Tissue Oxidative Stress Parameters Research Articles

Thirty-day experimental diabetes impairs contractility and increases fatigue resistance in rat diaphragm muscle associated with increased anti-oxidative activity.

Diabetes mellitus is a metabolic disorder that can generate tissue damage through several pathways. Alteration and dysfunction of skeletal muscle are reported including respiratory muscles, which may compromise respiratory parameters in diabetic patients. We have aimed to evaluate the diaphragm muscle contractility, tissue remodeling, oxidative stress, and inflammatory parameters from 30 day streptozotocin-treated rats. The diaphragm contractility was assessed using isolated muscle, tissue remodeling using histology and zymography techniques, and tissue oxidative stress and inflammatory parameters by enzyme activity assay. Our data revealed in the diabetes mellitus group an increase in maximum tetanic force (4.82 ± 0.13 versus 4.24 ± 0.18 N/cm2 (p = 0.015)) and fatigue resistance (139.16 ± 10.78 versus 62.25 ± 4.45 s (p < 0.001)), reduction of 35.4% in muscle trophism (p < 0.001), increase of 32.6% of collagen deposition (p = 0.007), reduction of 21.3% in N-acetylglucosaminidase activity (p < 0.001), and increase of 246.7% of catalase activity (p = 0.002) without changes in reactive oxygen species (p = 0.518) and tissue lipid peroxidation (p = 0.664). All observed changes are attributed to the poor glycemic control (471.20 ± 16.91 versus 80.00 ± 3.42 mg/dL (p < 0.001)), which caused defective tissue regeneration and increased catalase activity as a compensatory mechanism.

Investigation of Analgesic Minimum Effective Dose of Apelin‐13 With Different Doses of Intraperitoneal Injections and its Effects on Kidney Tissue

Background and AimsApelin and APJ form a signaling pathway and are widely expressed in a variety of tissues including the heart, kidney and vessels. Apelin and APJ have various effects in many systems such as regulation of blood pressure and vascular tone, cardiac contractility, nociception, heart rate, apoptosis, inflammation. Apelin‐13 has a potential analgesic and proanalgesic effect, although the sites of analgesic effects are uncertain and controversial in terms of results. The fact that apelin can be used as a protective and therapeutic agent in the future will make important contributions both for human health and economically. The aim of the study is to investigate the analgesic minimum effective dose of Apelin‐13 with different doses of intraperitoneal application and its effects on kidney tissue.MethodsThirty Wistar Albino male rats were randomly divided into 5 groups. Rats were designated as control, Apelin‐25, Apelin‐50, Apelin‐100 and Apelin‐200 groups. Apelin‐13 was administered intraperitoneally at 25, 50, 100 and 200 μg/kg doses. The same volume of saline was administered intraperitoneally to the control group. Hot plate test was performed to evaluate analgesic efficacy at 0 and 30 minutes, 1 and 2 hours after administration. All rats were euthanized 24 hours after administration by intraperitoneal ketamine 100 mg/kg. Renal tissues were removed without traumatization and sent to the laboratory for evaluation of histological and oxidant status.ResultsIn the hot plate test, application of apelin 50 μg/kg and above had significantly more analgesic effects than the control group. 25 μg/kg apelin application was found to have no analgesic effect. When kidney tissues were examined, at the doses of 200 μg/kg Apelin; vascular vacuolization and hypertrophy, bowman dilatation and tubular cell shedding were significantly increased but not at the control group, 25 and 50 μg/kg Apelin groups (Figure 1– 2). When the oxidative status was evaluated with TAS and TOS, 200 μg/kg Apelin increased the oxidant parameters while reducing the antioxidant parameters. There was no significant change below this dose. It was also correlated with histopathological findings.ConclusionThat seems to be the first study on the analgesic effects of apelin in different doses in the literatüre and 50 μg/kg apelin is the minimum analgesic effective dose. The administration of 200 μg/kg apelin‐13 adversely affected kidney tissue histologically and tissue oxidative stress parameters increase by the high doses. Other aspects of these findings, including clinical significance and practical applications, merit further experimental and clinical investigation.Support or Funding InformationThis study was conducted in the GUDAM Laboratory of Gazi University with the consent of Experimental Animals Ethics Committee of Gazi University with the code G.U.ET‐19.024. The study was supported by Gazi University Scientific Research Committee (Scientific Research Project No. 01/2019‐44).Control group, renal tissue (10X H&amp;E)Figure 1200 μg/kg application of Apelin 13 increased vascular vacuolization and hypertrophy, bowman dilatation and tubular cell shedding (10X H&amp;E)Figure 2

