Increased Oxygen Free Radical Research Articles

Mechanism of PGC-1α-mediated mitochondrial biogenesis in cerebral ischemia-reperfusion injury.

Cerebral ischemia-reperfusion injury (CIRI) is a series of cascade reactions that occur after blood flow recanalization in the ischemic zone in patients with cerebral infarction, causing an imbalance in intracellular homeostasis through multiple pathologies such as increased oxygen free radicals, inflammatory response, calcium overload, and impaired energy metabolism, leading to mitochondrial dysfunction and ultimately apoptosis. Rescue of reversibly damaged neurons in the ischemic hemispheric zone is the key to saving brain infarction and reducing neurological deficits. Complex and active neurological functions are highly dependent on an adequate energy supply from mitochondria. Mitochondrial biogenesis (MB), a process that generates new functional mitochondria and restores normal mitochondrial function by replacing damaged mitochondria, is a major mechanism for maintaining intra-mitochondrial homeostasis and is involved in mitochondrial quality control to ameliorate mitochondrial dysfunction and thus protects against CIRI. The main regulator of MB is peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), which improves mitochondrial function to protect against CIRI by activating its downstream nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM) to promote mitochondrial genome replication and transcription. This paper provides a theoretical reference for the treatment of neurological impairment caused by CIRI by discussing the mechanisms of mitochondrial biogenesis during cerebral ischemia-reperfusion injury.

A Comprehensive Review on Beneficial Effects of Catechins on Secondary Mitochondrial Diseases.

Mitochondria are the main sites for oxidative phosphorylation and synthesis of adenosine triphosphate in cells, and are known as cellular power factories. The phrase “secondary mitochondrial diseases” essentially refers to any abnormal mitochondrial function other than primary mitochondrial diseases, i.e., the process caused by the genes encoding the electron transport chain (ETC) proteins directly or impacting the production of the machinery needed for ETC. Mitochondrial diseases can cause adenosine triphosphate (ATP) synthesis disorder, an increase in oxygen free radicals, and intracellular redox imbalance. It can also induce apoptosis and, eventually, multi-system damage, which leads to neurodegenerative disease. The catechin compounds rich in tea have attracted much attention due to their effective antioxidant activity. Catechins, especially acetylated catechins such as epicatechin gallate (ECG) and epigallocatechin gallate (EGCG), are able to protect mitochondria from reactive oxygen species. This review focuses on the role of catechins in regulating cell homeostasis, in which catechins act as a free radical scavenger and metal ion chelator, their protective mechanism on mitochondria, and the protective effect of catechins on mitochondrial deoxyribonucleic acid (DNA). This review highlights catechins and their effects on mitochondrial functional metabolic networks: regulating mitochondrial function and biogenesis, improving insulin resistance, regulating intracellular calcium homeostasis, and regulating epigenetic processes. Finally, the indirect beneficial effects of catechins on mitochondrial diseases are also illustrated by the warburg and the apoptosis effect. Some possible mechanisms are shown graphically. In addition, the bioavailability of catechins and peracetylated-catechins, free radical scavenging activity, mitochondrial activation ability of the high-molecular-weight polyphenol, and the mitochondrial activation factor were also discussed.

Research Progress Based on Regulation of Tumor Microenvironment Redox and Drug-Loaded Metal-Organic Frameworks.

The process of tumor growth and deterioration is accompanied by increased oxygen free radicals, high glutathione concentration, hypoxia, and poor drug targeting during treatment, limiting the treatment of tumors. Metal-organic framework (MOF) preparations are continuously being developed and applied in tumor therapy. In this paper, the design and application of reactive oxygen species (ROS) and redox drug-loaded MOF preparations are reviewed. Moreover, the research challenges and application prospects of MOFs in tumor therapy are also discussed.

