Increase In Lipid Hydroperoxides Research Articles

AAPH-oxidised whey protein isolate forms a weak interfacial layer and promotes lipid oxidation in oil-in-water emulsions

The objective of this work was to investigate the interfacial adsorption properties and lipid oxidation of oil-in-water (O/W) emulsions prepared by 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) oxidised whey protein isolate (WPI) with different oxidation degrees. The results indicated that as the AAPH concentration increased, the degree of oxidation of WPI also increased significantly, as confirmed by the higher protein carbonyl and N'-formyl-L-kynurenine levels. AAPH interacted with WPI mainly through hydrogen bonding and hydrophobic interactions. Higher AAPH concentration changed the structure of WPI, which verified by the results of intrinsic tryptophan fluorescence, circular dichroism spectra and SDS-PAGE. Moreover, the ζ-potential and adsorbed proteins of O/W emulsions prepared by oxidised-WPI decreased with increasing degree of protein oxidation, but the droplet size of O/W emulsions increased. In addition, higher oxidation degrees of oxidised-WPI promoted lipid oxidation of O/W emulsions, reflected by an increase in lipid hydroperoxide and malondialdehyde levels. These findings indicated that oxidised WPI could lead to quality deterioration of O/W emulsions, especially for those with a higher degree of oxidation.

Transcriptome analysis reveals the oxidative damage and immune-suppression of leech (Whitmania pigra Whitman) intestine induced by high-temperature stress

Temperature is a key component in regulating the survival and growth of aquatic animals. However, the mechanism of high-temperature stress in Whitmania pigra Whitman has received little attention. Therefore, the aim of this study was to investigate the possible mechanisms of high-temperature stress in W. pigra using transcriptome analysis and detection of antioxidant markers. Samples were collected at 1 d, 3 d, 5 d, and 7 d under stress in two experimental groups: the control group at 27 °C and the high-temperature stress group at 35 °C. High-temperature stress caused oxidative damage in the leech intestine, as indicated by decreased antioxidant enzyme activities (superoxide dismutase and total antioxidant capacity) and increased lipid hydroperoxide malondialdehyde. Transcriptome analysis revealed 425 DEGs in leech intestine during high-temperature stress, with 275 up-regulated and 150 down-regulated genes. According to KEGG enrichment analysis, 425 DEGs were involved in the immune system and induced abnormal expression of disease-related genes. Furthermore, when leeches were exposed to high-temperature stress, B-cell lymphoma-2, heat shock protein 70, heat shock protein 90, and nuclear factor erythroid 2-related factor 2 mRNAs were dramatically upregulated, whereas activating transcription factor, inhibitor of Nuclear factor kappa-B, sequestosome 1, and toll-like receptor 4 mRNAs were significantly downregulated. In conclusion, 35 °C high-temperature stress impaired leech intestinal function by decreasing antioxidant capacity, causing oxidative damage, and suppressing the activation of immune capacity. This study contributes to future research on the detailed mechanisms of high-temperature stress in leeches.

Free Radical Oxidation and Metabolic Processes of Cartilage and Bone Tissues in Animals with Surgical Model of Posttraumatic Osteoarthrosis

INTRODUCTION: Posttraumatic osteoarthrosis (PTOA) resulting from injuries of connective-tissue components of the joint, is accompanied by formation of free radicals activating chondro- and osteoresorption, which leads to fragmentation of biopolymers of the extracellular matrix of the joint tissues.
 AIM: To study the peculiarities of free radical oxidation and metabolic processes of cartilage and bone tissues in animals with a surgical model of PTOA of the knee joint.
 MATERIALS AND METHODS: The study was conducted on 31 rats (11 intact animals and 20 animals with PTOA model). The metabolic processes of the connective tissue were evaluated by the changes in the content of biomarkers of the cartilage (hyaluronan, aggrecan) and bone (fibroblast growth factor-23, osteprotegerin, sclerostin, osteocalcin) tissues. The condition of the free radical oxidation processes was evaluated by the level of lipid hydroperoxides, and the activity of antioxidant system by the parameters of the total antioxidant and thiol statuses.
 RESULTS: In rats with the PTOA model, an increase in cartilage tissue biopolymers aggrecan and hyaluronan (p 0.001) was noted with a negative change in the marker of bone formation (a tendency to increase in the content of osteocalcin) and markers of regulation of bone homeostasis (increased fibroblast growth factor-23, p 0.001), with a tendency to decrease in the content of osteoprotegerin and sclerostin, in comparison with intact animals of the control group. In parallel with this, an increase in lipid hydroperoxides (p 0.01) in the systemic bloodstream was detected with a decrease in the thiol status index (p 0.01) with preserved normal total antioxidant activity (p 0.05).
 CONCLUSION: The data of the conducted study evidences intensification of free radical oxidation and derangement of metabolic processes in the bone and cartilage tissues in animals with a surgical model of PTOA of the knee joint. A negative change in the metabolism of the bone tissue was manifested by the loss of balance of remodeling processes, and metabolic disorders in the cartilage tissue consisted in the destruction of its biopolymers in conditions of intensification of free radical oxidation processes and relative tension of the thiol system with the total antioxidant activity remaining within the physiological norm. The established facts are promising from the point of view of using the studied biomarkers both for the identification of pathogenetic triggers of PTOA of the knee joint, and for the determination of the direction of therapeutic measures.