Cardiac Oxidative Stress And Matrix Metalloproteinases Activities In Streptozotocin-Induced Metabolic Syndrome And Diabetes Mellitus In Wistar Male Rats

Background and Aims: The aim of this study was to examine the induction of metabolic syndrome and diabetes mellitus (DM) type I in Wistar male rats using different doses of streptozotocin (STZ), and their influence on the cardiac tissue oxidative stress parameters.

Increased placental expressions of nuclear factor erythroid 2–related factor 2 and antioxidant enzymes in gestational diabetes: Protective mechanisms against the placental oxidative stress?

Objective: Gestational diabetes mellitus is associated with increased oxidative stress. Oxidative stress may contribute to the risk for pregnancy pathologies associated with gestational diabetes mellitus. In this study we investigated the expression of placental nuclear factor erythroid 2–related factor 2 (Nrf2) and antioxidant enzymes of gestational diabetes mellitus and healthy pregnant women and correlated them with the maternal and cord plasma as well as placental tissue oxidative stress parameters.Study design: A cross sectional study was carried out in a South Indian Tamil population. Forty healthy pregnant women and forty gestational diabetes mellitus patients in the gestational age of 32 ± 4weeks were recruited. Maternal plasma, cord plasma and placental oxidative stress parameters were measured. Placental expression of Nrf2, phospho Nrf2, catalase and superoxide dismutase 1(SOD1) were analyzed by western blotting and immunohistochemistry.Results: Placental expression of Nrf2, catalase and SOD1 were found to be significantly higher in gestational diabetes mellitus. The maternal plasma, cord plasma and placental tissue oxidative stress parameters, total antioxidant status (TAS) levels were significantly lower; whereas MDA (malondialdehyde) and MDA/TAS levels were significantly higher in gestational diabetes mellitus. Placental Nrf2 expression correlated positively with the placental catalase expression and negatively with placental TAS levels in both groups.Conclusion: Maternal, fetal and placental oxidative stress was observed in gestational diabetes mellitus. The gestational diabetic placenta had an increased Nrf2 protein expression. The activated placental Nrf2/ antioxidant response element (ARE) pathway might have led to an increased expression of antioxidant enzymes SOD1 and catalase. This may be viewed as a protective mechanism in placenta from the further onslaught of oxidative stress.

Q10 Coenzyme Supplementation can Improve Oxidative Stress Response to Exercise in Metabolic Syndrome in Rats

