Possible role of pomegranate fruit in reversing renal damage in rats exposed to Phenylhydrazine.

Background: Pomegranate granatum (molasses and peels) and its constituents showed protective effects against natural toxins such as phenylhydrazine (PHZ) as well as chemical toxicants such as arsenic, diazinon, and carbon tetrachloride. Aim: The current study aimed to assess the effect of pomegranate molasses (PM), white peel extract, and red peel extract on nephrotoxicity induced by PHZ. Methods: 80 male rats were divided into eight equal groups; a control group, PM pure group, white peel pomegranate pure group, red peel pomegranate pure group, PHZ group, PM + PHZ group, white peel pomegranate + PHZ group and red peel pomegranate + PHZ group. Kidney function, inflammation markers, antioxidant activities, and renal tissue histopathology were investigated. Results: The results revealed that PHZ group showed a significant increase in lactate Dehydrogenase (LDH), malondialdehyde (MDA), creatinine, uric acid, BUNBUN, C - reactive protein (CRP), tumor necrosis factor, thiobarbituric acid reactive substances (TBARSs), and total antioxidant capacity (TAC) with a significant decrease of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) as compared with a control group. Other pomegranate-treated and PHZ co-treated groups with pomegranate showed a significant decrease of LDH, MDA, creatinine, uric acid, BUN, tumor necrosis factor, TBARSs, and TAC with a significant increase of CAT, GPx, and SOD as compared with PHZ group. Conclusion: Collectively, our data suggest that red, white peels, and molasses have anti-toxic and anti-inflammatory effects on renal function and tissues.

Oxidative stress-related biomarkers in chronic periodontitis patients with or without type 2 diabetes: A systematic review and meta-analysis.

OBJECTIVE: The purpose of this meta-analysis was to look at the differences in oxidative stress (OS) biomarkers between type 2 diabetes mellitus with chronic periodontitis (DMCP) and chronic periodontitis (CP) patients. BACKGROUND: Oxidative stress has been shown to be a key pathogenic component in DMCP. However, it is unclear whether oxidative stress levels differ in periodontitis patients with or without diabetes. METHOD: A systematic search was conducted on PubMed, Cochrane, and Embase databases. Studies of DMCP participants were used as the experimental group and CP participants were used as the control group. Results are expressed as mean effects. RESULTS: Of a total of 1989 articles, 19 met the inclusion criteria. We found the levels of catalase (CAT) levels were reduced in the DMCP group compared with the CP group. However, there was no significant difference in the levels of superoxide dismutase (SOD), total antioxidant capacity (TAOC) malondialdehyde (MDA), and glutathione (GSH) between the two groups. And high heterogeneity was observed in some of the studies evaluated. CONCLUSION: Despite the limitations of this study, our results support the theory that there is an association between T2DM and the levels of OS-related biomarkers, especially CAT, in CP subjects, suggesting that OS plays an important role in the pathogenesis and development of DMCP.

Green coffee bean extract attenuates gentamicin induced acute nephrotoxicity in rats / El extracto de grano de café verde atenúa la nefrotoxicidad aguda inducida por gentamicina en ratas

Gentamicin induced acute nephrotoxicity (GIAN) is considered as one of the important causes of acute renal failure. In recent years' great effort has been focused on the introduction of herbal medicine as a novel therapeutic agent for prevention of GIAN. Hence, the current study was designed to investigate the effect of green coffee bean extract (GCBE) on GIAN in rats. Results of the present study showed that rat groups that received oral GCBE for 7 days after induction of GIAN(by a daily intraperitoneal injection of gentamicin for 7days), reported a significant improvement in renal functions tests when compared to the GIAN model groups. Moreover, there was significant amelioration in renal oxidative stress markers (renal malondialdehyde, renal superoxide dismutase) and renal histopathological changes in the GCBE-treated groups when compared to GIAN model group. These results indicate that GCBE has a potential role in ameliorating renal damage involved in GIAN.

La nefrotoxicidad aguda inducida por gentamicina (GIAN) se considera una de las causas importantes de insuficiencia renal aguda. En los últimos años, el gran esfuerzo se ha centrado en la introducción de la medicina herbal como un nuevo agente terapéutico para la prevención de GIAN. Por lo tanto, el estudio actual fue diseñado para investigar el efecto del extracto de grano de café verde (GCBE) sobre la GIAN en ratas. Los resultados del presente estudio mostraron que los grupos de ratas que recibieron GCBE oral durante 7 días después de la inducción de GIAN (mediante una inyección intraperitoneal diaria de gentamicina durante 7 días), informaron una mejora significativa en las pruebas de función renal en comparación con los grupos del modelo GIAN. Además, hubo una mejora significativa en los marcadores de estrés oxidativo renal (malondialdehído renal, superóxido dismutasa renal) y cambios histopatológicos renales en los grupos tratados con GCBE en comparación con el grupo del modelo GIAN. Estos resultados indican que GCBE tiene un papel potencial en la mejora del daño renal involucrado en GIAN.