THE ANTIOXIDANT PROTECTION SYSTEM STATE OF RATS UNDER EXPERIMENTAL DOXORUBICIN INTOXICATION AND THE EFFECTS OF CORRECTING FACTORS

Introduction. The doxorubicin model was used for research, which, according to many authors, most adequately reproduces heart failure of varying degrees of severity. Doxorubicin is an antibiotic that has a cytostatic effect. The mechanism of its action consists of interaction with DNA, formation of free radicals, and inhibition of nucleic acid synthesis. The doxorubicin action and the development of hypoxia are accompanied by the activation of oxidative stress, the strengthening of free radical processes, and changes in the metabolism of carbohydrates, proteins, and lipids.
 The aim of the study – the effect of the drug “Bendamine” on the indicators of antioxidant protection of the body of rats under experimental simulation of heart failure.
 Research Methods. Modeling of heart failure was performed on sexually mature male Wistar rats with a body weight of 180–200 g. In blood and myocardial homogenate, the level of lipid peroxidation products, the activity of antioxidant enzymes, and the level of reduced glutathione were determined against the background of doxorubicin intoxication and when using the drug “Bendamine”.
 Results and Discussion. During doxorubicin intoxication, LPO processes are enhanced in rats, which is indicated by the increased lipid hydroperoxides, diene conjugates, and TBA-active products in the blood and the homogenate of the rat myocardium of the first experimental group. It is worth noting that the inhibition of the antioxidant defense system was also established in intoxicated rats, as indicated by the low level of both enzymatic and non-enzymatic links of the antioxidant system. It was established that bendamine has a corrective effect on rats' oxidative stress conditions inherent in doxorubicin-induced heart failure. The drug “Bendamine” inhibits the excessive formation of POL products in pathologically changed tissues of the heart of rats and has an inducing effect on the system of antioxidant protection.
 Conclusions. The influence of the drug "Bendamine" on the indicators of antioxidant protection of the body of rats under experimental simulation of heart failure was studied. Its antioxidant properties have been proven.
 
 

A Rodent Model of Human-Dose-Equivalent 5-Fluorouracil: Toxicity in the Liver, Kidneys, and Lungs.

5-Fluorouracil (5-FU) is a chemotherapy drug widely used to treat a range of cancer types, despite the recurrence of adverse reactions. Therefore, information on its side effects when administered at a clinically recommended dose is relevant. On this basis, we examined the effects of the 5-FU clinical treatment on the integrity of the liver, kidneys, and lungs of rats. For this purpose, 14 male Wistar rats were divided into treated and control groups and 5-FU was administered at 15 mg/kg (4 consecutive days), 6 mg/kg (4 alternate days), and 15 mg/kg on the 14th day. On the 15th day, blood, liver, kidney, and lung samples were collected for histological, oxidative stress, and inflammatory evaluations. We observed a reduction in the antioxidant markers and an increase in lipid hydroperoxides (LOOH) in the liver of treated animals. We also detected elevated levels of inflammatory markers, histological lesions, apoptotic cells, and aspartate aminotransferase. Clinical treatment with 5-FU did not promote inflammatory or oxidative alterations in the kidney samples; however, histological and biochemical changes were observed, including increased serum urea and uric acid. 5-FU reduces endogenous antioxidant defenses and increases LOOH levels in the lungs, suggesting oxidative stress. Inflammation and histopathological alterations were also detected. The clinical protocol of 5-FU promotes toxicity in the liver, kidneys, and lungs of healthy rats, resulting in different levels of histological and biochemical alterations. These results will be useful in the search for new adjuvants to attenuate the adverse effects of 5-FU in such organs.

