Resveratrol attenuates oxidative stress and histological alterations induced by liver ischemia/reperfusion in rats

AIM： To investigate the effects of resveratrol on liver ischemia/reperfusion （I/R） injury in rats. METHODS： A total of 40 male Sprague-Dawley rats weighing 240-290 g were randomized into four groups of ten： （1） controls： data from unmanipulated animals; （2） sham group： rats subjected to the surgical procedure, except for liver I/R, and given saline; （3） I/R group： rats underwent liver ischemia for 45 rain followed by reperfusion for 45 rain; （4） I-R/Resveratrol group： rats pretreated with resveratrol （10 umol/L, iv）. Liver tissues were obtained to determine antioxidant enzyme levels and for biochemical and histological evaluation. RESULTS： Plasma aminotransferase activities were higher in the I/R group than in the I-R/Resveratrol group. Malondialdehyde levels and the hepatic injury score decreased, while superoxide dismutase, catalase, and glutathione peroxidase levels increased in group 4 compared to group 3. In group 4, histopathological changes were significantly attenuated in resveratroltreated livers. CONCLUSION： These results suggest that resveratrol has protective effects against hepatic I/R injury, and is a potential therapeutic drug for ischemia reperfusionrelated liver injury.

Nitroglycerine effects on portal vein mechanics and oxidative stress in portal hypertension

AIM:Тo examine the effects of nitroglycerine on portal vein haemodynamics and oxidative stress in patients with portal hypertension.METHODS:Thirty healthy controls and 39 patients with clinically verified portal hypertension and increasedvascular resistance participated in the study.Liver di-ameters,portal diameters and portal flow velocities were recorded using color flow imaging/pulsed Doppler detection.Cross-section area,portal flow and index of vascular resistance were calculated.In collected blood samples,superoxide anion radical (O 2-),hydrogen per-oxide (H 2 O 2),index of lipid peroxidation (measured as TBARS) and nitric oxide (NO) as a marker of endothelial response (measured as nitrite-NO 2-) were determined.Time-dependent analysis was performed at basal state and in 10th and 15th min after nitroglycerine (sublingual 0.5 mg) administration.RESULTS:Oxidative stress parameters changed sig-nificantly during the study.H 2 O 2 decreased at the end of study,probably via O 2-mediated disassembling in Haber Weiss and Fenton reaction;O 2-increased signifi-cantly probably due to increased diameter and tension and decreased shear rate level.Consequently O 2-and H 2 O 2 degradation products,like hydroxyl radical,initi-ated lipid peroxidation.Increased blood flow was to some extent lower in patients than in controls due to double paradoxes,flow velocity decreased,shear rate decreased significantly indicating non Newtonian char-acteristics of portal blood flow.CONCLUSION:This pilot study could be a starting point for further investigation and possible implemen-tation of some antioxidants in the treatment of portal hypertension.

Doxycycline blocks gastric ulcer by regulating matrix metalloproteinase-2 activity and oxidative stress

AIM: To examine the effect of doxycycline on the activity of matrix metalloproteinases (MMPs) and oxidative stress in gastric tissues of rats following gastric injury.METHODS: Gastric ulcers were generated in rats by administration of 70% ethanol,and activity of doxycycline was tested by administration 30 min prior to ethanol.Similarly,the effect of doxycycline was tested in an indomethacin-induced gastric ulcer model.The activities and expression of MMPs were examined by zymography and Western blot analysis.RESULTS: Gastric injury in rats as judged by elevated ulcer indices following exposure to ulcerogen,either indomethacin or ethanol,was reversed significantly by doxycycline.Indomethacin-induced ulcerated gastric tissues exhibited about 12-fold higher proMMP-9 activity and about 5-fold higher proMMP-3 activity as compared to control tissues.Similarly,ethanol induced about 22-fold and about 6-fold higher proMMP-9 and proMMP-3 activities,respectively,in rat gastric tissues.Both proMMP-9 and MMP-3 activities were markedly decreased by doxycycline in ulcerogen treated rat gastric tissues.In contrast,the reduced MMP-2 activity in ulcerated tissues was increased by doxycycline during ulcer prevention.On the other hand,doxycycline inhibited significantly proMMP-9,-2 and -3 activities in vitro.In addition,doxycycline reduced oxidative load in gastric tissues and scavenged H2O2 in vitro.Our results suggest a novel regulatory role of doxycycline on MMP-2 activity in addition to inhibitory action on MMP-9 and MMP-3 during prevention of gastric ulcers.CONCLUSION: This is the first demonstration of dual action of doxycycline,that is,regulation of MMP activity and reduction of oxidative stress in arresting gastric injury.