SOD2, a Potential Transcriptional Target Underpinning CD44-Promoted Breast Cancer Progression.

CD44, a cell-adhesion molecule has a dual role in tumor growth and progression; it acts as a tumor suppressor as well as a tumor promoter. In our previous work, we developed a tetracycline-off regulated expression of CD44's gene in the breast cancer (BC) cell line MCF-7 (B5 clone). Using cDNA oligo gene expression microarray, we identified SOD2 (superoxide dismutase 2) as a potential CD44-downstream transcriptional target involved in BC metastasis. SOD2 gene belongs to the family of iron/manganese superoxide dismutase family and encodes a mitochondrial protein. SOD2 plays a role in cell proliferation and cell invasion via activation of different signaling pathways regulating angiogenic abilities of breast tumor cells. This review will focus on the findings supporting the underlying mechanisms associated with the oncogenic potential of SOD2 in the onset and progression of cancer, especially in BC and the potential clinical relevance of its various inhibitors.

A study on the antioxidant activity of rosmarinic acid against carbon tetrachloride-induced liver toxicity in adult male albino rats / Estudio sobre la actividad antioxidante del ácido rosmarínico contra la toxicidad hepática inducida por tetracloruro de carbono en ratas albinas macho adultas

SUMMARY: Carbon tetrachloride (CCl4) is a manufactured chemical and does not occur naturally in the environment. CCl4 is a clear liquid that evaporates very easily. It has a sweet odor. CCl4 is toxic to the mammalian liver and is hepatocarcinogenic in both rats and mice. Rosemary (Rosmarinus Officinalis) is commonly used as a spice and flavoring agent in food processing. It is known for its antioxidant properties. The present study aims to investigate the antioxidant activity of rosmarinic acid (RA) on CCl4-induced liver toxicity in adult male albino rats. Forty adult male albino rats were divided into 4 groups with 10 rats in each group. Group I (control group). Group II animals received RA at a dose of 50 mg/kg/day by oral gavage for 4 weeks. Group III animals received CCl4 intraperitoneally at a dose of 3ml/kg twice weekly for 4 weeks. Group IV animals received CCl4 Plus RA. At the end of the experiment, liver specimens are processed for histological, immunohistochemical, EM and biochemical studies. Administration of RA deceased the elevated serum liver enzymes (AST, ALT, and ALP), elevated MDA level and immunoexpression of the proapoptotic protein (Bax) induced by CCl4. It increased reduced glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and immunoexpression of the antiapoptotic protein (Bcl2). It also improved the histological and ultrastructural changes induced by CCl4. It appears that Rosmarinic acid has protective effects against CCl4-induced hepatotoxicity as indicated by biochemical, histological, immunohistochemical and ultrastructural results.

RESUMEN: El tetracloruro de carbono (CCl4) es un producto químico fabricado y no se encuentra de forma natural en el medio ambiente. CCl4 es un líquido transparente que se evapora fácilmente; tiene un olor dulce. CCl4 es tóxico para el hígado de los mamíferos y es hepatocarcinogénico tanto en ratas como en ratones. El romero (Rosmarinus officinalis) se usa comúnmente como condimento y agente aromatizante en el procesamiento de alimentos. Es conocido por sus propiedades antioxidantes. El presente estudio tuvo como objetivo investigar la actividad antioxidante del ácido rosmarínico (RA) sobre la toxicidad hepática inducida por CCl4 en ratas albinas macho adultas. Se dividieron cuarenta ratas albinas macho adultas en 4 grupos con 10 ratas en cada grupo. Grupo I (grupo control). Los animales del grupo II recibieron AR a una dosis de 50 mg / kg / día por sonda oral durante 4 semanas. Los animales del grupo III recibieron CCl4 por vía intraperitoneal a una dosis de 3 ml / kg dos veces por semana durante 4 semanas. Los animales del grupo IV recibieron CCl4 Plus RA. Al final del experimento, las muestras de hígado se procesaron para estudios histológicos, inmunohistoquímicos, EM y bioquímicos. La administración de AR eliminó las enzimas hepáticas séricas elevadas (AST, ALT y ALP), el nivel elevado de MDA y la inmunoexpresión de la proteína proapoptótica (Bax) inducida por CCl4. Aumentó el glutatión reducido (GSH), glutatión peroxidasa (GSH-Px), la superóxido dismutasa (SOD) y la inmunoexpresión de la proteína antiapoptótica (Bcl2). También mejoró los cambios histológicos y ultraestructurales inducidos por CCl4. El ácido rosmarínico puede tener efectos protectores contra la hepatotoxicidad inducida por CCl4, tal como lo indican los resultados bioquímicos, histológicos, inmunohistoquímicos y ultraestructurales.

