Tissue Oxidative Stress Levels Research Articles

The Interplay between Perioperative Oxidative Stress and Hepatic Dysfunction after Human Liver Resection: A Prospective Observational Pilot Study.

Post-hepatectomy liver failure (PHLF) remains the major contributor to death after liver resection. Oxidative stress is associated with postoperative complications, but its impact on liver function is unclear. This first in-human, prospective, single-center, observational pilot study evaluated perioperative oxidative stress and PHLF according to the ISGLS (International Study Group for Liver Surgery). Serum 8-isoprostane, 4-hydroxynonenal (4-HNE), total antioxidative capacity, vitamins A and E, and intraoperative, sequential hepatic tissue 4-HNE and UCP2 (uncoupling protein 2) immunohistochemistry (IHC) were assessed. The interaction with known risk factors for PHLF and the predictive potential of oxidative stress markers were analyzed. Overall, 52 patients were included (69.2% major liver resection). Thirteen patients (25%) experienced PHLF, a major factor for 90-day mortality (23% vs. 0%; p = 0.013). Post-resection, pro-oxidative 8-isoprostane significantly increased (p = 0.038), while 4-HNE declined immediately (p < 0.001). Antioxidative markers showed patterns of consumption starting post-resection (p < 0.001). Liver tissue oxidative stress increased stepwise from biopsies taken after laparotomy to post-resection in situ liver and resection specimens (all p < 0.001). Cholangiocarcinoma patients demonstrated significantly higher serum and tissue oxidative stress levels at various timepoints, with consistently higher preoperative values in advanced tumor stages. Combining intraoperative, post-resection 4-HNE serum levels and in situ IHC early predicted PHLF with an AUC of 0.855 (63.6% vs. 0%; p < 0.001). This was also associated with grade B/C PHLF (36.4% vs. 0%; p = 0.021) and 90-day mortality (18.2% vs. 0%; p = 0.036). In conclusion, distinct patterns of perioperative oxidative stress levels occur in patients with liver dysfunction. Combining intraoperative serum and liver tissue markers predicts subsequent PHLF. Cholangiocarcinoma patients demonstrated pronounced systemic and hepatic oxidative stress, with increasing levels in advanced tumor stages, thus representing a worthwhile target for future exploratory and therapeutic studies.

The antioxidant, anti-inflammatory and analgesic activity effect of ethyl acetate extract from the flowers of Syringa pubescens Turcz

Ethnopharmacological relevanceSyringa Pubescens Turcz. (SP), a member of the Oleaceae family, is a species of plant known as Syringa. Flowers, as the medicinal part, are commonly used in the treatment of hepatitis and tonsillitis.Aim of the study: The research was the first to assess the antioxidant and anti-inflammatory potential of different parts of SP flowers (SPF) in vitro. The most promising fraction was ethyl acetate fraction of SP flower (SPFEA). The antioxidant, anti-inflammatory and analgesic activities of SPFEA were further studied, and the chemical components were identified. MethodsHPLC was used to identify the major components in various fraction of SPF. DPPH and ABTS + radical scavenging assays as well as FRAP test and β-carotene bleaching test were employed to assess the antioxidant potential of SPF fraction in vitro. The inhibitory effect on NO production in LPS-treated RAW264.7 cells and heat-induced protein denaturation test were used to evaluate the anti-inflammatory potential of SPF fraction. Further analysis of the biological activity of SPFEA was performed. Acute toxicity test was conducted to assess the toxicity of SPFEA. The anti-inflammatory effect was assessed by utilizing xylene induced ear edema model, carrageenan-induced foot edema model and peritonitis model in vivo. The analgesic effect of SPFEA was evaluated using hot plate test, tail immersion test, formaldehyde test as well as acetic acid-induced abdominal writhing pain experiment in vivo. In carrageenan induced foot edema model, ELISA kits were employed to measure levels of inflammation factors (NO, TNF-α, IL-6, COX-2, IL-1β) in foot tissue as well as MDA, CAT, SOD, GSH-PX levels in liver tissue. ResultsHPLC results showed that there were significant differences in bioactive substances among different fractions of SPF, and SPFEA was rich in bioacitve components. Compared with other fractions of SPF, SPFEA exhibited better antioxidant and anti-inflammatory abilities. The 3000 mg/kg SPFEA group in mice had no obvious side effects. The xylene-induced ear edema model, carrageenan-induced foot edema and peritonitis models demonstrated that the SPFEA had significant anti-inflammatory effect. Moreover, inflammation factors including NO, TNF-α, IL-6, COX-2, IL-1β were significantly reduced in SPFEA groups in foot tissue induced by carrageenan. Additionally, SPFEA effectively decreased liver tissue oxidative stress levels (MDA, SOD, GSH-PX and CAT). The bioactivities of SPFEA demonstrated a clear dose-dependent relationship. The results of the hot plate test, tail immersion test, formaldehyde test and acetic acid-induced abdominal writhing pain experiments indicated the SPFEA possessed an excellent analgesic effect, and this effect was in dose-dependent manner. ConclusionThe study provides a scientific foundation for understanding the pharmacological action of SPFEA. It has been indicated that SPFEA has excellent antioxidant, analgesic and anti-inflammatory effects.