Study on scar repair and wound nursing of chitosan-based composite electrospun nanofibers in first aid of burn

Bacterial infection and oxidative stress are serious complications in emergency burn patients, as the increase of oxygen free radicals in burn wounds can aggravate vascular endothelial cell injury, make the wounds ischemic and hypoxic, and delay wound healing. Traditional dressings cannot meet the first-aid needs of burn patients. In this study, polycaprolactone/chitosan (PCL/CS) was used as an electrospun nanofiber matrix, and curcumin (CUR), a molecule with excellent anti-inflammatory and antioxidant properties, was introduced to construct polycaprolactone/ chitosan graft copolymer-zein-curcumin electrospun nanofibers (PCL/CS-ZE-CUR). The results of clinical experiments suggest that compared with traditional dressings, based on the excellent mechanical properties and antibacterial activity of PCL/CS, the new dressing can exhibit oxygen free radical-scavenging abilities of CUR to accelerate wound healing and is expected to provide a beneficial upgrade for wound emergency care.

Normobaric hyperoxia plays a protective role against renal ischemia-reperfusion injury by activating the Nrf2/HO-1 signaling pathway

Following renal ischemia-reperfusion injury (RIRI), because of the decrease in oxygen supply to the kidney, a large amount of oxygen-free radicals is generated, and in severe cases, tissue cells will undergo apoptosis or even die. Normobaric hyperoxia (NBHO) is a very common clinical adjuvant treatment. It restores the oxygen supply after renal ischemia and combats oxidative stress in tissues, thus playing a protective role. In this study, our aim is to elucidate the protective mechanism of NBHO inhalation in a rat RIRI model. We performed a surgical excision of the left kidney of the rat and established a right kidney solitary kidney model. Later, the right renal pedicle of the rat was clamped using a non-invasive vascular clamp for 45 min. After the vascular clamp was released and reperfused for 24 h, the rat was placed in a closed oxygen chamber. It was subjected to inhalation of high-concentration oxygen (50%–55%), 2 h daily, for 7 days.RIRI induces postoperative weight loss, impaired renal function, increased oxygen free radicals, reduced antioxidant substances, increased histopathological damage, and increased levels of apoptosis. These effects were significantly improved after treatment with NBHO. At the same time, NBHO significantly increased the expression levels of Nrf2 and HO-1 in the tissues after RIRI. To verify whether HO-1 induced by Nrf2 is involved in the resistance to oxidative stress, after the rat RIRI and before inhaling NBHO, we intraperitoneally injected HO-1 specific inhibitor zinc protoporphyrin (ZnPP) (45 μmol/Kg). However, we found that ZnPP reversed the protective effect of NBHO on RIRI in rats. Combining all the results, we have demonstrated the protective effect of NBHO on RIRI, which can be at least partially attributed to the activation of the Nrf2/HO-1 antioxidative stress pathway.

Association between Superoxide Dismutase 2 p.(Ala16Val) and Superoxide Dismutase 3 p.(Arg213Gly) Genetic Variants and Risk of Peripheral Neuropathy in Children and Adolescents with Type 1 Diabetes

Diabetic neuropathy (DN) is one of the microvascular complications of diabetes. Marked increase in oxygenfree radicals (OFR) results in oxidative stress that leads to development of DN. Antioxidant enzymes playa major role in protection against progression of DN, by reducing OFR. This study aimed to investigatethe association between superoxide dismutase 2 SOD2:p.(Ala16Val) and superoxide dismutase 3 SOD3:p.(Arg213Gly) genetic variants and the risk of neuropathy in Type 1 Diabetes children and adolescent. Thestudy included 80 children with type 1 diabetes divided into 2 groups, group 1 of 40 patients with clinicalDN and group 2 of 40 patients without DN. HbA1c levels were measured and genetic variants of SOD2:p.(Ala16Val) and SOD3:p.(Arg213Gly) were assessed by Taqman Real time Polymerase Chain Reaction(PCR) for both groups. The frequency of Ala/Ala genotype (OR=0.28 with 95% CI of 0.11-0.71) and Alaallele (OR=0.33 with 95% CI of 0.17-0.65) of SOD2:p. (Ala16Val) were significantly lower in group 1(27.5%, 50% respectively) than group 2 (57.5%, 75% respectively) (p=0.007, p=0.001 respectively). Incontrast the frequency of Val/Val genotype (OR=4.68 with 95% CI of 1.19-18.3) and Val allele (OR=3 with95% CI of 1.54-5.86) were significantly higher in group 1 (27.5%, 50% respectively) than group 2 (7.5%,25% respectively) (p=0.019 and p=0.001 respectively). Regarding SOD3:p.(Arg213Gly) gene variants thefrequency of Arg/Arg genotype and Arg allele were higher in group 1 (100%,100% respectively) than group2 (90%,95% respectively) but with statistical insignificance (P=0.06, P=0.058 respectively), however thefrequency of Arg/Gly genotype and Gly allele were higher in group 2 (10%, 5% respectively) than group 1(0%, 0% respectively) but also with no statistical significance (P=0.058 and P=0.06 respectively). There isa possible association between SOD2:p.(Ala16Val), but not with SOD3:p.(Arg213Gly) genetic variants andthe occurrence of DN in patients with type 1 diabetes mellitus.