The Ameliorative Effects of Saikosaponin in Thioacetamide-Induced Liver Injury and Non-Alcoholic Fatty Liver Disease in Mice.

Liver disorders are a major health concern. Saikosaponin-d (SSd) is an effective active ingredient extracted from Bupleurum falcatum, a traditional Chinese medicinal plant, with anti-inflammatory and antioxidant properties. However, its hepatoprotective properties and underlying mechanisms are unknown. We investigated the effects and underlying mechanisms of SSd treatment for thioacetamide (TAA)-induced liver injury and high-fat-diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in male C57BL/6 mice. The SSd group showed significantly higher food intake, body weight, and hepatic antioxidative enzymes (catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD)) and lower hepatic cyclooxygenase-2 (COX-2), serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, and fibroblast growth factor-21 (FGF21) compared with controls, as well as reduced expression of inflammation-related genes (nuclear factor kappa B (NF-κB) and inducible nitric oxide synthase (iNOS)) messenger RNA (mRNA). In NAFLD mice, SSd reduced serum ALT, AST, triglycerides, fatty acid-binding protein 4 (FABP4) and sterol regulatory element-binding protein 1 (SREBP1) mRNA, and endoplasmic reticulum (ER)-stress-related proteins (phosphorylated eukaryotic initiation factor 2α subunit (p-eIF2α), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP). SSd has a hepatoprotective effect in liver injury by suppressing inflammatory responses and acting as an antioxidant.

Effects of hyperbaric oxygen pretreatment on brain antioxidant capacity in rats with decompression sickness.

OBJECTIVE: Decompression sickness (DCS) causes serious brain hypoxic-ischemic injury. This experiment was designed to observe whether hyperbaric oxygen (HBO2) pretreatment played a neuroprotective effect in decompression sickness rat models and to explore the mechanism of protective effects. METHODS: Sprague-Dawley (SD) male rats were pretreated with HBO2 and then underwent decompression to establish the DCS rat model. Antioxidant capacities were evaluated by detecting peroxides (GPx), superoxide dismutase (SOD), catalase (CAT) activity and malondialdehyde (MDA) content in brains. The levels of metal elements manganese (Mn), zinc (Zn), iron (Fe) and magnesium (Mg) in brain tissues were assessed by flame atomic absorption spectrometry. Necrosis and apoptosis of neurons were assessed by H-E staining and immunohistochemical staining. RESULTS: HBO2 pretreatment reduced the degree of necrosis and apoptosis in brain tissues of decompression sickness rat models. In addition, HBO2 pretreatment increased GPx, SOD and CAT activities and reduced MDA accumulation. It also increased the content of Mn, Zn, Fe and Mg in brain tissue, which are all related to free radical metabolism. CONCLUSION: These results suggested that HBO2 pretreatment has protective effects on brain injury of rats with decompression sickness. The mechanism of the protective effects may be related to reducing oxidative damage by affecting metal elements in vivo.

Activity of CdTe Quantum-Dot-Tagged Superoxide Dismutase and Its Analysis in Capillary Electrophoresis.