Endurance exercise and gut microbiota:A review

Background: The physiological and biochemical demands of intense exercise elicit both muscle-based and systemic responses. The main adaptations to endurance exercise include the correction of electrolyte imbalance, a decrease in glycogen storage and the increase of oxidative stress, intestinal permeability, muscle damage, and systemic inflammatory response. Adaptations to exercise might be influenced by the gut microbiota, which plays an important role in the production, storage, and expenditure of energy obtained from the diet as well as in inflammation,redox reactions, and hydration status.Methods: A systematic and comprehensive search of electronic databases, including MEDLINE, Scopus, Clinical Trials.gov, Science Direct,Springer Link, and EMBASE was done. The search process was completed using the keywords: "endurance", "exercise", "immune response","microbiota", "nutrition", and "probiotics".Results: Reviewed literature supports the hypothesis that intestinal microbiota might be able to provide a measureable, effective marker of an athlete's immune function and that microbial composition analysis might also be sensitive enough to detect exercise-induced stress and metabolic disorders. The review also supports the hypothesis that modifying the microbiota through the use of probiotics could be an important therapeutic tool to improve athletes' overall general health, performance, and energy availability while controlling inflammation and redox levels.Conclusion: The present review provides a comprehensive overview of how gut microbiota may have a key role in controlling the oxidative stress and inflammatory responses as well as improving metabolism and energy expenditure during intense exercise.

Hydrogen gas:a novel antioxidant for chronic obstructive pulmonary disease?

Oxidative stress therapy targeted on ox plays idativ critical role in the pathogenesis of chronic obstructive e stress is of great importance for COPD. However, since pu the lmonary disease （COPD）, so current used antioxidants are not satisfying, scientists have to find more effective antioxidants for COPD. Hydrogen, the most abundant chemical element in the universe, was recently discovered as a novel therapeutic medical gas, and has shown great antioxidant potential in a series of recent published researches for its feature of selectively reducing toxic reactive oxygen species. Based on these findings, we hypothesize that hydrogen gas therapy might be a novel, effective, safe, and economic treatment for COPD patients in one day

Anti-Acute Fatigue Effects of Ethanol Extract of Bidens pilosa L.and the Profiling of Antioxidant Index in ICR Mice

The effects of ethanol extract of Bidens pilosa L.(EEB)on acute exercise fatigue and its underlying biochemical mechanism were investigated in this study.Sixty adult male ICR mice were divided into control,model,vitamin C(VC)100,EEB40,EEB80,and EEB160 groups,receiving VC(100 mg/kg)or EEB(40,80,160 mg/kg)for 28 days(intragastrically,I.G.).The mice underwent tailsuspension,elevated plus maze(EPM),rotarod,and loaded swimming tasks and biochemical indices were measured.There were no significant differences in body weight,tail suspension time,EPM open arm time/entries and serum cortisone levels among the groups.Compared with the model group,there was an increase in rotarod latency in the VC100/EEB80 groups and an increase in loaded swimming time in the EEB80/EEB160 groups.Furthermore,the haptic and muscle glycogen levels decreased in the model group,while the haptic glycogen levels increased in the all VC/EEB groups.Similarly,the serum lactate and creatinine levels increased in the model group,but decreased in lactate(except for EEB160),creatinine(except for EEB40)and lactate dehydrogenase in the EEB80 group.In the liver,malonaldehyde(MDA)and oxidized glutathione(GSSG)levels increased in the model group;however,glutathione reductase(GR)(except for EEB40),glutathione(GSH)and GSH/GSSG ratios increased,with GSSG levels decreasing in all VC/EEB groups.In the quadriceps,the GR levels increased in the model,whereas it decreased in the VC100,EEB40 and EEB80 groups.These results suggest that EEB has anti-acute fatigue effect,potentially attributed to mitigate metabolite accumulation,enhancing glycogen reserves,and fortifying the antioxidant mechanism.