Background: The metabolic syndrome leads to high morbidity and mortality. Almost all pathological states are associated with oxidative stress (OS) disorders. This study evaluates the effects of Coenzyme Q10 (CoQ10) supplementation on different lifestyles, in relation to serum and tissue OS parameters. Materials and methods: Twelve Wistar rat groups (10 rats/group) were equally divided in three types of diets: standard (St), high fat (HF), high sugar (HS); within each diet group there was one sedentary group with CoQ10 supplementation (100mg/kg body weight), one sedentary without CoQ10, one trained group with CoQ10 and one trained group without CoQ10 supplementation. After 28 days blood samples were collected as follows: after 12 hours of fasting (T0), 1 hour postprandial (T1) and after 1 hour of exercise (T2) or sedentary postprandial time (T3). Thiol groups (SH) and malondialdehyde (MDA) were determined from serum and liver homogenate. Results: Significant changes were observed in fasting MDA for HF (p=0.024 for training, 0.028 for CoQ10). Postprandial, OS status altered, with highest MDA in HF sedentary non-CoQ10 group (3.92±0.37 vs 2.67±0.41nmol/ml in St trained CoQ10). At T2 the untrained and non-CoQ10 groups had the highest MDA levels (up to 22.3% vs T1, p<0.001 in HF) as SH dropped (34.4% decrease vs T1, p<0.001 in HF). At T3 high MDA levels were observed, correlated with low SH (Pearson r=-0.423 overall), irrespective of the CoQ10 supplementation. CoQ10 improved the liver OS status (MDA and SH decreased), but not the exercise, in all diets. Conclusions: CoQ10 supplementation accompanied by chronic exercise improved the OS serum profile, irrespective of the daily diet. CoQ10 lowered liver MDA and SH concentrations.

Pre-treatment with Empagliflozin ameliorates Cisplatin induced acute kidney injury by suppressing apoptosis

Dose-limiting nephrotoxicity restricts Cisplatin use in high therapeutic doses. Empagliflozin showed a reno-protective effect in diabetic nephropathy. We investigated if Empagliflozin can ameliorate Cisplatin nephrotoxicity whether used prophylactically or therapeutically. Forty male Wistar rats were divided into 5 groups: (1) control; (2) Cisplatin-induced nephrotoxicity by single intraperitoneal dose; (3) Empagliflozin was given for 10 days before a single dose of Cisplatin; (4) a single dose of Cisplatin followed by Empagliflozin for 10 days; (5) received Empagliflozin only. Regular assessment of weight was done, biochemical evaluation for serum urea, creatinine, uric acid, albumin, and glucose was performed, kidney tissue nerve growth factor-β (NGF-β) and oxidative stress parameters were measured, kidneys were evaluated histopathologically and immunostained for caspase 3. Cisplatin significantly reduced body weight, NGF-β, and reduced glutathione, elevated urea, creatinine, and malondialdehyde with no effect on other serum biochemical parameters. Histopathologically, there was high acute tubular necrosis (ATN) score with strong immunostaining of caspase 3. The use of Empagliflozin significantly reduced urea and creatinine in both prophylactic and therapeutic, reduced ATN score in the prophylactic group associated with minimal staining of caspase 3 and elevated reduced glutathione. In conclusion, prophylactic Empagliflozin protected against Cisplatin-induced acute kidney injury mainly via anti-apoptotic effect.

Summer savory (Satureja hortensis L.) extract: Phytochemical profile and modulation of cisplatin-induced liver, renal and testicular toxicity

The aim of our study was to examine the potential ameliorating effect of the methanolic extract of Satureja hortensis L. (summer savory) aerial parts against cisplatin-induced oxidative damage in renal, hepatic, and testicular tissues. S. hortensis methanol extract at the doses of 50, 100 and 200 mg/kg of body weight were orally administered to Wistar rats once daily for 10 days. Toxicity was induced by intraperitoneal injection of a single dose of cisplatin (7.5 mg/kg of body weight) on the 5th day of the experiment. Applied treatment with S. hortensis extract restored tissue morphology, ameliorated levels of serum parameters for liver, renal and testes function, tissue oxidative stress parameters, and increased Bcl-2/Bax ratio as an indicator of apoptosis in experimental animals caused by application of cisplatin. UHPLC/DAD/HESI-MS/MS analysis revealed that S. hortensis extract was rich in phenolic compounds with rosmarinic acid (24.9 mg/g) as the main compound, followed by caffeic acid (1.28 mg/g) and naringenin (1.06 mg/g). Our findings suggest that S. hortensis may be a valuable source of dietary and pharmacologically important phenolic compounds, especially rosmarinic acid, in pharmaceutical and functional food formulations in order to maintain normal health conditions or as a remedy in various diseases caused by oxidative damage.