Quantum dots (QDs) have a broad range of applications in cell biolabeling, cancer treatment, metastasis imaging, and therapeutic drug monitoring. Despite their wide use, relatively little is known about their influence on other molecules. Interactions between QDs and proteins can influence the properties of both nanoparticles and proteins. The effect of mercaptosuccinic acid-capped CdTe QDs on intercellular copper-zinc superoxide dismutase (SOD1)-one of the main enzymatic antioxidants-was investigated. Incubation of SOD1 with QDs caused an increase in SOD1 activity, unlike in the case of CdCl2, which inhibited SOD1. Moreover, this effect on SOD1 increased with the size and potential of QDs, although the effect became clearly visible in higher concentrations of QDs. The intensity of QD-SOD1 fluorescence, analyzed with the use of capillary electrophoresis with laser-induced fluorescence detection, was dependent on SOD1 concentration. In the case of green QDs, the fluorescence signal decreased with increasing SOD1 concentration. In contrast, the signal strength for Y-QD complexes was not dependent on SOD1 dilutions. The migration time of QDs and their complexes with SOD1 varied depending on the type of QD used. The migration time of G-QD complexes with SOD1 differed slightly. However, in the case of Y-QD complexes with SOD1, the differences in the migration time were not dependent on SOD concentration. This research shows that QDs interact with SOD1 and the influence of QDs on SOD activity is size-dependent. With this knowledge, one might be able to control the activation/inhibition of specific enzymes, such as SOD1.

Walking Training Improves Systemic and Local Pathophysiological Processes in Intermittent Claudication.

OBJECTIVE: This study examined the impact of submaximal walking training (WT) on local and systemic nitric oxide (NO) bioavailability, inflammation, and oxidative stress in patients with intermittent claudication (IC). METHODS: The study employed a randomised, controlled, parallel group design and was performed in a single centre. Thirty-two men with IC were randomly allocated to two groups: WT (n = 16, two sessions/week, 15 cycles of two minutes walking at an intensity corresponding to the heart rate obtained at the pain threshold interspersed by two minutes of upright rest) and control (CO, n = 16, two sessions/week, 30 minutes of stretching). NO bioavailability (blood NO and muscle nitric oxide synthase [eNOS]), redox homeostasis (catalase [CAT], superoxide dismutase [SOD], lipid peroxidation [LPO] measured in blood and muscle), and inflammation (interleukin-6 [IL-6], C-reactive protein [CRP], tumour necrosis factor α [TNF-α], intercellular adhesion molecules [ICAM], vascular adhesion molecules [VCAM] measured in blood and muscle) were assessed at baseline and after 12 weeks. RESULTS: WT statistically significantly increased blood NO, muscle eNOS, blood SOD and CAT, and muscle SOD and abolished the increase in circulating and muscle LPO observed in the CO group. WT decreased blood CRP, ICAM, and VCAM and muscle IL-6 and CRP and eliminated the increase in blood TNF-α and muscle TNF-α, ICAM and VCAM observed in the CO group. CONCLUSION: WT at an intensity of pain threshold improved NO bioavailability and decreased systemic and local oxidative stress and inflammation in patients with IC. The proposed WT protocol provides physiological adaptations that may contribute to cardiovascular health in these patients.

In vivo toxicity and antioxidant of pressurize hot water Phyllanthus tenellus Roxb. extracts.

BACKGROUND: Phyllanthus tenellus Roxb. has been traditionally used to treat inflammation and liver diseases and its medicinal property may be due to the presence of relatively high levels of hydrosable tannins. Recent report revealed that pressurized hot water extraction of P. tenellus significantly increased the concentration of hydrolysable tannins and its catabolites. Thus, this study was aimed to evaluate the in vivo toxicity and antioxidant capacity of pressurized hot water extraction of P. tenellus on healthy mice. METHODS: Pressurized hot water extraction P. tenellus was carried out and standardized to 7.9% hydrosable tannins. In vitro toxicity of the extract was tested on NIH 3 T3 cell by MTT assay. The cellular antioxidant level was quantified by measuring cellular level of glutathione. Oral sub-chronic toxicity (200, 1000 and 3000 mg/kg body weight) of P. tenellus extract were evaluated on healthy mice. Liver and kidney antioxidant level was quantified by measuring levels of Ferric Reducing Antioxidant Potential (FRAP), superoxide dismutase, glutathione. RESULTS: The P. tenellus extract did not induce cytotoxicity on murine NIH 3 T3 cells up to 200 µg/mL for 48 h. Besides, level of glutathione was higher in the extract treated NIH 3 T3 cells. P. tenellus extract did not cause mortality at all tested concentration. When treated with 1000 mg/kg of the extract, serum liver enzymes (ALP and ALT) and LDH were lower than normal control and mice treated with 200 mg/kg of extract. Moreover, SOD, FRAP and glutathione levels of liver of the mice treated with 200 and 1000 mg/kg of extract were higher than the normal control mice. On the other hand, when treated with 3000 mg/kg of extract, serum liver enzymes (ALP and ALT) and LDH were higher than normal mice without changing the liver SOD and glutathione level, which may contribute to the histological sign of ballooning hepatocyte. CONCLUSION: P. tenellus extract standardized with 7.9% hydrosable tannins and their catabolites increased the antioxidant levels while reducing the nitric oxide levels in both liver and kidney without causing any acute and sub-chronic toxicity in the mice.