Down-regulation of Lon protease 1 lysine crotonylation aggravates mitochondrial dysfunction in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a prevalent reproductive endocrine disorder, with metabolic abnormalities and ovulation disorders. The post-translational modifications (PTMs) are functionally relevant and strengthen the link between metabolism and cellular functions. Lysine crotonylation is a newly identified PTM, the function of which in PCOS has not yet been reported. To explore the molecular mechanisms of crotonylation involved in the abnormalities of metabolic homeostasis and oocyte maturation in PCOS, by using liquid chromatography-tandem mass spectrometry analysis, we constructed a comprehensive map of crotonylation modifications in ovarian tissue of PCOS-like mouse model established by dehydroepiandrosterone induction. The crotonylation levels of proteins involved in metabolic processes were significantly decreased in PCOS ovaries compared to control samples. Further investigation showed that decrotonylation of Lon protease 1 (LONP1) at lysine 390 was associated with mitochondrial dysfunction in PCOS. Moreover, LONP1 crotonylation levels in PCOS were correlated with ovarian tissue oxidative stress levels, androgen levels, and oocyte development. Consistently, down-regulation of LONP1 and LONP1 crotonylation levels were also observed in the blood samples of PCOS patients. Collectively, our study revealed a mechanism by which the decrotonylation of LONP1 may attenuate its activity and alter follicular microenvironment to affect oocyte maturation in PCOS.

Changes in heavy metal levels, reproductive characteristics, oxidative stress markers and testicular apoptosis in rams raised around thermal power plant

Male reproductive dysfunction is one of the damages in the organism caused by heavy metals. In this study, it was aimed to investigate the changes in heavy metal levels in serum and testicular tissue, and serum hormone levels, epididymal spermatozoa characteristics, tissue oxidative stress levels, testicular histology and testicular apoptosis level in rams raised in remote and near regions of a thermal power plant. A total of 75 rams were divided into 3 groups according to the regions, where they were born and raised, being far [250 km distance, group 1 (control), n = 25], close (20 km distance, group 2, n = 25) and very close (10 km distance, group 3, n = 25) to the thermal power plant. The blood along with testis and epididymis tissues was taken from the animals after slaughtering. In addition, soil and water heavy metal analyzes were also performed. The highest levels of serum Al, Cr, As, Ag, Sn and testicular Al, V, Ni, Ag, Cd, Cr, As, Pb, and the lowest levels of serum Cu, testicular Cu and Zn were determined in group 3 compared to control. Soil and water heavy metal results were similar to those found in serum and testis. The lowest serum testosterone level, tissue glutathione-peroxidase and catalase activities, spermatozoon concentration, and the highest tissue malondialdehyde level, dead spermatozoon rate, Bax apoptotic protein expression level and Bax/Bcl-2 rate alongside some testicular histopathological lesions were found in group 3 in comparison to control. Significant correlations were determined between some heavy metal levels and some parameters measured. As a result, heavy metals accumulate in the soil and water in the region close to the thermal power plant. The endocrine and exocrine reproductive potentials of rams born and grown in these regions were clearly damaged by the increased testicular heavy metals due to water drank and herbs consumed.

The atherosclerosis-ameliorating effects and molecular mechanisms of BuYangHuanWu decoction

Atherosclerosis (AS) is one of the leading causes of cardiovascular disease and has a high rate of morbidity and mortality. Traditional Chinese Medicine (TCM) supplied many therapies for AS treatment for centuries. Among these treatments, BuYangHuanWu decoction (BYHWD) is a classic prescription. In this study, we analyzed the mechanisms of BYHWD in the treatment of AS by using a network pharmacology method. Our results revealed the mechanisms of BYHWD in treating AS, which is highly related to inflammation and apoptosis pathways, moreover, the genes including IL1β, TGFB1, TNF, IL6, NFκB1 are proved to be the key pharmacological targets for the treatment of AS. Furthermore, an AS rat model was established and the rats in the treatment group received different amounts of BYHWD. Serum lipid levels (TC/TG/HDL-C/LDL-C) and tissue oxidative stress levels (SOD, GSH-Px, CAT and MDA) were ameliorated in a dose-dependent manner. The morphology of the aortic intima in the BYHWD-treated groups was improved. Real-time PCR and Western blot analysis results indicated that inflammatory cytokines were suppressed and that the NF-κB signaling pathway was blocked by BYHWD. All of this evidence suggested that BYHWD is an ideal prescription for treating AS.

