), a non-selective nitric oxide synthase (NOS) inhibitor, and 7-nitroindazole (7-NI), a selective neuronal NOS inhibitor, on oxidative stress and tissue damage in brain and liver and on DNA damage of peripheral blood lymphocytes in malathion intoxicated rats. Malathion (150mg/kg) was given intraperitoneally (i.p.) along with l-NAME or 7-NI (10 or 20mg/kg, i.p.) and rats were euthanized 4h later. The lipid peroxidation product malondialdehyde (MDA), nitric oxide (nitrite), reduced glutathione (GSH) concentrations and paraoxonase-1 (PON-1) activity were measured in both brain and liver. Moreover, the activities of glutathione peroxidase (GPx) acetylcholinesterase (AChE), and butyrylcholinesterase (BChE), total antioxidant capacity (TAC), glucose concentrations were determined in brain. Liver enzyme determination, Comet assay, histopathological examination of brain and liver sections and inducible nitric oxide synthase (iNOS) immunohistochemistry were also performed. (i) Rats treated with only malathion exhibited increased nitric oxide and lipid peroxidation (malondialdehyde) accompanied with a decrease in GSH content, and PON-1 activity in brain and liver. Glutathione peroxidase activity, TAC, glucose concentrations, AChE and BChE activities were decreased in brain. There were also raised liver aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and increased DNA damage of peripheral blood lymphocytes (Comet assay). Malathion caused marked histopathological changes and increased the expression of iNOS in brain and liver tissues. (ii) In brain of malathion-intoxicated rats, l-NAME or 7-NI resulted in decreased nitrite and MDA contents while increasing TAC and PON1 activity. Reduced GSH and GPx activity showed an increase by l-NAME. AChE activity increased by 20mg/kg l-NAME and 10mg/kg 7-NI. AChE activity decreased by the higher dose of 7-NI while either dose of 7-NI resulted in decreased BChE activity. (iii) In liver of malathion-intoxicated rats, decreased MDA content was observed after l-NAME or 7-NI. Nitrite level was unchanged by l-NAME but increased after 7-NI which also resulted in decreased GSH concentration and PON1 activity. Either inhibitor resulted in decreased liver ALT activity. (iv) DNA damage of peripheral blood lymphocytes was markedly inhibited by l-NAME or 7-NI treatment. (v) iNOS expression in brain and liver decreased by l-NAME or 7-NI. (vi) More marked improvement of the histopathological alterations induced by malathion in brain and liver was observed after 7-NI compared with l-NAME. In malathion intoxicated rats, the neuronal NOS inhibitor 7-NI and to much less extent l-NAME were able to protect the brain and liver tissue integrity along with improvement in oxidative stress parameters. The decrease in DNA damage of peripheral blood lymphocytes by NOS inhibitors also suggests the involvement of nitric oxide in this process.

A study of diaphyseal nutrient foramina in human tibia

To investigate the effect of NG-nitro-l-arginine methyl ester (l-NAME), a non-selective nitric oxide synthase (NOS) inhibitor, and 7-nitroindazole (7-NI), a selective neuronal NOS inhibitor, on oxidative stress and tissue damage in brain and liver and on DNA damage of peripheral blood lymphocytes in malathion intoxicated rats.Malathion (150 mg/kg) was given intraperitoneally (i.p.) along with l-NAME or 7-NI (10 or 20 mg/kg, i.p.) and rats were euthanized 4 h later. The lipid peroxidation product malondialdehyde (MDA), nitric oxide (nitrite), reduced glutathione (GSH) concentrations and paraoxonase-1 (PON-1) activity were measured in both brain and liver. Moreover, the activities of glutathione peroxidase (GPx) acetylcholinesterase (AChE), and butyrylcholinesterase (BChE), total antioxidant capacity (TAC), glucose concentrations were determined in brain. Liver enzyme determination, Comet assay, histopathological examination of brain and liver sections and inducible nitric oxide synthase (iNOS) immunohistochemistry were also performed.(i) Rats treated with only malathion exhibited increased nitric oxide and lipid peroxidation (malondialdehyde) accompanied with a decrease in GSH content, and PON-1 activity in brain and liver. Glutathione peroxidase activity, TAC, glucose concentrations, AChE and BChE activities were decreased in brain. There were also raised liver aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and increased DNA damage of peripheral blood lymphocytes (Comet assay). Malathion caused marked histopathological changes and increased the expression of iNOS in brain and liver tissues. (ii) In brain of malathion-intoxicated rats, l-NAME or 7-NI resulted in decreased nitrite and MDA contents while increasing TAC and PON1 activity. Reduced GSH and GPx activity showed an increase by l-NAME. AChE activity increased by 20 mg/kg l-NAME and 10 mg/kg 7-NI. AChE activity decreased by the higher dose of 7-NI while either dose of 7-NI resulted in decreased BChE activity. (iii) In liver of malathion-intoxicated rats, decreased MDA content was observed after l-NAME or 7-NI. Nitrite level was unchanged by l-NAME but increased after 7-NI which also resulted in decreased GSH concentration and PON1 activity. Either inhibitor resulted in decreased liver ALT activity. (iv) DNA damage of peripheral blood lymphocytes was markedly inhibited by l-NAME or 7-NI treatment. (v) iNOS expression in brain and liver decreased by l-NAME or 7-NI. (vi) More marked improvement of the histopathological alterations induced by malathion in brain and liver was observed after 7-NI compared with l-NAME.In malathion intoxicated rats, the neuronal NOS inhibitor 7-NI and to much less extent l-NAME were able to protect the brain and liver tissue integrity along with improvement in oxidative stress parameters. The decrease in DNA damage of peripheral blood lymphocytes by NOS inhibitors also suggests the involvement of nitric oxide in this process.