The Protective Effects of Glycyrrhetinic Acid and Chrysin against Ischemia-Reperfusion Injury in Rat Ovaries

Objective To evaluate the protective effects of glycyrrhetinic acid (GA) and chrysin (CH) on experimental ischemia-reperfusion (I/R) injury in rat ovaries using tissue oxidative stress marker levels, hormone levels, and histopathological scores. Methods Sixty healthy rats were randomly divided into six equal groups: control, I/R, I/R + CH (50 mg/kg/day), I/R + GA (100 mg/kg/day), CH (50 mg/kg/day), and GA (100 mg/kg/day). Biochemical, hormonal, and histopathological evaluations were performed on blood and tissue samples 14 days after CH and GA treatment. Results The antioxidant defense system parameters were significantly higher in the ovarian tissues of the I/R + CH and I/R + GA groups than in those of the I/R group. Serum follicle-stimulating hormone levels were significantly reduced, and serum anti-Müllerian hormone levels were significantly increased in rats treated with CH and GA compared with those in the I/R group. Additionally, the histopathological scores of the I/R + CH and I/R + GA groups were significantly improved compared with those of the I/R group. Conclusions The significant improvements in tissue oxidative stress parameters, serum hormone levels, and histological scores observed in this study indicate that treatment with CH or GA may be a conservative approach to prevent I/R injury in adnexal torsion cases after the ovarian detorsion procedure.

Assessment of effect of calcium dobesilate in experimental liver ischemia-reperfusion injury

This study investigates the protective effect of calcium dobesilate (CaDob), an effective antioxidant and anti-inflammatory drug, on experimental liver ischemia-reperfusion injury (IRI). Forty rats were divided into four groups. In Group 1, (sham), only hepatic pedicle was induced. In Group 2 (control), hepatic pedicle was reperfused for 90 min after being clamped for 60 min. No treatment was given in Group 1 and 2. In Group 3 (perioperative CaDob), 100 mg/kg CaDob was given 2 hours prior to the operation in which hepatic pedicle was reperfused for 90 min following a 60-min clamp. In Group 4 (preoperative CaDob), after 100 mg/kg/day CaDob was given for 10 days before the operation, hepatic pedicle was clamped for 60 min and reperfused for 90 minutes. At the end of these procedures, blood and liver tissue samples were collected for biochemical and histopathological assessment. Liver function tests and tissue oxidative stress parameters were significantly lower in the preoperative and perioperative treatment groups than the control group. Furthermore, it was observed that histopathological injury in the control group significantly decreased in both perioperative and preoperative treatment groups. Calcium dobesilate demonstrated a significant hepatoprotective effect in terms of its antioxidant and anti-inflammatory effects.

Effects of Apigenin on Experimental Ischemia/Reperfusion Injury in the Rat Ovary.

Background:Apigenin is a plant-derived compound belonging to the flavone class, which possess antioxidant, free-radical-scavenging and anti-inflammatory properties.Aims:To address the effects of apigenin on serum anti-mullerian hormone levels, tissue oxidative stress parameters and histopathological changes in ovarian ischemia/reperfusion injury.Study Design:Animal experiment.Methods:Twenty-eight female Wistar albino rats were randomly separated into four sections: Sham operation (group 1), ischemia/reperfusion plus saline (group 2), ischemia/reperfusion plus dimethyl sulfoxide (group 3) and ischemia/reperfusion plus apigenin (group 4). In all ischemia/reperfusion groups, a bilateral adnexal 3-h period of ischemia was performed, followed by 3-h of reperfusion. A single dose of 15 mg/kg apigenin was given intraperitoneally 60 min before reperfusion in group 4. After 3-h of reperfusion, both ovaries were removed, and blood samples were collected. The main outcome measures were serum anti-mullerian hormone levels, ovarian tissue malondialdehyde, total nitric oxide, Cu/Zn superoxide dismutase, catalase and glutathione levels and histopathological damage scores.Results:The ovarian tissue nitric oxide level was significantly lower, and the glutathione level was significantly higher in group 4 compared with groups 2 and 3. There was no significant difference in anti-mullerian hormone levels among the three ischemia/reperfusion groups. The histopathological damage score was lower in group 4 than in groups 2 and 3 (p>0.05).Conclusion:Administration of apigenin has no significant protective effect on ovarian reserve and tissue damage in ovarian ischemia/reperfusion injury.