Safety parameters of in vivo low-energy shock waves and their impact on adult rat testes.

Low-energy shock waves (LESWs) have been widely used in the intervention of a subset of diseased tissues and organs with good results. However, it is unclear whether they can be used directly to intervene in the testes. Therefore, the aim of this study was to determine a relatively safe energy density and impulse number for rat testes. A total of 176 male rats were randomly and equally assigned to different intervention groups. Among them, 144 rats were assigned to 18 shock subgroups with different energy densities (0.02, 0.04 and 0.06mJ/mm2), different impulse numbers (500, 1000 and 1500 impulses) and different shock periods (2 and 8 weeks). The remaining 32 rats were divided into the sham intervention (S) groups and the blank control (N) groups with observation periods of 2 weeks and 8 weeks. One day after the last LESWs intervention, all the rats were weighed, and the concentrations of reproductive endocrine hormones were measured, the semen quality and testicular tissue oxidative stress levels were analyzed, and histomorphology and ultrastructures were observed. We found that there were no significant differences in the whole-body physiological state, testicular tissue morphology, oxidative stress state and sperm quality between the L1 shock group and the corresponding S group and N group (all p˃0.05, respectively). However, the other parameters of the shock groups caused different degrees of damage to the structure and function of rat testes, and the whole-body physiological state was also adversely affected. This study demonstrated that LESWs with an energy density of 0.02mJ/mm2 and 500 impulses had no adverse effects on the rat testes.

Scintigraphic evaluation of renoprotective effects of coenzyme Q10 in a rat renal ischemia-reperfusion injury.

Renal ischemia-reperfusion injury (RIRI) may occur secondary to several reasons leading to renal failure. Coenzyme-Q10 (CoQ10) is a well-known antioxidant. However, the effects CoQ10 against RIRI have not been evaluated. Our aim was to evaluate protective effects of CoQ10 to renal ischemia-reperfusion by biochemical, immunohistochemical and scintigraphic findings. Thirty Wistar-albino rats were randomly separated into groups of 10; Group Sham; Group ischemia-reperfusion (IR) had left renal pedicle clamping; Group CoQ10+IR had IR and CoQ10. Twenty-four hours later after reperfusion, scintigraphy was performed and after that, rats were sacrificed. To demonstrate effects of RIRI, serum urea and creatinine levels and tissue levels oxidative stress markers were evaluated. Both kidneys were subjected to histopathological evaluation and to confirm RIRI-induced immunohistochemical aspects of apoptosis, terminal-deoxynucleotidyl-transferase mediated-deoxyuridine-triphosphate-nick-end-labeling assay and caspase-3 were assessed. Tissue oxidative stress, histopathologic changes, apoptosis scores and quantitative scintigraphic parameters were significantly higher in Group IR compared with Group Sham. Although tissue oxidative stress levels and histopathologic changes were not significant, quantitative scintigraphic parameters of contralateral kidney of Group IR were significantly increased. Compared with Group IR, Group CoQ10+IR presented decreased tissue oxidative stress levels; decreased scores of histopathology and apoptosis; and decreased quantitative scintigraphic parameters with increased split renal function in ischemic kidney. Our results suggest that other than its antioxidant properties, CoQ10 shows antiperoxidative, antiapoptotic and antiinflammatory potential in protecting renal functioning of ischemic kidney. Furthermore, our results show that renal scintigraphy is a feasible method to detect early changes in renal functioning after RIRI.

Effects of l-Carnitine on the Follicle-Stimulating Hormone, Luteinizing Hormone, Testosterone, and Testicular Tissue Oxidative Stress Levels in Streptozotocin-Induced Diabetic Rats.