Potential protective effect of etanercept and aminoguanidine in methotrexate-induced hepatotoxicity and nephrotoxicity in rats

Methotrexate (MTX), a chemotherapeutic and immunosuppressant drug, is generally well-tolerated by most patients. However, its cytotoxic nature contributes to life-threatening side effects including hepatotoxicity and nephrotoxicity. The present study investigated the possible role of tumor necrosis factor-alpha (TNF-α) inhibitor, etanercept and inducible nitric oxide synthase (iNOS) inhibitor, aminoguanidine, on MTX-induced hepatotoxicity and nephrotoxicity in rats. Rats were divided into 7 groups: control group, etanercept group, aminoguanidine group, MTX group, MTX+etanercept group, MTX+aminoguanidine group, and MTX+etanercept+aminoguanidine group. MTX caused hepatotoxicity and nephrotoxicity as evidenced biochemically by significant increase in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea and creatinine, respectively as well as by histopathological changes. Such effects were associated with significant changes in oxidative stress markers (malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), catalase, and glutathione (GSH)) as well as by upregulation of TNF-α, iNOS and caspase-3 expressions in hepatic and renal tissues. Etanercept and aminoguanidine significantly attenuated MTX-hepatotoxicity and nephrotoxicity. The protective effect of either agent was associated with significant improvement in oxidative stress parameters as well as by downregulation of TNF-α, iNOS and caspase-3 expressions in hepatic and renal tissues. The study suggested that inhibitors of either TNF-α and/or iNOS have protective effect in MTX-induced hepatotoxicity and nephrotoxicity. The protective effect of either agent relies, at least partially, on their antioxidant effects and decreased TNF-α, iNOS, and caspase-3 expressions.

Treatment of hyperglycaemia in newly diagnosed diabetic patients is associated with a reduction in oxidative stress and improvement in β‐cell function

There exist several reports demonstrating enhancement in oxidative stress in diabetic patients; however, serial and comprehensive measurement of oxidative stress parameters in newly diagnosed diabetic patients is not yet reported. We measured the oxidative stress parameters in diabetic patients serially from the time of diagnosis and after starting treatment to study their association with glycaemia, insulin resistance and β-cell function. Fifty-four newly diagnosed diabetic patients were studied at diagnosis and 4 and 8 weeks after initiating anti-hyperglycaemic treatment. Oxidative stress parameters included activity of antioxidant enzymes, concentration of antioxidant molecules and damage markers. Oxidative stress score was computed as a collective measure of oxidative stress to interpret total oxidative stress state. Association of changing glucose levels with changing oxidative stress parameters over 8 weeks and association of oxidative stress score with insulin resistance and β-cell function was analysed by homeostasis model assessment (HOMA-IR and HOMA-β, respectively). Eight weeks of treatment improved HbA1C from 9.8 ± 2.1 to 7.7 ± 1.0%. There was a significant increase in oxidative stress in diabetic patients [23.8 (95% CI 20.0, 27.6)] compared with non-diabetic subjects [-1.2 (-3.4, 0.9)] (p < 0.001). Non-diabetic subjects showed a stable status over 8 weeks. Improvement in hyperglycaemia in diabetic patients was associated with an improvement in oxidative stress parameters irrespective of the anti-diabetic treatment received. Oxidative stress score fell after 8 weeks and was significantly associated with an improvement in HOMA-β (standardized β = -0.38, p < 0.01) but not with HOMA-IR. Controlling hyperglycaemia in diabetic patients alleviates oxidative stress within 8 weeks of treatment, and improvement in oxidative stress parameters was related to an improved β-cell function.