Protective effects of Balanites aegyptiaca extract, Melatonin and Ursodeoxycholic acid against hepatotoxicity induced by Methotrexate in male rats.

To compare the degree of ameliorative effects of Melatonin (MEL), Ursodeoxycholic acid (UDCA) and Balanites aegyptiaca (BA) against hepatotoxicity induced by MTX for one month. Eighty adult male rats (Sprague Dawely) weighing (190±10g), were randomly divided into eight equal groups: Control, MTX, MEL, BA, UDCA, MTX+MEL, MTX+BA, MTX+UDCA. Liver function biomarker enzymes, liver tissue oxidative stress parameters, together with total antioxidant capacity and tumor necrosis factor (TNF-α) were determined. Histopathological and immunohistochemistry examinations for TNF-α were also done. MTX showed significant increase in alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), total and direct bilirubin, as well as TNF-α levels, oxidized glutathione (GSSG), malodialdehyde (MDA) and nitric oxide (NO). Whereas total protein, albumin, total antioxidant capacity, reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) levels were significantly decreased in MTX treated group. These alterations were improved by MEL and BA treatment, whereas no improvement was noticed in UDCA treatment. BA may be as promising as MEL in the hepatoprotection against MTX toxicity through their antioxidant and radical scavenging activities. In addition, it is not recommended to co-administer UDCA with MTX as it enhanced inflammation and damage to the liver.

Effect of Chlorpyrifos and Lead Acetate on Lipid Peroxidation and Antioxidant Enzyme Activity in Different Rat Tissues: The Possible Protective Role of Vitamin C

The present study was designed to evaluate the effects of chlorpyrifos, lead acetate, vitamin C alone, and in combination on tissue oxidative stress parameters in wistar rats. Rats of 150-200g body weight were divided into eight groups of six animals each and subjected to various daily oral treatment regimes for 98 days. Group I served as control receiving only corn oil, group II received chlorpyrifos @ 5.5 mg/ kg in corn oil, group III received lead acetate @100 ppm in water, whereas animals in group IV received a combination of chlorpyrifos @ 5.5mg/kg in corn oil and lead acetate @ 100 ppm in water. Group V received vitamin C @ 100mg/kg in water, group VIth received a combination of chlorpyrifos @ 5.5mg/kg and vitamin C @ 100mg/kg, group VIIth received lead acetate @ 100 ppm in water and vitamin C @ 100mg/kg and group VIII received chlorpyrifos @ 5.5mg/kg, lead acetate @100ppm in water and vitamin C @ 100mg/kg. A significant increase in the levels of thiobarbituric acid reactive substances (TBARS) was observed in various tissues of both chlorpyrifos and lead treated rats. While as the levels of catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione-s-transferase(GST) showed a significant decrease in these tissues. However, chlorpyrifos and lead acetate, exposure to rats fed with antioxidant vitamin C prevented derangement of these antioxidant parameters. It is recommended that further research be geared towards identifying more agents that may ameliorate such adverse effects.

Poly-ADP-ribose polymerase inhibition provides protection against lung injury in a rat paraquat toxicity model.