The present study was designed to investigate the antioxidant property of l-carnitine (LC) on serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (TH) and testis oxidative stress in streptozotocin (STZ)-induced diabetic rats. The rats were divided into the following groups: group I, control; group II, LC 100 mg/kg/d; group III, diabetic; and groups IV to VI, diabetic rats treated with 50, 100, and 200 mg/kg/d of LC, respectively. Daily injections were given intraperitoneally for 7 weeks. At the end of experimental period, after sacrificing the rats, FSH, LH, TH, total antioxidant capacity (TAC), malondialdehyde (MDA), glutathione (GSH), catalase (CAT), mitochondrial function (MTT), protein carbonyl (PC), and reactive oxygen species (ROS) levels were measured. STZ caused an elevation of MDA, ROS, and PC (P < .001) with reduction of GSH, CAT, TAC, and MTT (P < .001) in the serum levels. Group VI had significantly increased FSH, LH, and TH levels versus the untreated diabetic group (P < .001). Although groups V and VI significantly decreased MDA (P < .001), PC (P < .01), and ROS (P < .01) compared with the untreated diabetic group; only in group VI, the activity of GSH (P < .001), CAT (P < .01), TAC (P < .001), and MTT (P < .001) significantly increased. The results of the present study suggest that LC decreased diabetes-induced oxidative stress complications and also improved serum level of FSH, LH, and TH by reducing levels of lipid peroxidation and increasing antioxidant enzymes.

A Pilot Study Linking Endothelial Injury in Lungs and Kidneys in Chronic Obstructive Pulmonary Disease.

Patients with chronic obstructive pulmonary disease (COPD) frequently have albuminuria (indicative of renal endothelial cell injury) associated with hypoxemia. To determine whether (1) cigarette smoke (CS)-induced pulmonary and renal endothelial cell injury explains the association between albuminuria and COPD, (2) CS-induced albuminuria is linked to increases in the oxidative stress-advanced glycation end products (AGEs) receptor for AGEs (RAGE) pathway, and (3) enalapril (which has antioxidant properties) limits the progression of pulmonary and renal injury by reducing activation of the AGEs-RAGE pathway in endothelial cells in both organs. In 26 patients with COPD, 24 ever-smokers without COPD, 32 nonsmokers who underwent a renal biopsy or nephrectomy, and in CS-exposed mice, we assessed pathologic and ultrastructural renal lesions, and measured urinary albumin/creatinine ratios, tissue oxidative stress levels, and AGEs and RAGE levels in pulmonary and renal endothelial cells. The efficacy of enalapril on pulmonary and renal lesions was assessed in CS-exposed mice. Patients with COPD and/or CS-exposed mice had chronic renal injury, increased urinary albumin/creatinine ratios, and increased tissue oxidative stress and AGEs-RAGE levels in pulmonary and renal endothelial cells. Treating mice with enalapril attenuated CS-induced increases in urinary albumin/creatinine ratios, tissue oxidative stress levels, endothelial cell AGEs and RAGE levels, pulmonary and renal cell apoptosis, and the progression of chronic renal and pulmonary lesions. Patients with COPD and/or CS-exposed mice have pulmonary and renal endothelial cell injury linked to increased endothelial cell AGEs and RAGE levels. Albuminuria could identify patients with COPD in whom angiotensin-converting enzyme inhibitor therapy improves renal and lung function by reducing endothelial injury.

Protective effects of Hammada scoparia flavonoid-enriched fraction on liver injury induced by warm ischemia/reperfusion

Context: Hepatic ischemia/reperfusion injury (IRI) is a major cause of liver damage during liver surgery and transplantation. Plants have historically been used in treating liver damage, and Hammada scoparia (Pomel) (Chenopodiaceae) has been reported to possess a broad spectrum of pharmacological and therapeutic activities.Objective: In this study, a flavonoid-enriched fraction was used before the warm ischemia (WI) process as pharmacological preconditioning and in combination with technical postconditioning to evaluate their protective effects.Materials and methods: The rats were divided into five groups: a sham group; a control group (Control-IR) that was submitted to 60 min WI; a Pharmacological Preconditioning group (PreC-IR) that received flavonoid-enriched fraction (200 mg/kg body weight); a Postconditioning group (PostC) and a PreC + PostC group.Results: The use of the flavonoid-enriched fraction was noted to significantly (p < 0.05) reduce liver injury, as evidenced by the decrease in liver transaminase activities (AST and ALT) and lactic dehydrogenase (LDH), alkaline phosphatase (ALP), and lipid peroxidation (TBARS), levels as well as the enhancement of antioxidant enzymes (catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx)) responses. The results also indicated that, compared with the separate application of pharmacological preconditioning and postconditioning, the combination of both treatments was more effective in reducing tissue oxidative stress levels through modulating SOD, GSH-PX, and CAT activities. Furthermore, the combined protocol further decreased the liver morphological score compared with solo treatment.Discussion and conclusion: Overall, the results indicate that the H. scoparia flavonoid-enriched fraction could be a promising candidate for future application as a pharmacological preconditioning agent against hepatic IRI.