Maternal dietary zinc status alters offspring female mammary gland development and response to acute 7,12-dimethylbenzanthracene insult

ABSTRACT We evaluated the effects of prenatal and postnatal dietary zinc (Zn) deficiency or supplementation on mammary gland morphology and on acute response to 7,12-dimethylbenzanthracene (DMBA) in pubertal female rats. On gestational day 10 (GD 10), rat dams were allocated randomly into three experimental groups of 10: a Zn-adequate diet group (ZnA) fed 35 mg Zn/kg chow, a Zn-deficient diet group (ZnD) fed 3 mg ZN/kg chow and a Zn-supplemented diet group (ZnS) fed 180 mg Zn/kg chow. After weaning, female offspring were fed the same diet as their dams until postnatal day 53 (PND 53). All animals received a single 50 mg/kg dose of DMBA on PND 51 and were euthanized on PND 53. Female ZnD offspring exhibited significantly less weight gain compared to the ZnA group and reduced mammary gland development compared to the ZnD and ZnA groups. By PND 53, the Ki-67 labeling index in mammary gland epithelial cells was significantly greater for the ZnS group than for the ZnA and ZnD groups. Apoptosis and ER-α indices did not differ among groups. The ZnD group exhibited significantly increased lipid hydroperoxide (LOOH) levels and decreased catalase and glutathione peroxidase (GSH-Px) activity compared to the ZnA and ZnS groups. The ZnS group exhibited significantly reduced superoxide dismutase (SOD) activity compared to the ZnA and ZnS groups. We observed atypical ductal hyperplasia in the mammary gland of female ZnS group offspring compared to the ZnA and ZnD groups and decreased expression of the Api5 and Ercc1 genes related to apoptosis inhibition and DNA damage repair, respectively. Both the Zn-deficient and Zn-supplemented diet exerted adverse effects on offspring mammary gland morphology and acute response to DMBA.

Lipid peroxidation and sphingolipid alterations in the cerebral cortex and hypothalamus of rats fed a high-protein diet

ObjectivesHigh-protein diets (HPDs) are widely accepted to enhance satiety and energy expenditure and thus have become a popular strategy to lose weight and facilitate muscle protein synthesis. However, long-term high-protein consumption could be linked with metabolic and clinical problems such as renal and liver dysfunctions. This study verified the effects of 8-wk high-protein ingestion on lipid peroxidation and sphingolipid metabolism in the plasma, cerebral cortex, and hypothalamus in rats. MethodsImmunoenzymatic and spectrophotometric methods were applied to assess oxidation-reduction (redox) biomarkers and neutral sphingomyelinase activity, whereas gas-liquid chromatography and high-performance liquid chromatography were used to examine sphingolipid levels. ResultsThe vast majority of HPD-related alterations was restricted to the hypothalamus. Specifically, an increased rate of lipid peroxidation (increased lipid hydroperoxides, 8-isoprostanes, and thiobarbituric acid reactive substances) associated with ceramide accumulation via the activation of de novo synthesis (decreased sphinganine), salvage pathway (decreased sphingosine), and sphingomyelin hydrolysis (decreased sphingomyelin and increased neutral sphingomyelinase activity) was noted. ConclusionsThis study showed that HPD substantially affected hypothalamic metabolic pathways, which potentially alter cerebral output signals to the peripheral tissues.

The Emerging Role of Noncoding RNA Regulation of the Ferroptosis in Cardiovascular Diseases.

Cardiovascular disease (CVD) is a significant public health issue due to its high prevalence and considerable contribution to the global disease burden. Recent studies suggest that genetic factors, including noncoding RNAs, have an important role in the progression of CVD. Noncoding RNA plays a critical role in genetic programming and gene regulation during development. Ferroptosis is a form of iron-dependent regulated cell death (RCD), which is mainly caused by increased lipid hydroperoxide and redox imbalance. Ferroptosis is essentially different from other forms of RCD in morphology and mechanism, such as apoptosis, autophagic cell death, pyroptosis, and necroptosis. Much evidence suggested ferroptosis is involved in the development of various CVDs, especially in cardiac ischemia/reperfusion injury, heart failure, and aortic dissection. Here, we review the latest findings based on noncoding RNA regulation of ferroptosis and its involvement in the pathogenesis of CVD and related treatments, aimed at providing insights into the impact of noncoding RNA regulation of ferroptosis for CVD.