Correlations between biomarkers of oxidative stress, glycemic control and insulin resistance in women with type 2 diabetes

Background. The main characteristic of type 2 diabetes mellitus (T2DM) is hyperglycemia due to insulin resistance. Enhanced oxidative stress owing to increased oxygen free radicals and/or reduced antioxidant defense has very important roles in T2DM development and also most of its complications. The aim of the current study was to evaluate correlations between biomarkers of oxidative stress, glycemic control and insulin resistance in women with T2DM. Materials and methods. Seventy nine women with T2DM were included in the current study and fasting blood samples were collected. Hemoglobin A1c (HbA 1c ); glucose; oxidative stress biomarkers including malodialdehyde, 8-isoprostane, catalase and total antioxidant capacity (TAC) were measured. The adiponectin/leptin (A/L) ratio and the homeostasis model assessment of beta-cell function (HOMA-B) were calculated. The results were considered significant when the p-value was less than 0.05. Results. Serum levels of TAC showed a significant positive correlation with the A/L ratio (r = 0.261, p = 0.02). A significant negative correlation was observed between values of HbA 1c and TAC (r = –0.300, p = 0.007). However, HbA 1c correlated positively with 8-isoprostane (r = 0.236, p = 0.036). Values of HOMA-B correlated negatively with values of HbA 1c (r = –0.327, p = 0.003). Serum levels of 8-isoprostane were significantly higher in obese (BMI > 30 kg/m 2 ) women than in non-obese (BMI < 30 kg/m 2 ) women (p = 0.032). Values of catalase (p = 0.022) and HOMA-B (p = 0.009) were significantly lower in women with HbA 1c ≥ 7.6% compared with women with HbA 1c < 7.6%. Conclusions. In summary, chronic hyperglycemia results in oxidative stress. This situation might lead to less beta cells function. In addition, low levels of the A/L ratio were associated with increased oxidative stress.

Hyperbaric oxygen treatment of spinal cord injury in rat model

BackgroundThe purpose of this study was to investigate the therapeutic effects and mechanisms of hyperbaric oxygen (HBO) treatment on rats following spinal cord injury (SCI).MethodsA total of 45 Sprague-Dawley (SD) rats were randomly divided into three groups. Sham-SCI group was surgically exposed but not subjected to the SCI procedure. SCI-control group was administered SCI and treated with regular air. SCI-HBO group was administered SCI and HBO treatment. Neuromotor functions were examined using the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and the inclined plane assessment at before SCI (baseline) and after SCI. Superoxide dismutase (SOD) activities and malondialdehyde (MDA) levels were measured.ResultsStarting from Day 1 after SCI but except Day 2, the SCI-HBO group has significantly higher BBB scores than the SCI-control group. After SCI, the maximum inclination angles at which rats could maintain were significantly lower in both SCI groups. But the maximum angles were significantly bigger for the rats in the SCI-HBO group than those on the SCI-control group at 5, 10 and 20 days after SCI. SOD activities in SCI-HBO rats were significantly higher and MDA levels were significantly lower than in SCI-control rats, at two and five days after SCI. There was also less cystic degeneration of spinal cord in SCI-HBO rats, compared to SCI-control rats.ConclusionsThese results suggest that HBO treatment has a therapeutic value in treating SCI. Increased oxygen free radical scavenging and reduced lipid oxidation may be one of the mechanisms.