Correlations of Silent Information Regulator of Transcription 1 (SIRT1) Expression, Inflammatory Factors, and Oxidative Stress with Pulmonary Function in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD).

BACKGROUND The aim of this study was to investigate the correlations of silent information regulator of transcription 1 (SIRT1) expression, inflammatory factors, and oxidative stress with pulmonary function in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). MATERIAL AND METHODS Bronchoalveolar lavage fluid (BALF) was collected from 188 patients with COPD (83 in stable phase and 105 in acute exacerbation phase) and 56 healthy controls. Subsequently, the SIRT1 expression levels, the IL-6 and IL-8 levels (the representatives of inflammatory factors), and the MDA and SOD levels (indicative of oxidative stress) were detected via enzyme-linked immunosorbent assay. Correlations of SIRT1 expression, inflammatory factors, and oxidative stress with pulmonary function parameters [forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) and FEV1] were measured via Spearman's correlation analysis. RESULTS The levels of inflammatory factors and oxidative stress were elevated and SIRT1 expression remarkably declined in patients with AECOPD compared with those in healthy controls and stable COPD patients (P<0.05). Spearman's correlation analysis revealed that SIRT1 expression, interleukin (IL)-6, and IL-8 were strongly associated with pulmonary function parameters (FEV1/FVC and FEV1) in patients with AECOPD (P<0.001), while no such obvious correlation was observed in stable COPD patients. CONCLUSIONS Oxidative stress and expression levels of inflammatory factors are evidently elevated and SIRT1 expression declines in patients with AECOPD. Moreover, SIRT1 expression is positively associated with pulmonary function parameters, while IL-6 and IL-8 exhibit negative correlations with pulmonary function parameters.

Calm Hu ram lambs assigned by temperament classification are healthier and have better meat quality than nervous Hu ram lambs.

The objective of this study was to evaluate the effects of temperament classification (assessed using an arena test) on health and productivity of Hu ram lambs. In experiment one, eight ram lambs classified as calm and eight classified as nervous (selected from 100 ram lambs) were fed individually for 60-days to compare food intake, food digestibility, weight gain, and biochemical indices of health. In experiment two, nine ram lambs classified as calm and nine classified as nervous (selected from 150 ram lambs) were fed in a group and slaughter traits, meat quality, and muscle histology were compared. Calm lambs had higher dry matter digestibility, lower serum TNF-α, higher total antioxidant capacity, higher total superoxide dismutase activity, higher dressing percentage, higher cross-sectional area of loin, higher myofibre density, lower ultimate pH of the meat, and higher meat redness, than nervous lambs. Selection for calm temperament could be beneficial to health, slaughter, and carcass traits in Hu ram lambs.

Relationship between nuclear DNA fragmentation, mitochondrial DNA damage and standard sperm parameters in spermatozoa of infertile patients with leukocytospermia.

The association of leukocytospermia with male fertility is still under debate. Our objective was to evaluate the association of leukocytospermia with sperm parameters, mitochondrial DNA (mtDNA) variations, and seminal concentration of several oxidative stress and inflammatory cytokines in Tunisian infertile men. The studied patients were divided into two groups: patients without leukocytospermia (Group 1) and patients with leukocytospermia (Group 2). DNA fragmentation significantly increased in group 2 (31.41 %) compared to group 1 (14.68 %) ; (p < 0.001). A total of 115 nucleotide substitutions in mitochondrial DNA were depicted, among which 113 were previously identified. The number of substitutions was more elevated in group 2. Leukocytospermic group had significantly higher MDA (nmole/mL) levels than patients without leukocytospermia (34±24.43 vs 18.94±15.96 ; p=0.001), GSH (µg/mL) levels were also higher compared to the control group (126.53±22.87 vs 79.4±19.38 ; p < 0.001), SOD (U/mg of protein) levels were higher but without reaching the statistical significance (89.74±74.85 vs 67.56±37.11 ; p = 0.25) ; whereas seminal CAT (µmole H2O2/min/mg of protein) levels were lower in this group (10.66±14.32 vs 27.35±25.28 ; p = 0.012). No statistically significant differences between the two groups of patients were found in the levels of inflammatory cytokines. However, IL-8 level was positively correlated with DNA fragmentation and negatively correlated with vitality. These findings confirm the association between leukocytospermia and sperm DNA damage.