Lipid peroxidation and lipid-soluble antioxidants as quality control markers in cold-stored fruit for establishing commercial acceptability in Bacon avocados

Avocados are prone to chilling injury disorders when stored at low temperatures. Although most studies have been performed in the worldwide distributed ‘Hass’ variety, other less exploited commercial varieties such as ‘Bacon’ might be more cold-tolerant. Aiming at evaluating how cold storage influences chilling injury, the extent of lipid peroxidation and the contents of lipophilic antioxidants were measured in ‘Bacon’ avocados. Harvested fruit were divided into two groups: one stored for 6 weeks at 4 °C and sampled at various time intervals for 42 days, and the other maintained at low temperatures for 3 and 6 weeks and then exposed to room temperature for 5 days until ripened. Long-term cold storage negatively influenced tocochromanols and carotenoids composition in unripen fruit, decreasing progressively both vitamin E and plastochromanol-8 contents, and most particularly carotenoids; yet chilling injury was prevented during cold storage for 6 weeks. When these fruits were ripened at room temperature, chilling injury increased 20% in the peel but only 5% in the mesocarp (edible part). Enhanced chilling injury in the mesocarp was associated with a 2.3-fold increase in lipid hydroperoxides (a primary lipid peroxidation product) and a 2.5-fold increase in plastochromanol-8 content, while contents of other tocochromanols, carotenoids and malondialdehyde (a secondary product of lipid peroxidation) kept unaltered. Interestingly, medium-term cold storage (3 weeks at 4 °C) did not lead to chilling injury in ripe fruit, therefore cold storage for 3 weeks is considered optimal to prevent large antioxidant vitamin degradation and maintain fruit quality in ripen avocados. In conclusion, despite the high cold tolerance shown by ‘Bacon’ avocados, fruit showed a strong depletion (60%) in carotenoids content after 6 weeks of storage at 4 °C, negatively affecting their commercial acceptability. Aside from evaluating visual chilling injury symptoms, evaluation of lipid peroxidation markers and contents of lipid-soluble antioxidants are deemed to be essential to establish commercial acceptability in cold-stored fruit.

Erythroid lineage Jak2V617F expression promotes atherosclerosis through erythrophagocytosis and macrophage ferroptosis.

Elevated hematocrit is associated with cardiovascular risk; however, the causality and mechanisms are unclear. The JAK2V617F (Jak2VF) mutation increases cardiovascular risk in myeloproliferative disorders and in clonal hematopoiesis. Jak2VF mice with elevated WBCs, platelets, and RBCs display accelerated atherosclerosis and macrophage erythrophagocytosis. To investigate whether selective erythroid Jak2VF expression promotes atherosclerosis, we developed hyperlipidemic erythropoietin receptor Cre mice that express Jak2VF in the erythroid lineage (VFEpoR mice). VFEpoR mice without elevated blood cell counts showed increased atherosclerotic plaque necrosis, erythrophagocytosis, and ferroptosis. Selective induction of erythrocytosis with low-dose erythropoietin further exacerbated atherosclerosis with prominent ferroptosis, lipid peroxidation, and endothelial damage. VFEpoR RBCs had reduced antioxidant defenses and increased lipid hydroperoxides. Phagocytosis of human or murine WT or JAK2VF RBCs by WT macrophages induced ferroptosis, which was prevented by the ferroptosis inhibitor liproxstatin-1. Liproxstatin-1 reversed increased atherosclerosis, lipid peroxidation, ferroptosis, and endothelial damage in VFEpoR mice and in Jak2VF chimeric mice simulating clonal hematopoiesis, but had no impact in controls. Erythroid lineage Jak2VF expression led to qualitative and quantitative defects in RBCs that exacerbated atherosclerosis. Phagocytosis of RBCs by plaque macrophages promoted ferroptosis, suggesting a therapeutic target for reducing RBC-mediated cardiovascular risk.