Paraquat (PQ) is a widely used herbicide. Exposure to PQ at toxic doses can result in fatal acute lung injury. Inhibition of the poly-(ADP-ribose) polymerase (PARP) enzyme alleviates inflammation and necrosis in various pathologies. Here we aimed to evaluate the effects of PARP inhibition on PQ-induced lung damage in a rat experimental model. Female Sprague-Dawley rats (n=24) were allocated into three groups: sham, PQ and PQ+3-aminobenzamide (3-AB) that is a PARP inhibitor, groups. Experimental lung injury was induced by administration of 15mg/kg PQ intraperitoneally in PQ and PQ+3-AB groups. 3-AB (10mg/kg twice per day) was administered to the PQ+3-AB group for four consecutive days. The animals were killed on the fifth day following PQ administration. Lung tissue and blood samples were collected and stored until analysis. Serum lactate dehydrogenase (LDH) and neopterin levels, tissue oxidative stress parameters, transforming growth factor-beta1 (TGF-β) levels and histological injury scores in the PQ+3-AB group were significantly lower than in the PQ group (P<0.05, PQ vs. PQ+3-AB). Total antioxidant capacity in the PQ+3-AB group was significantly higher than in the PQ group (P<0.05, PQ+3-AB vs. PQ). Our results suggested that the use of PARP inhibitors following PQ toxicity might be useful for minimizing lung injury due to paraquat toxicity.

Medical ozone therapy reduces shock wave therapy-induced renal injury

Objectives: Extracorporeal shock wave (ESW) lithotripsy is the preferred treatment modality for uncomplicated kidney stones. More recently free oxygen radical production following ESW application has been considered to be crucial in shock wave-induced renal damage. It has been shown that ozone therapy (OT) has ameliorative and preventive effects against various pathological conditions due to increased nitro-oxidative stress. In current study, we aimed to evaluate the efficacy of OT against ESW-induced renal injury. Methods: Twenty-four male Sprague–Dawley rats were divided into three groups: sham-operated, ESW, and ESW + OT groups. All groups except sham-operated group were subjected to ESW procedure. ESW + OT group received 1 mg/kg/day of oxygen/ozone mixture intraperitoneally at 2 h before ESW, and OT was continued once a day for consecutive three days. The animals were killed at the 4th day, and kidney tissue and blood samples were harvested for biochemical and histopathologic analysis. Results: Serum ALT and AST levels, serum neopterin, tissue nitrite/nitrate levels, and tissue oxidative stress parameters were increased in the ESW group and almost came close to control values in the treatment group (p < 0.05, ESW vs. ESW + OT). Histopathological injury scores were significantly lower in treatment group than the ESW group (p < 0.05, ESW vs. ESW + OT). Immunohistochemical iNOS staining scores in ESW group were higher than those of sham-operated group (p < 0.05, ESW vs. sham-operated), iNOS staining scores in OT group were significantly lower than the ESW group (p < 0.05, ESW + OT vs. ESW). Conclusion: OT ameliorates nitro-oxidative stress and reduces the severity of pathological changes in the experimental ESW-induced renal injury of rat model.

The relationship between epicardial adipose tissue thickness and oxidative stress parameters in patients with isolated polycystic ovary syndrome

Purpose: The aim of this study is to evaluate the correlation between epicardial adipose tissue thickness and oxidative stress parameters in patients with polycystic ovarian syndrome.Methods: The study included 35 patients with PCOS and 35 healthy women. Transthoracic echocardiography was used to measure the epicardial adipose tissue thickness (EATT) of all patients. For all patients, serum TOS, TAS, hs-CRP, and insulin levels were measured according to the literature, and the HOMA-IR values were calculated. Independent samples t-test, Pearson’s correlation analysis, multivariate logistic regression analysis, and receiver operator characteristic curve (ROC) analysis were used in the statistical analysis.Results: Between the patient group and the control group, EATT was significantly higher in the PCOS group compared to the control group (5.4 ± 1.4 mm and 3.9 ± 1.6 mm, respectively; p < 0.001). Similarly, TOS, TAS, and hs-CRP levels were significantly higher in the PCOS group compared to the control group (p < 0.01 for all). The correlation analysis showed a significant positive correlation between EATT and TAS and hs-CRP (r = 0.349, p < 0.01 and r = 0.352, p < 0.01, respectively). Multivariate regression analysis showed a significant correlation between PCOS and EATT, TAS, and diastolic blood pressure (p < 0.05 for all).Conclusions: Epicardial adipose tissue may play a major role in PCOS pathogenesis by leading to an increase in oxidative stress.