Preventing oxygen free radical damage by proanthocyanidin in obstructive jaundice.

Tissue damage and endotoxemia in obstructive jaundice are attributed to the increase in oxygen free-radicals. We aimed at evaluating the possible protective effect of grape seed proanthocyanidin extract (GSPE), which is a potent exogenous free-radical scavenger and antioxidant. The study was performed at the Necmettin Erbakan University Meram School of Medicine Research and Application Center for Experimental Medicine Laboratory with ethical approval. 30 Wistar-Albino rats were used and were divided into 3 groups. The common bile duct was identified and only dissected in the first group (sham). Following dissection of the common bile duct it was ligated with 4/0 silk just above the pancreas in the second group (control). After ligation of the common bile duct, 100mg/kg/day GSPE was administered via orogastric lavage for 10 days in the third group. Biochemical values revealed a statistically significant difference between Group I and the others. There was no difference between Group II and III regarding biochemical values. There was a statistically significant difference, however, between Group II and III with regards to nitric oxide levels. There was a statistically significant difference between Group I and the other groups concerning hepatic and pulmonary tissue damage on histopathologic evaluation. There was no difference among the groups with regards to renal tubular damage. Proanthocyanidin is an effective natural antioxidant in decreasing the level of tissue damage caused by oxygen free-radicals.

Urinary metabolite profiling provides potential differentiation to explore the mechanisms of adjuvant-induced arthritis in rats.

To explore the pathogenesis of rheumatoid arthritis (RA) from the perspective of metabolomics, gas chromatography time-of-flight mass spectrometry (GC-TOF/MS) technology was used to observe changes in the metabolic profiles of urine output from rats with adjuvant-induced arthritis (AA). Sprague-Dawley rats were randomly divided into a control group and an experimental group, with eight in each. Rats in the experimental group were induced by intracutaneous innoculation of 0.1 mL Freund's complete adjuvant to right paws. On day 20 after immunization, the metabolic profiles between rat control and experimental groups were compared by combining GC-TOF/MS technology with multivariate statistical approaches, including principal component analysis, partial least squares discriminant analysis and orthogonal projections to latent structures-discriminant analysis. Nine potential biomarkers were identified, including 2,2-dimethylsuccinic acid, tartronic acid, dehydroshikimic acid, hippuric acid, adenine, phenaceturic acid, l-dopa, 1,4-dihydroxy-2-naphthoic acid and melibiose. The findings indicate that the rats with AA are disturbed in metabolism of purine, amino acid, fat and energy. This study also demonstrates that the dysfunction in a range of biosynthetic and catabolic pathways, which leads to increased oxygen free radicals and inflammation, could cause underlying pathogenesis of RA. Copyright © 2016 John Wiley & Sons, Ltd.

Airways oxidative stress, lung function and cognitive impairment in aging

An altered balance of oxidants/antioxidants is one of the pathological mechanisms of many age-dependent disorders. We aimed to investigate the age-related airways oxidative stress, using non invasive, safe and repeatable techniques; to evaluate the correspondence between systemic and local oxidative stress in healthy subjects of different age ranges; to analyse the correlation between systemic and local oxidative stress with lung function and with cognitive impairment. Thirty consecutive healthy high school graduated subjects (8 M, 22 F), divided in three ranges of age (< 35; between 35 and 60; > 60 years) were enrolled. All subjects underwent oxygen free radicals and exhaled nitric oxide measurement (by the diacron reactive oxygen metabolites test and by a rapid-response chemiluminescence nitric oxide analyzer), lung function tests, and cognitive impairment scales (Mini Mental State Examination and Geriatric Depression Scale). A significant increase of oxygen free radicals, exhaled nitric oxide, and Geriatric Depression Scale score and a significant decrease of forced expiratory volume in 1 second and forced expiratory vital capacity from younger to older subjects were identified. Moreover, the significant positive correlation between oxygen free radicals and exhaled nitric oxide, and between oxygen free radicals and exhaled nitric oxide with Geriatric Depression Scale score were found. The significant negative correlation between forced expiratory volume in 1 second and oxygen free radicals or exhaled nitric oxide was also demonstrated. Our data supports the role of progressive local oxidative stress in damaging the lung function and in inducing depression symptoms.