Protective effect of neurotensin receptor-1 agonist PD 149163 against lipopolysaccharide-induced gut toxicity in mice

The interaction between neuroendocrine and immune components of the gut maintains the organism's physical and psychological health. Its disruption may reflect in disease conditions such as inflammatory bowel disease (IBD) and mental illness. The lipopolysaccharide (LPS) disrupts the endocrine-immune homeostasis resulting in gut toxicity. The Neurotensin receptor-1 (NTR-1) agonist PD 149163 (PD) acts as an atypical antipsychotic drug in psychiatric illness, but its role in modulating gut pathophysiology remains unknown. Therefore, the aim of the present study was to evaluate the protective effect of PD against LPS-induced gut toxicity. Swiss albino female mice (12 weeks) were divided into six groups (n = 6/group): (I) Control, (II) LPS (1 mg/kg, for 5 days), (III) LPS (1 mg/kg, for 5 days)+PD low (100 µg/kg, for 21 days), (IV) LPS (1 mg/kg, for 5 days)+PD high (300 µg/kg, for 21 days), (V) PD low (100 µg/kg, for 21 days), and (VI) PD high (300 µg/kg, for 21 days). Drugs were given intraperitoneal in the morning. PD administration prevented the LPS-induced gut inflammation observed in damage of epithelial barrier, disruption of goblet cells, and condensation of lamina propria (LP). The LPS-induced oxidative stress characterized by decreased superoxide dismutase (SOD) activity and increased lipid hydroperoxide (LOOH) (p < 0.001 for both), and enhanced interleukine-6 (IL-6) & tumor necrosis factor-α (TNF-α) (p < 0.001 for both) as well as immunointensity of NT (p < 0.01) and NTR-1 (p < 0.05) were reversed and normalized to control after PD treatment. Thus, the anti-inflammatory, anti-oxidative, and cell proliferation properties of PD modulate the gut toxicity in LPS-challenged mice.

Vitamin D Supplementation Induces Cardiac Remodeling in Rats: Association with Thioredoxin-Interacting Protein and Thioredoxin.

ResumoFundamento:A vitamina D (VD) tem um importante papel na função cardíaca. No entanto, a vitamina exerce uma curva “dose-resposta” bifásica na fisiopatologia cardiovascular e pode causar efeitos deletérios, mesmo em doses não tóxicas. A VD exerce suas funções celulares ligando-se ao seu receptor. Ainda, a expressão da proteína de interação com a tiorredoxina (TXNIP) é positivamente regulada pela VD. A TXNIP modula diferentes visa de sinalização celular que podem ser importantes para a remodelação cardíaca.Objetivos:Avaliar se a suplementação com VD leva à remodelação cardíaca, e se a TXNIP e a tiorredoxina (Trx) estão associadas com esse processo.Métodos:Duzentos e cinquenta ratos Wistar machos foram alocados em três grupos: controle (C, n=21), sem suplementação com VD; VD3 (n = 22) e VD10 (n=21), suplementados com 3,000 e 10,000 UI de VD/ kg de ração, respectivamente, por dois meses. Os grupos foram comparados por análise de variância (ANOVA) com um fator e teste post hoc de Holm-Sidak (variáveis com distribuição normal), ou pelo teste de Kruskal-Wallis e análise post-hoc de Dunn. O nível de significância para todos os testes foi de 5%.Resultados:A expressão de TXNIP foi mais alta e a atividade do Trx foi mais baixa no grupo VD10. Os animais que receberam suplementação com VD apresentaram aumento de hidroperóxido lipídico e diminuição de superóxido dismutase e glutationa peroxidase. A proteína Bcl-2 foi mais baixa no grupo VD10. Observou-se uma diminuição na β-oxidação de ácidos graxos, no ciclo do ácido tricarboxílico, na cadeia transportadora de elétrons, e um aumento na via glicolítica.Conclusão:A suplementação com VD levou à remodelação cardíaca e esse processo pode ser modulado por TXNIP e Trx, e consequentemente por estresse oxidativo.

4-Octylphenol induces developmental abnormalities and interferes the differentiation of neural crest cells in Xenopus laevis embryos.