Irbesartan, an angiotensin II receptor antagonist, with selective PPAR-gamma-modulating activity improves function and structure of chemotherapy-damaged ovaries in rats.

Cyclophosphamide (CYP) is a chemotherapeutic agent with a potent ovarian toxic effect. CYP induces granulosa cell apoptosis and oxidative stress. Irbesartan (IRB) is a unique ARB with a peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonistic activity. As PPAR-ɣ activation exerts anti-inflammatory effects and reduces ROS production, IRB may further reduce inflammatory chemokine expression and suppress apoptotic cell death. Therefore, this study aimed to evaluate the effects of IRB on the development of CYP-induced ovarian damage. Rats were divided into four groups: control group, IRB group (100 mg/kg, orally), CYP group (100 mg/kg, i.p. single injection), and IRB+CYP group (IRB administered 9 days before and 6 days after CYP administration). Rats sacrificed on day 16 of experiment; estradiol (E2), FSH, and TNF-α levels were estimated in serum. Reduced glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD) and caspase-3 activities, myeloperoxidase (MPO), and IL-10 levels were determined in ovarian tissues. Protein expressions of p53, caspase-3, Ki-67, and Rad-51 were estimated by immunohistochemical and Western blot techniques. CYP produced ovarian damage as indicated from the decline in serum E2; elevation in FSH; unbalance in tissue oxidative stress parameters; increase in MPO, TNF-α levels, caspase-3 activity/expression, p53, and Rad-51 expression; and decrease in IL-10 contents, without effect on Ki-67. On the other hand, IRB, significantly reduced the toxic effects of CYP as indicted from normalization of E2, FSH, oxidative stress, apoptotic, and inflammatory mediators. These data were further supported by histopathological studies. Thus, co-administration of IRB may be promising in alleviating the ovarian toxic effects of CYP.

Anti-hypernociceptive and anti-oxidative effects of locally treated dobutamine in diabetic rats.

Oxidative stress as a significant factor in the development of diabetes induced neuropathic pain as well as the potential for prevention of this complication. Therefore, we hypothesized that locally administrated dobutamine, a beta-adrenoreceptor agonist, or esmolol, a beta-adrenoreceptor antagonist, can modulate the oxidative stress and ameliorate the diabetes induced neuropathic pain. Effects of locally (intraplantar) treated two pharmaceutical preparations used in clinical applications, dobutamine or esmolol, were investigated by measuring thermal latencies, mechanical thresholds and several oxidative stress parameters in streptozotocin (STZ) induced diabetic rats. Diabetes induced hyperalgesia and allodynia more effectively relieved by dobutamine than esmolol. Anti-hypersensitive action of dobutamine continued through the experiment. Diabetes induced oxidative damage in the paw tissues since STZ rats showed significant increased malondialdehyde (MDA), nitric oxide (NO) and decreased superoxide dismutase (SOD), catalase (CAT), myeloperoxidase (MPO) in the paw. Dobutamine, but not esmolol, restored the tissue oxidative and nitrossive stress parameters to those observed in the non-diabetic rats. Findings suggest that diabetes-induced oxidative stress may be partially responsible for the development of diabetic neural complications. Amelioration of oxidative stress by locally treated dobutamine can be beneficial in diabetes induced neuropathic pain.

A new combination therapy in severe acute pancreatitis--hyperbaric oxygen plus 3-aminobenzamide: an experimental study.