Effects of (–)-5-hydroxy-equol on the lifespan and stress resistance of Caenorhabditis elegans

Caenorhabditis elegans （C. elegans） was used as an animal model to study the effect of （-）-5-hydroxy-equol, a microbialmetabolite of isoflavone genistein, on the lifespan, fecundity and resistance against thermal and oxidative stress. The resultsshowed that （-）-5-hydroxy-equol not only significantly increased the lifespan of C. elegans but also significantly enhancedthe resistance against thermal and oxidative stress at the concentrations of 0.1 mmol/L and 0.2 mmol/L. However, the fecundityof C. elegans was not obviously influenced after being exposed to the same concentrations of （-）-5-hydroxy-equol. Further studieson comparative transcriptome analyses and the lifespan ofdaf-16 （mu86） mutant and daf-2 （e1370） mutant indicated that（-）-5-hydroxy-equol prolonged the lifespan of C. elegans through DAF-2/DAF-16 Insulin/IGF-1 signaling pathway. This isthe first report that （-）-5-hydroxy-equol was able to increase the lifespan and improve the thermal and oxidative stress toleranceof C. elegans.

Individual and joint toxic effects of cadmium sulfate and α-naphthoflavone on the development of zebrafish embryo

This paper aims to evaluate the individual and joint toxicities of cadmium sulfate （CdSO4） and α-naphthoflavone （ANF） in zebrafish embryos. As a result, CdSO4 caused both lethal and sub-lethal effects, such as 24 h post-fertilization （hpf） death and 72 hpf delayed hatching. However, ANF only caused sub-lethal effects, including 48 hpf cardiac edema and 72 hpf delayed hatching. Taking 24 hpf death and 48 hpf cardiac edema as endpoints, the toxicities of CdSO4 and ANF were significantly enhanced by each other. Consistently, both CdSO4 and ANF caused significant oxidative stress, including decreases in the reduced glutathione （GSH） level, inhibition of superoxide dis- mutase （SOD） activity, as well as increases in malondialdehyde （MDA） content in zebrafish embryos, but these mixtures produced much more significant alterations on the biomarkers. Co-treatment of CdSO4 and ANF significantly down-regulated the mRNA level of multidrug resistance-associated protein （mrp） 1 and cytochrome P450 （cyp） la, which constituted the protective mechanisms for zebraflsh embryos to chemical toxins. In conclusion, co-treatment of CdSO4 and ANF exhibited a much more severe damage in zebraflsh embryos than individual treatment. Meanwhile, production of oxidative stress and altered expression of mrpl and cypla could be important components of such joint toxicity.

Effects of Polysaccharides Extracted from Zhu Zi Shen(Rhizoma Panacis Majoris) on Oxidative Stress and Hemodynamics in Rats with Adriamycin-induced Chronic Heart Failure

Objective:To probe into the intervening action of polysaccharides of Zhu Zi Shen(Rhizoma Panacis Majoris)(PZZS) on oxidative stress and hemodynamics in rats with adriamycin-induced chronic congestive heart failure(CHF).Methods:After SD rats were successfully modeled with adriamycin,they were randomly divided into a normal control group,a model group,a PZZS group,and a captopril group,and were administrated respectively.At the end of experiment,the hemodynamic function,whole heart weight index,and the blood CK,SOD,MDA,NO,NOS were detected;and the myocardial morphological examinations were carried out.Results:Compared with the normal control group,the arterial systolic pressure(SBP),diastolic pressure(DBP),mean arterial pressure(MAP),heart rate(HR),left ventricular systolic peak(LVSP),and left ventricular pressure change rate(dp/dtmax) significantly decreased,and left ventricular end diastolic pressure(LVEDP),whole heart weight index,the blood CK,MDA,NO,NOS significantly increased in the model group.PZZS significantly improved the hemodynamic function,lowered the MDA and NO levels,and decreased the CK and NOS activities in the CHF rats.Conclusion:PZZS can improve the hemodynamic function,and alleviate the oxidative stress reaction in the CHF rat.