Evaluation of the antioxidative potential of diisopropyldithiocarbamates sodium salt on diclofenac-induced toxicity in male albino rats.

Diclofenac (DIC) is a non-steroidal anti-inflammatory drug (NSAID) which is known to induce oxidative stress. Dithiocarbamates are compounds with proven antioxidant effect. The aim of the present study was to investigate the antioxidant capacity of diisopropyldithiocarbamates sodium salt (a synthetized compound) (Na(i-Pr2dtc)) against diclofenac-induced toxicity in the testes of male Wistar albino rats. The animals were assigned into six groups of six rats each. Group 1 (control) received corn oil, Groups 2, 3, 4, 5, 6 received DIC (100 mg/kg), DIC and (Na(i-Pr2dtc) (30 mg/kg), DIC and vitamin E (30 mg/kg), (Na(i-Pr2dtc) (30 mg/kg) and vitamin E only respectively. Our findings show that treatment with DIC significantly reduced superoxide dismutase (SOD) activity by 42% compared to normal control (NC) animals. In DIC treated group, Na(i-Pr2dtc) caused a 17% elevation of catalase (CAT) activity compared to DIC only group. Reduced glutathione level was significantly reduced in DIC only treated group when compared with DIC and VIT E treated group. Photomicrographs of testis from Na(i-Pr2dtc) treated rats showed normal seminiferous epithelium with no lesions. In conclusion, Na(i-Pr2dtc) has antioxidant properties.

The levels of oxidative stress in a combination of stress factors.

We studied the effect of the combined action of ionizing radiation and induced immobilization stress on the lipid peroxidation process and antioxidant protection of organs (mesenteric lymph nodes, spleen, adrenal glands, thymus, and liver) and immune cels - the blood lymphocytes. Results were obtained on the role of free-radical oxidation in combination with exposure to ionizing radiation and immobilization stress at an early stage in the experiment. Gamma radiation in the acute period resulted in significant changes in lipoperoxidation and antioxidant systems. The first period of immobilization stress was marked by the imbalance of LPO-AOS systems disturbance with an accumulation of toxic compounds in tissues which had affected their function. The combined sublethal gamma radiation and immobilization stress disturbed the functional activity of adaptive systems of the body in the early stage of adaptation syndrome. Furthermore, the results show the dominant role of ionizing radiation in it.

Origanum majorana essential oil improves the rat's sexual behavior and testicular oxidative damage induced by imidacloprid via modulating the steroidogenesis pathways.

The neonicotinoid insecticide imidacloprid has been linked to significant reproductive damage in mammals. Origanum majorana essential oil (OME) is a natural herbal product used in the management of many diseases due to its strong antioxidant effects. The oil was hydrodistilled from O. Majorana and analyzed using GC/MS then its possible protective mechanisms against IMI-induced reprotoxicity in male rats were investigated. 28-adult male Wistar rats were divided into 4 groups as follows: group (1) control group, group (2) OME, group (3) IMI, and group (4) IMI + OME. The treatments were applied daily via oral gavage for 60 days. Remarkable abnormalities in both territorial aggressive and sexual behaviors were observed in IMI-treated rats with a significant elevation of serum FSH and LH as well as altered testicular redox status. Along with inhibition of the testicular expression of StAR and aromatase genes and serum total testosterone in addition to abnormal sperm count, viability, motility, and morphology. Histopathological examination showed severe degeneration and necrosis in both germ cells and Leydig cells with atrophy in most of the seminiferous tubules. Co-administration of OME with IMI notably improved all the above-mentioned studied parameters, and restored rats' spermatogenesis, sexual behavior, and favorably modulates the levels of both testosterone and gonadotropic hormones via its potent antioxidant effect. These findings support the use of OME as a fertility enhancer and suggest that it could be used to manage pesticide-induced male infertility.

Celastrol induces ferroptosis in activated HSCs to ameliorate hepatic fibrosis via targeting peroxiredoxins and HO-1.

Ferroptosis is a form of regulated cell death, characterized by excessive membrane lipid peroxidation in an iron- and ROS-dependent manner. Celastrol, a natural bioactive triterpenoid extracted from Tripterygium wilfordii, shows effective anti-fibrotic and anti-inflammatory activities in multiple hepatic diseases. However, the exact molecular mechanisms of action and the direct protein targets of celastrol in the treatment of liver fibrosis remain largely elusive. Here, we discover that celastrol exerts anti-fibrotic effects via promoting the production of reactive oxygen species (ROS) and inducing ferroptosis in activated hepatic stellate cells (HSCs). By using activity-based protein profiling (ABPP) in combination with bio-orthogonal click chemistry reaction and cellular thermal shift assay (CETSA), we show that celastrol directly binds to peroxiredoxins (PRDXs), including PRDX1, PRDX2, PRDX4 and PRDX6, through the active cysteine sites, and inhibits their anti-oxidant activities. Celastrol also targets to heme oxygenase 1 (HO-1) and upregulates its expression in activated-HSCs. Knockdown of PRDX1, PRDX2, PRDX4, PRDX6 or HO-1 in HSCs, to varying extent, elevated cellular ROS levels and induced ferroptosis. Taken together, our findings reveal the direct protein targets and molecular mechanisms via which celastrol ameliorates hepatic fibrosis, thus supporting the further development of celastrol as a promising therapeutic agent for liver fibrosis.