Effects of nitrogen dioxide and its acid mist on reactive oxygen species production and antioxidant enzyme activity in Arabidopsis plants

Nitrogen dioxide (NO2) is one of the most common and harmful air pollutants. To analyze the response of plants to NO2 stress, we investigated the morphological change, reactive oxygen species (ROS) production and antioxidant enzyme activity in Arabidopsis thaliana (Col-0) exposed to 1.7, 4, 8.5, and 18.8mg/m3 NO2. The results indicate that NO2 exposure affected plant growth and chlorophyll (Chl) content, and increased oxygen free radical (O2−) production rate in Arabidopsis shoots. Furthermore, NO2 elevated the levels of lipid peroxidation and protein oxidation, accompanied by the induction of antioxidant enzyme activities and change of ascorbate (AsA) and glutathione (GSH) contents. Following this, we mimicked nitric acid mist under experimental conditions, and confirmed the antioxidant mechanism of the plant to the stress. Our results imply that NO2 and its acid mist caused pollution risk to plant systems. During the process, increased ROS acted as a signal to induce a defense response, and antioxidant status played an important role in plant protection against NO2/nitric acid mist-caused oxidative damage.

In vitro incubation of human spermatozoa promotes reactive oxygen species generation and DNA fragmentation.

The aim of this study was to investigate the oxidative process associated with sperm capacitation and its impact on DNA fragmentation and sperm function. Redox activity and lipid peroxidation were analysed in human spermatozoa after 3, 6 and 22h of incubation in Ham's F10 medium plus bovine albumin at 37° and 5% CO2 for capacitation. DNA status, tyrosine phosphorylation pattern and induced acrosome reaction were evaluated after capacitating conditions. At 22h of incubation, there was a significant (P<0.05) increase in oxygen-free radicals and lipid peroxidation, with no effect on sperm viability. There also was a significant (P<0.001) increase in fragmented DNA in capacitated spermatozoa compared to semen values with higher rates being found after the occurrence of the induced acrosome reaction. Protein tyrosine phosphorylation pattern confirms that capacitation took place in parallel with the occurrence of DNA fragmentation. These results indicate that when spermatozoa are incubated for several hours (22h), a common practice in assisted reproductive techniques, an increase in oxidative sperm metabolism and in the proportion of fragmentedDNA should be expected. However, there was no effect on any of the other functional parameters associated with sperm fertilising capacity.

Pharmacological Strategies to Prevent Contrast-Induced Acute Kidney Injury

Contrast-induced acute kidney injury (CI-AKI) is the most common iatrogenic cause of acute kidney injury after intravenous contrast media administration. In general, the incidence of CI-AKI is low in patients with normal renal function. However, the rate is remarkably elevated in patients with preexisting chronic kidney disease, diabetes mellitus, old age, high volume of contrast agent, congestive heart failure, hypotension, anemia, use of nephrotoxic drug, and volume depletion. Consequently, CI-AKI particularly in high risk patients contributes to extended hospitalizations and increases long-term morbidity and mortality. The pathogenesis of CI-AKI involves at least three mechanisms; contrast agents induce renal vasoconstriction, increase of oxygen free radicals through oxidative stress, and direct tubular toxicity. Several strategies to prevent CI-AKI have been evaluated in experimental studies and clinical trials. At present, intravascular volume expansion with either isotonic saline or sodium bicarbonate solutions has provided more consistent positive results and was recommended in the prevention of CI-AKI. However, the proportion of patients with risk still develops CI-AKI. This review critically evaluated the current evidence for pharmacological strategies to prevent CI-AKI in patients with a risk of developing CI-AKI.