Developmental toxicity of 4-octylphenol (OP), an estrogenic endocrine disruptor was verified using frog embryo teratogenesis assay Xenopus. LC50, EC50Malformtion and EC50Melanocyte-dysgenesis of OP were 9.9, 10.5, and 2.4μM, respectively. In tadpoles, despite the low teratogenic index, 2μM OP significantly inhibited head cartilage development and tail malformation. The total length of tadpole was significantly increased at 5μM and decreased at 10μM OP. In OP-treated tadpoles, head cartilages were frequently missed and col2a1 mRNA was decreased at 2μM, indicating a chondrogenic defect in developing head. In the head skin of 1μM OP-treated tadpoles, number of melanocytes and melanogenic pathway genes expression were significantly decreased. In the head-neck junction of stage 22 embryos, OP increased foxd3 and sox10 mRNA and SOX10(+) neural crest cells (NCCs) in somite mesoderm and endoderm, indicating the inhibition of chondrogenic differentiation, ectopic migration to endoderm, and undifferentiation of NCCs by OP. Together, OP-induced head dysplasia and inhibition of melanogenesis may be attributable to deregulation of neural crest cells in embryos. In tadpoles, OP at 1μM significantly increased lipid hydroperoxide and induced spliced xbp1 mRNA, an IRE1 pathway endoplasmic reticulum stress (ERS) marker and p-eIF2α protein, a PERK pathway ERS marker. OP at 10μM induced CHOP mRNA, pro-apoptotic genes expression, DNA fragmentation, and cleaved caspase-3, suggesting that OP differentially induced ERS and apoptosis according to the concentration in embryos. In 5-10μM OP-treated stage 22 embryos and stage 45 tadpole heads, Ki67 was significantly increased, suggesting the apoptosis-induced proliferation of embryonic cells in the OP-treated embryos. Together, OP should be managed as a developmental toxicant altering the behavior of NCCs in vertebrates.

Effects of vitamin D administration on nociception and spinal cord pro-oxidant and antioxidant markers in a rat model of neuropathic pain.

Reactive oxygen species (ROS) are involved in neuropathic pain, a complicated condition after nerve tissue lesion. Vitamin D appears to improve symptoms of pain and exhibits antioxidant properties. We investigated the effects of oral administration of vitamin D3, the active form of vitamin D, on nociception, the sciatic functional index (SFI), and spinal cord pro-oxidant and antioxidant markers in rats with chronic constriction injury (CCI) of the sciatic nerve, a model of neuropathic pain. Vitamin D3 (500 IU/kg per day) attenuated the CCI-induced decrease in mechanical withdrawal threshold and thermal withdrawal latency (indicators of antinociception) and SFI. The vitamin prevented increased lipid hydroperoxide levels in injured sciatic nerve without change to total antioxidant capacity (TAC). Vitamin D3 prevented increased lipid hydroperoxide, superoxide anion generation (SAG), and hydrogen peroxide (H2O2) levels in the spinal cord, which were found in rats without treatment at 7 and 28 days post-CCI. A significant negative correlation was found between mechanical threshold and SAG and between mechanical threshold and H2O2 at day 7. Vitamin D3 also prevented decreased spinal cord total thiols content. There was an increase in TAC in the spinal cord of vitamin-treated CCI rats, compared to CCI rats without treatment only at 28 days. No significant changes were found in body weight and blood parameters of hepatic and renal function. These findings demonstrated, for first time, that vitamin D modulated pro-oxidant and antioxidant markers in the spinal cord. Since antinociception occurred in parallel with oxidative changes in the spinal cord, the oxidative changes may have contributed to vitamin D-induced antinociception.

Remote organs respond differently to curcumin treatment after intestinal ischemia/reperfusion injury

We aimed investigate the effects of 45 min of ischemia followed by 72 h of intestinal reperfusion (IR) in the ileum, liver, lungs, and kidneys in Wistar rats and the responses of these organs to curcumin treatment. Ischemia was induced by occluding the superior mesenteric artery. Rats were treated orally with 40 mg/kg curcumin. We analyzed oxidative stress and inflammation in the ileum, liver, lungs, and kidneys. Intestinal IR led to a reduction of reduced glutathione levels in the intestine, lungs, and kidneys and increased lipid hydroperoxide levels in all organs. An increase in the enzymatic activity of catalase was observed in all organs, and an increase in superoxide dismutase activity was observed in the ileum and lungs. Glutathione s-transferase levels increased only in the kidneys. Myeloperoxidase increased in all four organs, and n-acetyl-glycosaminidase increased only in the ileum and lungs. Curcumin prevented all of the changes in the ileum and liver. In the lungs, curcumin had no effect on n-acetyl-glycosaminidase. Curcumin did not prevent the changes in reduced glutathione, lipid hydroperoxides, or myeloperoxidase in the kidneys. Intestinal IR caused oxidative stress and inflammation in the ileum, lungs, and kidneys and to a lesser degree in the liver. Because of its systemic distribution, curcumin prevented changes mainly in the ileum, lungs, and liver and to a lesser degree in the kidneys.