The Effect of Exopolysaccharide-Producing Probiotic Strains on Gut Oxidative Damage in Experimental Colitis

Oxidative stress plays a role in disease initiation and progression in inflammatory bowel disease (IBD) and manipulation of this pathway may attenuate disease progress. In this study, the effect of exopolysaccharide (EPS)-producing probiotic bacteria on gut oxidative damage was evaluated in a rat model of experimental colitis. Colitis was induced by intracolonic administration of acetic acid. Rats were treated daily with two probiotic strains, L. delbrueckii subsp. bulgaricus B3 strain (EPS of 211 mg/l; high-EPS group) or L. delbrueckii subsp. bulgaricus A13 strain (EPS of 27 mg/l; low-EPS group), which were given directly into the stomach. Non-colitis-fed control and preventative groups were only treated with the high-EPS producing strain. Antioxidant enzyme activities (superoxide dismutase, catalase, total glutathione, reduced glutathione, glutathione disulfide) and lipid peroxidation were measured in colonic tissue samples after a treatment period of 7 days. Significant oxidative damage was associated with a higher level of malondialdehyde (MDA) activity and reduced antioxidant enzyme activities in the colitis model group. All antioxidant enzyme activities were higher in both probiotic-treated groups compared with those of the colitis model group (P < 0.001). Lipid peroxidation was significantly ameliorated in both probiotic groups. The improvement of oxidative stress parameters was significantly more in the high-EPS group than in the low-EPS group (P < 0.001). EPS-producing probiotic bacteria significantly attenuate oxidative stress in experimental colitis. Increased EPS production gives rise to a better probiotic function. These results suggest that EPS molecules could revaluate probiotic strains and exert their beneficial effects on the host and this may have a therapeutic potential.

Oxidative stress parameters after combined fluoxetine and acetylsalicylic acid therapy in depressive patients

There are numerous reports indicating disturbed equilibrium between oxidative processes and antioxidative defense in patients with depression. Moreover, depressive patients are characterized by the presence of elements of an inflammatory process, which is one of the sources of reactive oxygen species (ROS). In view of the above, it was decided to study both the effect of fluoxetine monotherapy and that of fluoxetine co-administered with acetylsalicylic acid on lipid peroxidation and antioxidative defense in patients with the first depressive episode in their life. Seventy seven patients with major depressive disorder (MDD), divided into two groups were included in the study. The first group, consisting of 52 patients, received fluoxetine 20 mg, and the second one, in addition to fluoxetine 20 mg, received 150 mg of acetylsalicylic acid. The activity of antioxidative enzymes, copper-zinc superoxide dismutase (CuZnSOD, SOD1), catalase (CAT), glutathione peroxidase (GPSH-x) and the concentration of malonyldialdehyde (MDA) was determined in erythrocytes, whereas the total antioxidant status (TAS) was determined in the plasma. All parameters were measured before and after three month therapy. The obtained results indicate a significant decrease in the activity of SOD1, CAT and GSHP-x, as well as in MDA concentration after the combined therapy. Also a significant TAS increase was observed after the combined therapy. The study demonstrated that combined therapy with fluoxetine and ASA is characterized by the same efficacy and clinical safety as fluoxetine monotherapy, resulting additionally in improvement of oxidative stress parameters in the patients treated for depression.

Improvement of Oxidative Stress Parameters in MDS Patients with Iron Overload Treated with Deferasirox