Oxidative Stress and Some Liver Functions Parameters in Patients with Symptomatic Cholelithiasis

Background : Gallstone disease is one of a common surgical problem and one of the most common gastrointestinal diseases throughout the world but its pathogenesis remains unclear. Many theories have been put forward to explain the mechanism of stone formation. The living organism has enzymatic and non-enzymatic antioxidant systems neutralizing the harmful effects of the endogenous oxygen free radicals products. Under certain conditions, the oxidative or anti-oxidative balance shifts towards the oxidative status as a result of increase in oxygen free radicals and/or impairment in antioxidant mechanism.&#x0D; Objective :To evaluate the oxidative stress markers (total antioxidants capacity and malondialdehyde) and some liver functions parameters (aspartate aminotransefrerase , alanin aminotranseferase , alkaline phosphatase , total serum bilirubin )in serum of patients with gallstone disease and in control group.&#x0D; Patients &amp; Methods : The study group included 75 patient with gallstone disease and 33 age- and sex-matched healthy volunteers as control group. Antioxidative status of serum was evaluated by measuring total antioxidant capacity . serum: malondialdehde , aspartate aminotranseferase , alanine aminotransferase , alkaline phosphatase, and total bilirubin, were all measured in serum of patients with gallstones and controls.&#x0D; Results : There was a significant increase(P&lt;0.05) in serum: malondialdehyde, alkaline phosphatase , alanin aminotranseferase ,aspartate aminotransefrerase , total serum bilirubin levels in patients with symtomatic gallstones compared to healthy controls. The study also showed that there was a significant decrease in serum total antioxidant capasity (P&lt;0.05) in the patients compared to control group .&#x0D; Conclusion : The present study results indicated that patients with gallstones may have been exposed to oxidative stress . change in liver functions parameters was also seen in serum of patients compared to controls . these findings may provides insights and helps in understanding the various biochemical alterations undergoing in the gallbladder responsible for stone formation and would be helpful in developing strategies for the treatment and prevention of gallstones.

Increased oxygen free radical production during pregnancy may impair vascular reactivity in preeclamptic women

To determine whether enhanced oxidative stress during pregnancy impairs vascular endothelial function and improves after delivery in preeclamptic women, we measured serum parameters of oxidative stress and endothelial function during pregnancy and 1 month after delivery in women with or without preeclampsia. We evaluated 18 participants with uncomplicated pregnancies, 11 with mild preeclampsia and 13 with severe preeclampsia. The plasma concentrations of reactive oxygen metabolite derivatives (d-ROMs) were measured, and the biological antioxidant potential (BAP) was determined to evaluate the oxygen free radicals and antioxidants, respectively. Flow-mediated vasodilation (FMD) was also assessed as a marker of endothelial function. FMD was decreased significantly in both preeclamptic groups compared with control during pregnancy. FMD did not change after delivery in the control group, but it significantly increased after delivery in both the mildly and severely preeclamptic groups, nearing control levels 1 month after delivery (mild, 6.5±3.6-9.0±3.5%; severe, 4.3±3.3-9.7±2.6%). No changes in d-ROM concentrations were observed in the control group; however, the concentrations in both the mildly and severely preeclamptic groups significantly decreased to normal levels 1 month after delivery (mild, 562.0±106.5-430.5±90.5 CARR U (Carratelli units); severe, 681.0±239.0-411.8±69.7 CARR U). The plasma BAP levels did not change significantly in all three groups. A negative correlation between FMD and d-ROM concentrations was observed in the preeclamptic group, but not in the control group (r=-0.497; P<0.05). Our findings indicated that enhanced oxidative stress during pregnancy may impair endothelial function and improve after delivery in preeclamptic women.

Effect of rapid temperature change on expression of hsp70 and hsp90 in grass carp(Ctenopharyngodon idella)