The effect of hormonal levels and oxidative stress on bisphenol A and soy isoflavone reproductive toxicity in murine offspring.

Previous studies have suggested that human exposure to bisphenol A (BPA) and soy isoflavones (SIFs) can occur during pregnancy. The combination of these chemicals is hypothesized to have a toxic impact on the fetus. While BPA is an industrial chemical used widely in the manufacture of polycarbonate plastics and epoxy resins, SIFs are naturally occurring estrogen­like phytoestrogens. To determine the impact of the combination of BPA and SIFs on fetal development, the body weight, organ weight, anogenital distance and histopathological changes in the testes of F1 offspring were assessed in mice. Hormonal effects were determined by measuring serum levels of estrogen receptor (ESR), follicle­stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T). Additionally, mitochondrial DNA copy numbers, and the serum levels of malondialdehyde and superoxide dismutase, were determined to evaluate alterations in oxidative stress and potential toxicity. Exposure to BPA increased the body weight of the pups and reduced the ratio of anogenital distance to body weight, as well as testes weight. Moreover, BPA exposure also induced testicular lesions. The seminiferous tubules of testis were denatured in varying degrees and the lumen wall structure was disordered. The levels of ESR in all offspring and the T levels in male offspring significantly increased, compared with controls. Co­exposure to BPA and SIFs exacerbated these changes in body weight, testicular lesions and hormonal levels, relative to BPA exposure alone. Additionally, oxidative damage was only induced by high­dose BPA. Collectively, these findings suggested that BPA and SIFs could have synergistic effect on the reproductive system, which could be mediated by the regulation of ESR expression and testosterone release.

Changes in Glutathione, Ascorbate, and Antioxidant Enzymes during Olive Fruit Ripening.

The content of glutathione, ascorbate (ASC), and the enzymatic antioxidants, superoxide dismutase and catalase, and components of the ascorbate-glutathione cycle were investigated in the olive fruit (cv. Picual) selected at the green, turning, and mature ripening stages. The changes observed in total and reduced glutathione (GSH), oxidized glutathione (GSSG), the ratio GSH/GSSG, ASC, and antioxidant enzymes (mainly superoxide dismutase, catalase, ascorbate peroxidase, and glutathione reductase) indicate a shift to a moderate cellular oxidative status during ripening and suggest a role for antioxidants in the process. The antioxidant composition of olive oils obtained from the olive fruits of the study was investigated. A model is proposed for the recycling of antioxidant polyphenols mediated by endogenous molecular antioxidants in the olive fruit.

Induction of brain injury and depression in rats by chronic unpredictable stress associated with the augmentation of nitrosative stress and apoptosis / Inducción de lesión cerebral y depresión en ratas por estrés crónico impredecible asociado con el aumento del estrés nitrosativo y la apoptosis

SUMMARY: Repeated stress is a risk factor for memory impairment and neurological abnormalities in both humans and animals. We sought to investigate the extent of (i) brain tissue injury; (ii) nitrosative and oxidative stress in brain tissue homogenates; (iii) apoptotic and survival biomarkers in brain tissue homogenates; and (iv) immobility and climbing abilities, induced over a period of three weeks by chronic unpredictable stress (CUS). Wistar rats were either left untreated (Control group) or exposed to a variety of unpredictable stressors daily before being sacrificed after 3 weeks (model group). Assessment of depression-like behavior was performed and animals were then culled and harvested brain tissues were stained with basic histological staining and examined under light microscopy. In addition, brain tissue homogenates were prepared and assayed for these parameters; inducible nitric oxide synthase (iNOS), malondialdehyde (MDA), superoxide dismutase (SOD), caspase-3, and B-cell lymphoma 2 (Bcl-2). Histology images showed CUS induced profound damage to the cerebral cortex as demonstrated by severe neuronal damage with shrunken cells, disrupted atrophic nuclei, perineuronal vacuolation and swollen glial cells. CUS also significantly (p<0.05) induced iNOS, MDA, and caspase-3, whereas SOD and Bcl-2 brain tissue levels were inhibited by CUS. In addition, data from the depression-like behavior, forced swimming test showed significant (p<0.05) increase in animal immobility and decrease in climbing ability in the model group of rats. Thus, here we demonstrated a reliable rat model of chronic stress-induced brain injury, which can further be used to investigate beneficial drugs or agents used for a period of three weeks to protect against CUS-induced brain damage.