Introduction: Using flourescence markers, evidence for oxidative stress has been documented by flow cytometry in red cells (RBC) and other blood cells of patients with congenital and acquired hemolytic anemias (e.g. thalassemia, sickle cell anemia, hereditary spherocytosis and paroxysmal nocturnal hemoglobinuria) as well as in myelodysplatic syndrome (MDS) (Eur. J. Hematol. 79:463,2008). These data included increased generation of reactive oxygen species (ROS) concomittant with a decrease in the cellular content of the major antioxidant reduced gluthatione (GSH), and increased membrane lipid peroxidation. Oxidative stress in these anemias is thought to be mainly due to the accumulation of non-transferrin-bound iron (NTBI) which affects iron homeostasis and results in excess extra-cellular and intra-cellular labile pools: labile plasma iron (LPI) and cellular labile iron pool (LIP) (Cytometry 73:22,2008), respectively, catalyzing ROS generation. The presence of these free iron components is correlated with the severity of hemolysis and the subsequent repetitive blood transfusions, resulting in iron-overload. The purpose of the present study was to measure changes in parameters of iron-overload and oxidative stress in iron-overloaded patients with MDS following treatment with the oral iron-chelator Deferasirox.Patients and Methods: Fifteen patients–5 males and 10 females-(mean age 66 ± 13 years) with “low risk” MDS (IPSS < 1.0) received Deferasirox 20 mg/kg/day (12 patients) or 4–6 mg/kg/day (3 patients) due to side effects mainly gastrointestinal, increased creatinine and rash, for an average period of 95 days (63–163 days). All of them had evidence of iron-overload. Their mean number of transfusions was 65 ± 62, and mean ferritin levels before treatment was 3008 ± 1797 ng/ml. ROS, GSH, lipid peroxidation, LIP and LPI were measured every 3–4 weeks, in RBC, platelets and polymorphonuclear leukocytes (PMN). Blood cell counts, hemoglobin levels and serum ferritin were assayed simulteneously.Results: There was a statistically significant decrease in ROS (28%, p=0.006), lipid peroxidation (138%, p=0.008) and the LIP (23%, p=0.004) of RBC, concomittant with an increase in GSH (123%, p=0.001). GSH was also increased in platelets (48%, p=0.008) and PMN (72%, p=0.001), and LIP decreased in platelets (23%, p=0.004). In 8 patients the mean initial LPI levels of 0.39 units decreased to 0.12 units (p=0.028). There were no significant changes in hemoglobin levels or in any of the other types of blood cells. Mean serum ferritin levels increased in 8 patients by 964 ± 927 ng/ml and decreased in the rest by 1432 ± 1267 ng/ml.Discussion: The results clearly demonstrate that administration of Deferasirox to iron-overloaded MDS patients for a mean period of 3 months resulted in a significant decrease in parameters of oxidative stress mainly in RBC and platelets and in intra-(LIP) and extra-cellular (LPI) species of free iron. Serum ferritin, a major parameter in the assessment of the severity of iron-overload, was increased in 8 patients in the present study, similar to previously reported findings of increased ferritin levels at 12 months following iron chelation with Deferasirox (Am. J. Hematol. 83:611–3, 2008). However, unlike iron stored in ferritin, the major risk of iron-overload is the presence of excess extra and intracellular iron species (LPI and LIP) which are playing an important role in ROS generation and consequent membrane damage in blood cels and in other major organs.. These preliminary data suggest that treatment with Deferasirox, a once-a-day oral iron chelator, reduced the toxic iron species and several parameters of oxidative stress in iron overloaded MDS patients. Furthermore, the novel methodologies applied in this study may be useful for evaluating the severity of the iron-overload and for monitoring the efficacy of iron chelation therapy. Additional studies assessing the correlation of these changes to the long-term morbidity, mortality, and quality of life are definitely warranted in this patient population.

N-ACETYLCYSTEINE TREATMENT IN RAT CHRONIC PANCREATITIS

Aim: N-acetylcysteine (NAC) is essential for the defense against oxidative stress (OS). It was found effective in reducing the disease parameters in acute pancreatitis. However, whether it has a function in alleviation of tissue injury in chronic pancreatitis (CP) is not known. In the present study, we aimed to assess the effect of NAC on fibrosis, atrophy and OS in CP. Materials and Methods: Sixty SD rats were divided into 4 groups (n = 15). Gr I, II and III underwent laparotomy and pancreatic cannulation. Gr I and II received intraductal 2% TNBS to induce CP, and Gr III received 10% ethanol. Gr IV served as controls. By the 4th wk, Gr I was started treatment with i.p NAC (50 mg/kg/d), Gr II and III with i.p. saline for 4 wk, and OS markers, fibrosis and atrophy were examined. Results: Tissue MDA levels decreased (p < 0.001), and SOD and GSH-Px activity increased (p < 0.001 for both) in NAC group. Fibrosis scores in NAC group were lower compared to their controls (p < 0.003), and a significant correlation between the improvement in OS parameters and the decrease in histological score was detected (p < 0.03, p < 0.04 and p < 0.02 for histological score vs. MDA, SOD and GSH-Px, respectively). Conclusions: Administration of NAC decreases the degree of OS in the pancreas in rat CP. Moreover, it has profound beneficial effects on tissue fibrosis and atrophy. NAC treatment may be of clinical benefit in the treatment of patients with CP.