Grass carp(Ctenopharyngodon idella)is one of the most important cultured fishes in China.During transportation in summer,massive mortality often occurs.As molecular chaperones,Hsps assist cells in their recovery from stress and promote cytoprotection.Limited reports described the expression of Hsps in grass carp at high temperatures,and the relationship between oxygen consumption,expression of heat shock protein and mortality needs to be investigated based on the oxygen-and capability-limited thermal tolerance theory(OCLTT)to further elucidate the thermal adaptation of this species to high temperature in view of integrated biology.In the present study,the expressions of hsp70 and hsp90 after rapid temperature increase were studied.Grass carps were acclimated at 20 ℃ and then exposed to designated temperatures(20,22,24,26,28,30,32,34 ℃)for 3 h heat shock.After 2 h-recovery at 20 ℃,liver,muscle and gill of tested fish were sampled and hsp70 and hsp90 were determined using semi-quantitive real-time PCR.Expression of hsps increased with temperature increase until 32 ℃ in muscle and gill,and then decreased at 34 ℃.In liver,expression of hsps kept increasing in all temperature treatments.These results indicated that hsp70 and hsp90 were sensitive to temperature increase in grass carp.Analyzed heat shock proteins data with previous results of oxygen consumption and lethal temperatures of grass carp,the physiological adaptations of grass carp could be explained by oxygen-and capability-limited thermal tolerance theory(OCLTT),which pointed out that the imbalance between oxygen demand and tissue oxygen supply ability was the primary factor which limited organisms' thermal tolerance and the ability of aerobic metabolism greatly limited the survival of organism beyond critical temperatures.With temperature increase,the maximum value of oxygen consumption in grass carp occurred at 28 ℃,and then the oxygen consumption decreased when temperature was beyond 28 ℃,indicating a transformation from aerobic metabolism to anaerobic metabolism at this critical temperature.The expressions of heat shock proteins kept increasing until 32 ℃ in muscle and gill in grass carp,and provided defense against high temperature.However,this protection of heat shock proteins was limited and then death occurred when temperature was beyond 32 ℃.The change of metabolism,increase of oxygen free radicals and the consumption of energy due to stress proteins synthesis of grass carp were closely related to the decrease of capability of immune response when water temperature was beyond 28 ℃.In general,high water temperature could alter the metabolic pathway,induce heat shock protein expression,reduce immune response,and then cause large-scale mortality.Therefore,appropriate ways should be applied to maintain water temperature under 28 ℃ to avoid large-scale mortality during transportation.

Metabolic correction in the management of diabetic peripheral neuropathy: improving clinical results beyond symptom control.

Current Clinical Management Guidelines of Diabetic Peripheral Neuropathy (DPN) are based on adequate glucose control and symptomatic pain relief. However, meticulous glycemic control could delay the onset or slow the progression of diabetic neuropathy in patients with DM type 2, but it does not completely prevent the progression of the disease. Complications of DPN as it continues its natural course, produce increasing pain and discomfort, loss of sensation, ulcers, infections, amputations and even death. In addition to the increased suffering, disability and loss of productivity, there is a very significant economic impact related to the treatment of DPN and its complications. In USA alone, it has been estimated that there are more than 5,000,000 patients suffering from DPN and the total annual cost of treating the disease and its complications is over $10,000 million dollars. In order to be able to reduce complications of DPN, it is crucial to improve or correct the metabolic conditions that lead to the pathology present in this condition. Pathophysiologic mechanisms implicated in diabetic neuropathy include: increased polyol pathway with accumulation of sorbitol and reduced Na+/K+-ATPase activity, microvascular damage and hypoxia due to nitric oxide deficit and increased oxygen free radical activity. Moreover, there is a decrease in glutathione and increase in homocysteine. Clinical trials in the last two decades have demonstrated that the use of specific nutrients can correct some of these metabolic derangements, improving symptom control and providing further benefits such as improved sensorium, blood flow and nerve regeneration. We will discuss the evidence on lipoic acid, acetyl-L-carnitine, benfotiamine and the combination of active B vitamins L-methylfolate, methylcobalamin and piridoxal-6-phosphate. In addition, we discuss the role of metformin, an important drug in the management of diabetes, and the presence of specific polymorphic genes, in the risk of developing DPN and how metabolic correction can reduce these risks.