RESUMEN: El estrés crónico es un factor de riesgo para el deterioro de la memoria y las anomalías neurológicas tanto en humanos como en animales. Intentamos investigar el alcance de lesión del tejido cerebral; (ii) estrés nitrosativo y oxidativo en homogeneizados de tejido cerebral; (iii) biomarcadores apoptóticos y de supervivencia en homogeneizados de tejido cerebral; y (iv) inmovilidad y habilidades de escalada, inducidas durante un período de tres semanas por estrés crónico impredecible (ECI). Se dejaron sin tratamiento (grupo control) ratas Wistar, o se expusieron a una variedad de factores estresantes impredecibles diariamente antes de ser sacrificadas después de 3 semanas (grupo modelo). Se realizó una evaluación del comportamiento similar a la depresión y luego se sacrificaron los animales y se tiñeron los tejidos cerebrales con tinción histológica básica y se examinaron con microscopía óptica. Además, se prepararon homogeneizados de tejido cerebral y se analizaron los siguientes parámetros; óxido nítrico sintasa inducible (iNOS), malondialdehído (MDA), superóxido dismutasa (SOD), caspasa- 3 y linfoma de células B 2 (Bcl-2). Las imágenes histológicas mostraron que el CUS indujo un daño profundo en la corteza cerebral como lo demuestra el daño neuronal severo con células encogidas, núcleos atróficos alterados, vacuolación perineuronal y células gliales inflamadas. ECI también indujo significativamente (p <0,05) iNOS, MDA y caspase-3, mientras que los niveles de tejido cerebral SOD y Bcl-2 fueron inhibidos por ECI. Además, los datos del comportamiento similar a la de- presión, la prueba de natación forzada mostró un aumento significativo (p <0,05) en la inmovilidad animal y una disminución en la capacidad de escalada en el grupo modelo de ratas. Por lo tanto, aquí demostramos un modelo confiable de daño cerebral crónico en rata inducido por el estrés, que se puede utilizar para investigar medicamentos o agentes beneficiosos usados durante un período de tres semanas para proteger el daño cerebral inducido por ECI.

Effect of Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes), Capsules on Colistin-Induced Nephrotoxicity.

The aim of this experimental study was to investigate the protective effect of Ganoderma lucidum capsules against colistin nephrotoxicity. The study animals were separated into four groups: control, colistin (9 mg/kg), colistin-G. lucidum 50 mg/kg, and colistin-G. lucidum 100 mg/kg. In the colistin group, serum blood urea nitrogen and creatinine values were found to be higher than those of the other groups (p < 0.001). The malondialdehyde, catalase, total oxidative stress, oxidative stress index, and oxidized glutathione values in serum and kidney tissue samples were determined to be higher in the colistin group than in the other groups (p < 0.001). The total antioxidative stress, superoxide dismutase, glutathione peroxidase, and glutathione values measured in the serum and kidney tissue samples were determined to be lower in the colistin group (p < 0.001). Oxidative stress is responsible for tubule damage in colistin nephrotoxicity, and when G. lucidum is used together with colistin, renal damage is reduced.

An in vitro study to assess the effect of hyaluronan-based gels on muscle-derived cells: Highlighting a new perspective in regenerative medicine.

Hyaluronan (HA) is a nonsulfated glycosaminoglycan that has been widely used for biomedical applications. Here, we have analyzed the effect of HA on the rescue of primary cells under stress as well as its potential to recover muscle atrophy and validated the developed model in vitro using primary muscle cells derived from rats. The potentials of different HAs were elucidated through comparative analyses using pharmaceutical grade a) high (HHA) and b) low molecular weight (LHA) hyaluronans, c) hybrid cooperative complexes (HCC) of HA in three experimental set-ups. The cells were characterized based on the expression of myogenin, a muscle-specific biomarker, and the proliferation was analyzed using Time-Lapse Video Microscopy (TLVM). Cell viability in response to H2O2 challenge was evaluated by 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, and the expression of the superoxide dismutase enzyme (SOD-2) was assessed by western blotting. Additionally, in order to establish an in vitro model of atrophy, muscle cells were treated with tumor necrosis factor-alpha (TNF-α), along with hyaluronans. The expression of Atrogin, MuRF-1, nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-kB), and Forkhead-box-(Fox)-O-3 (FoxO3a) was evaluated by western blotting to elucidate the molecular mechanism of atrophy. The results showed that HCC and HHA increased cell proliferation by 1.15 and 2.3 folds in comparison to un-treated cells (control), respectively. Moreover, both pre- and post-treatments of HAs restored the cell viability, and the SOD-2 expression was found to be reduced by 1.5 fold in HA-treated cells as compared to the stressed condition. Specifically in atrophic stressed cells, HCC revealed a noteworthy beneficial effect on the myogenic biomarkers indicating that it could be used as a promising platform for tissue regeneration with specific attention to muscle cell protection against stressful agents.