ObjectivesThis study was designed to evaluate effects of hyperbaric oxygen (HBO) plus 3-aminobenzamide (3-AB) cotreatment on tissue oxidative stress parameters (TOSp), tissue histopathology scores (THSc), and bacterial translocations (Bact-Trans) in an experimental model of severe acute pancreatitis (AP).MethodsSeventy-five Sprague-Dawley rats were randomized into 5 groups. Group 1 received sham. Severe AP was induced by intraductal taurocholate infusion and then group 2 received saline, group 3 received 3-AB, group 4 received 3-AB plus HBO, and group 5 received HBO. 3-Aminobenzamide (10 mg/kg per day, once daily, intraperitoneal) and saline (1 mL/kg) were started right after the induction, whereas HBO (2,8 atm pressure, BID, 90 minutes each) was started at the sixth hour. The rats were euthanized at the 54th hour, and TOSp, THSc, and Bact-Trans were studied.ResultsIn treatment groups 3 and 5, Bact-Trans (P < 0.05, P < 0.05), TOSp (P < 0.05, P < 0.05), and THSc (P < 0.001, P < 0.001) were significantly lower than controls. In addition to these findings, group 4 (cotreatment) showed the most significant effect on Bact-Trans and THSc (P < 0.001, P < 0.001) and also better in TOSp (P < 0.02).ConclusionsPoly(ADP-ribose) polymerase inhibition by 3-AB and HBO treatment alone was effective in the course of severe AP, and favorable with cotreatment because of the improved cascades of inflammatory process by different aspects.

Anti-inflammatory and Antioxidative Activities of Safranal in the Reduction of Renal Dysfunction and Damage that Occur in Diabetic Nephropathy.

Diabetic nephropathy is one of the most important complications of both type 1 and type 2 diabetes. The aim of this study is to investigate the curative and renal damage-reducing effects of safranal on inflammation and oxidative stress in diabetic nephropathy. Experimental type 2 diabetes was created in rats by use of high-fat diet (HFD) and streptozotocin (STZ) in the experimental animals. Safranal was then administered to two of the five experimental groups (type 2 diabetes group (DYB) and HFD groups) for a period of 4 weeks. At the end of the 10-week study, the serum blood urea nitrogen (BUN) and creatinine (CREA) levels, renal tissue oxidative stress parameters (total antioxidant capacity (TAS), total oxidant capacity (TOS), oxidative stress index (OSI), GSH, NO), and cytokine levels (TNF-α, IL-1β, IL-18, IFN-γ) were analyzed. In addition, the effect of safranal on the diabetic nephropathy-induced damage in renal tissue was also analyzed histopathologically. In this study, safranal was found to reduce dysfunction (lowered BUN and CREA levels) and tissue damage (histopathological data) that occur in renal tissue, by means of its both antioxidative and anti-inflammatory activities. In the light of these results, we suggest that safranal contributes to the development of new treatment protocols in the treatment of type 2 diabetes and its complication diabetic nephropathy.

Ultrastructural view of a promising anti TNF-α agent on hepatic ischaemia reperfusion injury.

Ischemia reperfusion causes injury to the liver cells during transplantation, trauma and emergency surgery. We investigated whether the anti TNF-α agent, etanercept, can reduce injury in an animal model of ischemia reperfusion owing to the fact that TNF-α plays a critical role in the process of inflammation. Thirty rats were divided into three groups: sham (Group 1), control (Group 2), etanercept (5 mg/kg) treatment (Group 3). Ischemia-reperfusion model was carried out by clamping the hepatic pedicle for 45 min and then reperfusing the liver for 60 min. Etanercept (5 mg/kg) was injected intraperitoneally 5 min prior to reperfusion. At the end of the procedures, blood and liver tissue samples were obtained for biochemical and histopathological assessment. Control and treatment groups showed significant differences in hepatic function tests, plasma and tissue oxidative stress parameters. Samples in the control group histopathologically showed morphologic abnormalities specific to ischemia reperfusion. Histomorphologic findings in the treatment groups showed similar features as the sham group. Our evidence suggests that TNF-α plays a key role in liver ischemia reperfusion injury and etanercept may provide a novel therapeutic approach for patients undergoing liver surgical procedure (Tab. 3, Fig. 4, Ref. 22).