Comparative study of the antioxidant activity of the essential oils of five plants against the H2O2 induced stress in Saccharomyces cerevisiae.

The purpose of this work was to investigate the protective effect of five essential oils (EOs); Rosmarinus officinalis, Thymus vulgaris, Origanum compactum Benth., Eucalyptus globulus Labill. and Ocimum basilicum L.; against oxidative stress induced by hydrogen peroxide in Saccharomyces cerevisiae. The chemical composition of the EOs was analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC/MS). The in vitro antioxidant activity was evaluated and the protective effect of EOs was investigated. Yeast cells were pretreated with different concentrations of EOs (6.25-25 µg/ml) for an hour then incubated with H2O2 (2 mM) for an additional hour. Cell viability, antioxidants (Catalase, Superoxide dismutase and Glutathione reductase) and metabolic (Succinate dehydrogenase) enzymes, as well as the level of lipid peroxidation (LPO) and protein carbonyl content (PCO) were evaluated. The chemical composition of EOs has shown the difference qualitatively and quantitatively. Indeed, O. compactum mainly contained Carvacrol, O. basilicum was mainly composed of Linalool, T. vulgaris was rich in thymol, R. officinalis had high α-Pinene amount and for E. globulus, eucalyptol was the major compound. The EOs of basil, oregano and thyme were found to possess the highest amount of total phenolic compounds. Moreover, they have shown the best protective effect on yeast cells against oxidative stress induced by H2O2. In addition, in a dose dependent manner of EOs in yeast medium, treated cells had lower levels of LPO, lower antioxidant and metabolic enzymes activity than cells exposed to H2O2 only. The cell viability was also improved. It seems that the studied EOs are efficient natural antioxidants, which can be exploited to protect against damages and serious diseases related to oxidative stress.

AD-MSCs and BM-MSCs Ameliorating Effects on The Metabolic and Hepato-renal Abnormalities in Type 1 Diabetic Rats.

Diabetes mellitus (DM) is one of the most serious threats in the 21th century throughout the human population that needs to be addressed cautiously. Nowadays, stem cell injection is considered among the most promising protocols for DM therapy; owing to its marked tissues and organs repair capability. Therefore, our 4 weeks study was undertaken to elucidate the probable beneficial effects of two types of adult mesenchymal stem cells (MSCs) on metabolism disturbance and some tissue function defects in diabetic rats. Animals were classified into 4 groups; the control group, the diabetic group, the diabetic group received a single dose of adipose tissue-derived MSCs and the diabetic group received a single dose of bone marrow-derived MSCs. Herein, both MSCs treated groups markedly reduced hyperglycemia resulting from diabetes induction via lowering serum glucose and rising insulin and C-peptide levels, compared to the diabetic group. Moreover, the increased lipid fractions levels were reverted back to near normal values as a consequence to MSCs injection compared to the diabetic untreated rats. Furthermore, both MSCs types were found to have hepato-renal protective effects indicated through the decreased serum levels of both liver and kidney functions markers in the treated diabetic rats. Taken together, our results highlighted the therapeutic benefits of both MSCs types in alleviating metabolic anomalies and hepato-renal diabetic complications.

Artemisia judaica L. diminishes diabetes-induced reproductive dysfunction in male rats via activation of Nrf2/HO-1-mediated antioxidant responses.