Notoginsenoside R1 protects boar sperm during liquid storage at 17°C.

Reactive oxygen species (ROS) damage mammalian sperm during liquid storage. Notoginsenoside R1 (NR1) is a compound isolated from the roots of Panax notoginseng; it has powerful ROS-scavenging activities. This work hypothesized that the antioxidant capacity of NR1 could improve boar sperm quality and fertility during liquid storage. During liquid storage at 17°C, the supplementation of semen extender with NR1 (50 µM) significantly improved sperm motility, membrane integrity and acrosome integrity after 5 days of preservation. NR1 treatment also reduced ROS and lipid peroxidation (LPO) levels at day 5 (p <0.05). Higher glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) levels and sperm-zona pellucida binding capacity were observed in the 50 µM NR1 group than those in the control group at day 7 (p <0.05). Importantly, statistical analysis of the fertility of 200 sows indicated that addition of NR1 to the extender improved the fertility parameters of boar spermatozoa during liquid storage at 17°C (p <0.05). These results demonstrate the practical feasibility of using 50 µM NR1 as an antioxidant in boar extender during liquid storage at 17°C, which is beneficial to both spermatozoa quality and fertility.

Vitamin C administration attenuated artemether induced hepatic injury in rats / La aAdministración de vitamina C atenúa la lesión hepática inducida por artemeter en ratas

This research was designed to investigate the potential protective effect of vitamin C supplementation against hepatocyte ultrastructural alterations induced by artemether (antimalarial drug) administration. Twenty-four adult male albino rats were used in this study and were divided into four groups (n=6). Group I served as a control and rats in group II administrated artemether (4 mg/kg B.W) orally for three consecutive days. Group III administered artemether plus a low dose of vitamin C (2.86 mg/kg/l water) while group IV received artemether plusa high dose of vitamin C (8.56 mg/kg). At the end of the experimental period (14 days), the harvested liver tissues were examined by transmission electron microscopy (TEM), and blood samples were assayed for biomarkers of liver injury and oxidative stress. Artemether significantly (p<0.05) augmented biomarkers of liver injury such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and oxidative stress such as superoxide dismutase (SOD), Glutathione Peroxidase (GPX), and caused degeneration and damage of the rough endoplasmic reticulum and disrupted mitochondria. The blood sinusoids were also damaged with distortion of their canaliculi. Administration of vitamin C showed improvement of liver biomarkers, and liver parenchyma, especially in a high dose of vitamin C.We concludes that vitamin C is a partial protective agent against artemether-induced liver injury.

Esta investigación fue diseñada para investigar el posible efecto protector de la vitamina C contra las alteraciones ultraestructurales de los hepatocitos, inducidas por la administración de arteméter (medicamento antipalúdico). En el estudio se utilizaron 24 ratas albinas macho adultas y se dividieron en cuatro grupos (n = 6). El grupo I fue designado como control y las ratas en el grupo II se adminstró Arteméter (4 mg / kg de peso corporal) por vía oral durante tres días consecutivos. En el grupo III se administró arteméter, además de una dosis baja de vitamina C (2,86 mg / kg / l de agua) mientras que el grupo IV recibió arteméter más una dosis alta de vitamina C (8,56 mg / kg). Al final del período experimental (14 días), los tejidos hepáticos recolectados se examinaron por microscopía electrónica de transmisión (MET), y las muestras de sangre se analizaron en busca de biomarcadores de daño hepático y estrés oxidativo. El arteméter aumentó significativamente (p <0,05) los biomarcadores de daño hepático como alanina aminotransferasa (ALT), aspartato aminotransferasa (AST) y estrés oxidativo como superóxido dismutasa (SOD), glutatión peroxidasa (GPX) y causó degeneración y daño de la retículo endoplásmico rugoso y mitocondrias alteradas. Los sinusoides sanguíneos también fueron dañados con la distorsión de sus canalículos. La administración de vitamina C mostró una mejoría de los biomarcadores hepáticos y el parénquima hepático, especialmente en una dosis alta de vitamina C. Concluimos que la vitamina C es un agente protector parcial contra la lesión hepática inducida por arteméter.