Chronic khat (Catha edulis) chewing and genotoxicity: The role of antioxidant defense system and oxidative damage of DNA

Background: Khat chewing is culturally endemic in the Southern areas of Saudi Arabia. Many health-related issues such as the incidence of carcinogenicity and comorbidities associated with the chewing of khat have been reported earlier. Objectives: Mainly, the objective of the study was to assess the risk of genotoxicity caused due to oxidative stress that may result from khat chewing among chronic chewers from Jazan Province of Saudi Arabia. Materials and Methods: Hundred and twenty-two adult males were recruited after signing informed consent. Ninety participants were chronic khat chewers (CKCs), while the control group consisted of 32 non-chewers of matched age and gender for the study group. A blood sample was collected from all participants and kept at 4°C until the time of assay. The activity of superoxide dismutase (SOD) and glutathione reductase (GR) were estimated in erythrocyte lysate as well as 8-hydroxydeoxyguanosine (8-OHdG) level in plasma. Results: There is a decreased SOD activity, which might be due to an increase in the endogenous production of reactive oxygen species resulted from the increase in lipid hydroperoxides. Furthermore, the significant elevation in GR activity was observed, reflecting the presence of highly toxic compounds. The 8-OHdG levels were higher in khat chewers group in comparison to the control, but this increase was statistically insignificant. Conclusion: CKCs will be at considerable risk of oxidative stress as a result of a significant reduction in antioxidant enzymes. This would be a good reason for them to quit chewing khat for health benefits.

Isometric Exercise with Large Muscle Mass Improves Redox Balance and Blood Pressure in Hypertensive Adults.

The aim of this study was to investigate the hemodynamic, oxidative stress (OS), and nitric oxide (NO) responses to a submaximal isometric exercise session (IES) involving large muscle mass. Fourteen hypertensive (HTG: age = 35.9 ± 8.1 yr, height = 1.73 ± 0.10 m, total body mass = 78.0 ± 15.8 kg) and 10 normotensive (NTG: age = 41.1 ± 9.4 yr, height = 1.71 ± 0.12 m, total body mass = 82.3 ± 22.4 kg) participants performed two experimental sessions in the leg press and bench press: (i) control session and (ii) 8 sets × 1 min contraction at 30% maximal voluntary isometric contraction with 2-min rest interval. Blood pressure (BP) was measured at rest and during 60 min postexercise. Blood samples were collected at rest, immediately after the session, and 60 min postexercise. NO was obtained through the Griess reaction method. OS parameters were analyzed using commercial kits. A repeated-measures ANOVA with Bonferroni post hoc test was used to analyze all dependent variables. A significant decrease in systolic BP was observed only for HTG at 45 and 60 min postexercise (baseline vs 45 min: P = 0.03, Δ% = 4.44%; vs 60 min: P = 0.018, Δ% = 5.58%). NO increased immediately postexercise only for HTG (P = 0.008, Δ% = 16.44%). Regarding OS parameters, thiobarbituric acid reactive substances presented a significant reduction 60 min after the IES for NTG and HTG; catalase increased in both groups. The data showed that only 8 min of IES with a large muscle mass elicits an elevated pro-oxidant activity leading to a greater NO bioavailability, increases antioxidant reaction, and consequently reduces BP in hypertensive patients.

Brain-Derived Neurotrophic Factor and Oxidative Stress in Cannabis Dependence

Introduction: Neurotrophin levels and oxidative stress markers such as ceruloplasmin and free thiols have been shown to contribute to pathophysiology in several psychiatric disorders. Objective: Our aim is to evaluate whether those markers are altered in cannabis dependence. Methods: Forty-five cannabis-dependent patients diagnosed according to the DSM-IV criteria and 45 healthy controls matched according to sex, age, BMI, and smoking status were enrolled. Brain-derived neurotrophic factor (BDNF), ceruloplasmin, lipid hydroperoxide, and total free thiols were measured in both groups. Those who had psychiatric comorbidities were excluded before sampling. Results: We found significantly increased BDNF, ceruloplasmin, and lipid hydroperoxide, and decreased free thiol levels in patients with cannabis dependence. There is also a positive correlation between BDNF and lipid hydroperoxide (n = r = 0.472, p < 0.001) and a negative correlation between BDNF and total thiols (n = r = –0.412, p = 0.001). Conclusions: Increased BDNF might be a sign of impaired neuronal plasticity that is crucial for memory formation and adaptive response to drug addiction. Neuronal plasticity in the ventral tegmental area dopaminergic neurons was implied to play a role in substance addiction disorders, and these adaptations can be secondary to oxidative stress. Our findings, including increased lipid hydroperoxide, ceruloplasmin, and decreased free thiols, might support this hypothesis. In conclusion, cannabis dependency alters BDNF levels and increases oxidative stress.