Effects of hydrogen-rich water on abnormalities in a SHR.Cg-Leprcp/NDmcr rat - a metabolic syndrome rat model

BackgroundHydrogen (H2), a potent free radical scavenger, selectively reduces the hydroxyl radical, which is the most cytotoxic of the reactive oxygen species (ROS). An increase in oxygen free radicals induces oxidative stress, which is known to be involved in the development of metabolic syndrome. Therefore, we investigated whether hydrogen-rich water (HRW) affects metabolic abnormalities in the metabolic syndrome rat model, SHR.Cg-Leprcp/NDmcr (SHR-cp).MethodsMale SHR-cp rats (5 weeks old) were divided into 2 groups: an HRW group was given oral HRW for 16 weeks, and a control group was given distilled water. At the end of the experiment, each rat was placed in a metabolic cage for 24 h, fasted for 12 h, and anesthetized; the blood and kidneys were then collected.ResultsSixteen weeks after HRW administration, the water intake and urine flow measured in the metabolic cages were significantly higher in the HRW group than in the control group. The urinary ratio of albumin to creatinine was significantly lower and creatinine clearance was higher in the HRW group than in the control group. After the 12-h fast, plasma urea nitrogen and creatinine in the HRW group were significantly lower than in the control group. The plasma total antioxidant capacity was significantly higher in the HRW group than in the control group. The glomerulosclerosis score for the HRW group was significantly lower than in the control group, and a significantly positive correlation was observed between this score and plasma urea nitrogen levels.ConclusionThe present findings suggest that HRW conferred significant benefits against abnormalities in the metabolic syndrome model rats, at least by preventing and ameliorating glomerulosclerosis and creatinine clearance.

A New Hypothesis of Pathogenesis Based on the Divorce between Mitochondria and their Host Cells: Possible Relevance for Alzheimers Disease

On the basis of not only the endosymbiotic theory of eukaryotic cell organization and evolution but also of observations of transcellular communication via Tunneling NanoTubes (TNTs), the hypothesis is put forward that when mitochondria, which were once independently living prokaryote-like organisms, are subjected to detrimental genetic, toxic, or environmental conditions, including age-related endogenous factors, they can regress towards their original independent state. At that point, they can become potentially pathogenic intruders within their eukaryotic host cell. Because of the protoplasmic disequilibrium caused by an altered, or mutated, mitochondral population, certain host cells with a minimal capacity for self-renewal, such as dopaminergic neurons, risk a loss of function and degenerate. It is also proposed that altered mitochondria, as well as their mutated mtDNA, can migrate, via TNTs, into adjacent cells. In this way, neurodegenerative states are propagated between cells (glia and/or neurons) of the Central Nervous System (CNS) and that this leads to conditions such as Alzheimer's and Parkinson's disease. This proposal finds indirect support from observations on rotenone-poisoned glioblastoma cells which have been co-cultured with non-poisoned cells. Immunocytochemical techniques revealed that mitochondria, moving along the TNTs, migrated from the poisoned cells towards the healthy cells. It has also been demonstrated by means of immunocytochemistry that, in glioblastoma cell cultures, Amyloid Precursor Protein (APP) is present in TNTs, hence it may migrate from one cell to neighbouring cells. This datum may be of high relevance for a better understanding of Alzheimer's Disease (AD) since molecular, cellular, and animal model studies have revealed that the formation of amyloid beta (Abeta) and other derivatives of the APP are key pathogenic factors in AD, causing mitochondrial dysfunction, free radical generation, oxidative damage, and inflammation. Furthermore, the present data demonstrate the presence of alpha-synuclein (alpha-syn) within TNTs, hence a similar pathogenic mechanism to the one surmised for AD, but centred on alpha-syn rather than on Abeta, may play a role in Parkinson's Disease (PD). As a matter of fact, alpha-syn can enter mitochondria and interact with complex I causing respiratory deficiency and increased oxygen free radical production. In agreement with this view, it has been demonstrated that, in comparison with normal subjects, PD patients show a significant accumulation of alpha-syn at Substantia Nigra and Striatal level, predominantly associated with the inner mitochondrial membrane,. These observations suggest that potentially neuropathogenic proteins, such as Abeta and alpha-syn, can not only diffuse via the extracellular space but also move from cell to cell also via TNTs where they can cause mitochondrial damage and cell degeneration. A mathematical model (see Appendix) is proposed to simulate the pathogenic consequences of the migration of altered mitochondria and/or of their mtDNA via TNTs. The results of the present simulation is compatible with the proposal that mutated mitochondrial agents behave as though they were infectious particles migrating through a continuum of interconnected cells.