Oxidative stress and changes in the content and pattern of tissue expression of &amp;#946;-catenin protein in diversion colitis

OBJECTIVE: The aim of this study is to verify if oxidative stress is related to changes in content and pattern of β-catenin protein expression in an experimental model of diversion colitis. METHODS: Sixty Wistar rats were submitted to intestinal bypass. The animals were divided into three groups according to the sacrifice to take place in six, 12 and 18 weeks. For each group, five animals only underwent laparotomy (control). The presence of colitis was diagnosed by histological study, and its severity, by inflammation grading scale. Cellular oxidative stress was measured by comet assay. Tissue expression of β-catenin protein was analyzed by the immunohistochemistry and quantification of its tissue content by computerized morphometry. Statistical analysis was performed with the Student's t-test, median, Mann-Whitney, ANOVA and Kruskal-Wallis, adopting a significance level of 5% (p <0.05). RESULTS: Colon segments without fecal stream developed colitis, which worsened with time of exclusion. Segments without fecal stream suffer higher levels of oxidative stress when compared to those with stream, and it worsens with time of exclusion. The levels of cellular oxidative stress are directly related to the degree of inflammation. The total content of β-catenin in segments without fecal stream reduces after six weeks, and does not vary thereafter. The content of β-catenin in the apical portion of the colon crypts decreases with time, whereas in the basal region, it increases. The total content of β-catenin is inversely related to the degree of inflammation and levels of tissue oxidative stress levels. CONCLUSION: There are changes in tissue content of E-cadherin and increased expression of β-catenin in proliferative regions of colonic crypts, related with oxidative tissue stress.

Effects of epicatechin rich cocoa on REDUX status in human skeletal muscle

Increases in tissue oxidative stress levels are associated with alterations in mitochondrial structure/function. We performed a study in 5 heart failure, type 2 diabetes patients where treatment (Tx) with (−)‐epicatechin (Epi) rich cocoa led to the recovery of skeletal muscle (SkM) mitochondrial cristae and increases in markers of biogenesis. In this study we evaluated SkM levels of indicators of tissue oxidative stress before and after 3 months of treatment with Epi‐rich cocoa containing ~100 mg of Epi. Biopsy SkM samples were assayed for changes in total thiols, nytrotyrosine and carbonylation levels and compared to values obtained from SkM of normal subjects. Prior to Tx, there were significant decreases in levels of SkM thiols and increases in nitrotyrosine and carbonylation levels which were restored by the use of Epi‐rich cocoa to levels similar to controls. To understand the mechanisms underlying these changes, a mouse model of diabetes was used (high fat diet; HFD). Similar changes were observed in SkM thiols, nitrotyrosine and carbonylation levels which were restored by Epi Tx for 2 weeks (1 mg/kg BID). SkM levels of molecular regulators of reactive oxygen species metabolism (superoxide dismutase and catalase) were decreased with HFD and restored by Epi. These results indicate that Epi can apparently reverse metabolic alterations in SkM REDUX status by exerting effects on key enzymatic control systems.

Feeding Period of Selenium-Deficient Diet and Response of Redox Relating Minerals

Dynamics of redox relating biotrace elements, selenium (Se), iron (Fe), and zinc (Zn) in liver, kidney, and spleen of selenium deficient Wistar male rats in a series of feeding period (from 0 to 8 weeks) were studied using instrumental neutron activation analysis (INAA). Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and blood urea nitrogen (BUN) for the plasma fraction of the rat bloods and the concentration of vitamin C and vitamin E in the liver homogenates were measured. The initial purpose of this study was to find Fe and Zn as sensitive indices of the tissue oxidative stress levels. However, the relationships among the biotrace elements and the oxidative stress/injury were much complicated. Control group, which was fed Se-deficient diet with Na2SeO4 (0.1 mg selenium/l) in drinking water, showed strange response of Se and Zn contents in the kidney and showed high BUN. Supplementation of inorganic Se by biased Se source may serve as another source of a stress especially in the kidney. The Fe and Zn contents in the liver and kidney look sensitive to the Se-deficiency and/or relating oxidative stresses. Short term exposure to the Se-deficiency appeared to consume Fe and Zn in the liver and kidney. In contrast, long term or chronic exposure to Se-deficiency appeared to accumulate Fe and Zn in liver and kidney.