Copper nanoparticles modify the blood plasma antioxidant status and modulate the vascular mechanisms with nitric oxide and prostanoids involved in Wistar rats.

We aimed to analyze whether a diet supplemented with a standard dose of copper (Cu) in the form of nanoparticles, as an alternative to carbonate, exerts beneficial effects within the vasculature and improves the blood antioxidant status. Male Wistar rats were fed for 8 weeks with a diet supplemented with Cu (6.5 mg Cu/kg in the diet) either as nanoparticles (40 nm diameter) or carbonate - the control group. Moreover, a negative control was not supplemented with Cu. At 12 weeks of age, blood samples, internal organs and thoracic aorta were taken for further analysis. Blood antioxidant mechanism was measured together with Cu and Zn. Diet with Cu as nanoparticles resulted in an elevated catalase activity and ferric reducing ability of plasma, however decreased Cu (plasma), and ceruloplasmin (Cp) compared to carbonate. The participation of vasoconstrictor prostanoid was increased, as indomethacin did not modify the acetylcholine (ACh)-induced response. Arteries from Cu nanoparticle and carbonate rats exhibited a reduced maximal contraction to potassium chloride and an increased response to noradrenaline. The endothelium-dependent vasodilation to ACh was enhanced while exogenous NO donor, sodium nitroprusside, did not modify the vascular response. Down-regulation of BKCa channels influenced hyperpolarizing mechanism. The superoxide dismutase and HDL-cholesterol were decreased opposite to an increased lipid hydroperoxides, malondialdehyde, Cu (plasma and liver) and Cp. Despite the increased antioxidant capacity in blood of Cu nanoparticle fed rats, vasoconstrictor prostanoids and NO are involved in vascular regulation.

Effect of reduced glutathione on the indexes of oxidative stress and heme metabolism in liver and blood of rats under hemin chloride injection in vivo

Heme (iron-protoporphyrin IX) is involved in various cellular functions. The release of heme under hemolysis or under the damage of intracellular hemeproteins leads to its accumulation in tissues and, as a result, to the activation of free radical processes. Reduced glutathione (GSH) functions as an endogenous water-soluble antioxidant and a regulator of cells redox status, but its effect on the development of oxidative stress under hemin action in mammals remains not investigated. The aim of this work was to study the effect of hemin chloride on some hemeproteins activity and a number of prooxidant-antioxidant status indexes in rat liver and blood under GSH level modulation in vivo. White male rats weighing 170–280 g were taken for investigation. Hemin chloride and GSH were injected intraperitoneally. Blood plasma, homogenate, and postmitochondrial fraction of liver were the objects of study. Hemin chloride injection (50 mg/kg body weight) caused the increase in heme-containing products level in blood and free heme level in liver of rats, which was accompanied by the activation of free radical processes in these tissues. The accumulation of free heme in liver was proved by an increase in tryptophan 2,3-dioxygenase (TDO) holoenzyme activity and heme saturation. The pretreatment by GSH (500 mg/kg body weight) 0.5 h before hemin chloride injection normalized GSH content, but did not prevent heme accumulation, the decrease in triglycerides level and the increase in lipid hydroperoxides content in rat blood plasma under hemin action. In liver, GSH injection prevented the increase in lipid hydroperoxides and protein carbonyl derivatives concentration as well as in TDO holoenzyme activity, and decreased the degree of TDO heme saturation. All these changes occurred under GSH content increase in liver. Catalase activity in liver did not differ from the control values after hemin chloride injection as well as after glutathione and hemin coadministration. The analysis of relationship between parameters studied in this work revealed the strong positive correlation between GSH content in plasma and liver (r=0.85; p&lt;0.001), which was consistent with literature data on the significant role of liver in supplying other tissues with reduced glutathione. A negative correlation was found between lipid peroxidation products and triglycerides content in plasma (r=–0.52; p&lt;0.05), which indicated the participation of triglycerides unsaturated fatty acids as substrates in the peroxidation processes under hemin action. No significant correlation between GSH and hydroperoxides content, as well as between GSH and heme-containing products levels in blood plasma was revealed. Thus, the water-soluble antioxidant glutathione was not effective enough to prevent damage of lipid components in blood under hemin chloride action in the selected dose. In the liver, on the contrary, GSH injection prevented heme accumulation and oxidative stress development under hemin action, which was obviously associated with an increase in the GSH content in this organ.