Diabetes mellitus is a well-known danger element for the progression of male reproductive dysfunctions. Available evidence supports oxidative stress to be the underlying mechanism for the manifestation of testicular dysfunctions during diabetes, and this relation represents an attractive target to antagonize these complications. Artemisia judaica L. is known to have antidiabetic and antioxidant characteristics. The possible protective effect of Artemisia judaica against diabetes-induced testicular disorders was not explored. In this investigation, we planned to estimate the possible protective effect of Artemisia judaica extract against diabetes-induced testicular disorders in male rats. The blood levels of insulin, glucose, glycosylated hemoglobin, testosterone, luteinizing hormone and follicle stimulating hormone were evaluated in rats after 12 weeks of Artemisia judaica treatment. Further, oxidative stress markers were determined in their testicular tissue. Epididymal fluid and testicular histological changes were also assessed. Expression of proliferating cell nuclear antigen has been evaluated in testis. Testicular mRNA expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 as the significant transcription factors in controlling antioxidant system were evaluated by real-time polymerase chain reaction. Artemisia judaica extracts have the ability to ameliorate the elevation in the serum glucose and blood glycosylated hemoglobin and the reduction in insulin, testosterone, follicle stimulating hormone and luteinizing hormone caused by streptozotocin-induced diabetes. It induced a significant recovery of the testicular oxidative stress markers, sperm characteristics and improved histopathological findings of the testes. Treatment with Artemisia judaica extracts led to an increase in proliferating cell nuclear antigen protein expression. Reduction of testicular oxidative stress potential in streptozotocin-treated groups was confirmed by upregulation of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1.

Recommendations for the use of the acetaminophen hepatotoxicity model for mechanistic studies and how to avoid common pitfalls.

Acetaminophen (APAP) is a widely used analgesic and antipyretic drug, which is safe at therapeutic doses but can cause severe liver injury and even liver failure after overdoses. The mouse model of APAP hepatotoxicity recapitulates closely the human pathophysiology. As a result, this clinically relevant model is frequently used to study mechanisms of drug-induced liver injury and even more so to test potential therapeutic interventions. However, the complexity of the model requires a thorough understanding of the pathophysiology to obtain valid results and mechanistic information that is translatable to the clinic. However, many studies using this model are flawed, which jeopardizes the scientific and clinical relevance. The purpose of this review is to provide a framework of the model where mechanistically sound and clinically relevant data can be obtained. The discussion provides insight into the injury mechanisms and how to study it including the critical roles of drug metabolism, mitochondrial dysfunction, necrotic cell death, autophagy and the sterile inflammatory response. In addition, the most frequently made mistakes when using this model are discussed. Thus, considering these recommendations when studying APAP hepatotoxicity will facilitate the discovery of more clinically relevant interventions.

Insights into the ameliorative effect of oleic acid in rejuvenating phenylhydrazine induced oxidative stress mediated morpho-functionally dismantled erythrocytes.

Phenylhydrazine (PHZ), an intermediate in the synthesis of fine chemicals is toxic for human health and environment. Despite of having severe detrimental effects on different physiological systems, exposure of erythrocytes to PHZ cause destruction of haemoglobin and membrane proteins leading to iron release and complete haemolysis of red blood cells (RBC). Involvement of oxidative stress behind such action triggers the urge for searching a potent antioxidant. The benefits of consuming olive oil is attributed to its 75% oleic acid (OA) content in average. Olive oil is the basic component of Mediterranean diet. Hence, OA has been chosen in our present in vitro study to explore its efficacy against PHZ (1 mM) induced alterations in erythrocytes. Four different concentrations of OA (0.01 nM, 0.02 nM, 0.04 nM and 0.06 nM) were primarily experimented with, among which 0.06 nM OA has shown to give maximal protection. This study demonstrates the capability of OA in preserving the morphology, intracellular antioxidant status and the activities of metabolic enzymes of RBCs that have been diminished by PHZ, through its antioxidant mechanisms. The results of the present study firmly establish OA as a promising antioxidant for conserving the health of erythrocyte from PHZ toxicity which indicate toward future possible use of OA either singly or in combination with other dietary components for protection of erythrocytes against PHZ induced toxic cellular changes.

Cinnamon oil against acetaminophen-induced acute liver toxicity by attenuating inflammation, oxidative stress and apoptosis.

Acetaminophen (APAP) is used as a primary drug due to its antipyretic and analgesic activity. The mechanism of action of APAP toxicity in the liver is due to the depletion of glutathione which elicited free radicals generation. Therefore, the objective of our work is to investigate the APAP induced liver damage and its repair by free radical scavenging activity of cinnamon oil (CO) in male Wistar rats. To investigate the effects of CO at different doses (50, 100 and 200 mg/kg b.w.), animals were given a single oral dose of CO per day for 14 days between 12:00-1:00 PM. The biochemical changes, imbalance in oxidative markers, interleukins, caspases and histopathological studies were determined for quantifying the hepatoprotective effect of CO. One dose of APAP (2 g/kg b.w.) results in significant hepatotoxicity and marked increase the serum markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin, albumin, total protein, content of lipid peroxidation (LPO), interleukins (IL-1ß, IL-6), caspase-3, -9 expression, DNA fragmentation and histopathological changes were observed. Significant decrease in the levels of LPO, interleukins IL-1ß, IL-6, caspase-3, -9 expressions, qualitative as well as quantitative determination of DNA fragments and histopathological changes were reversed by the administration of CO dose dependently. Furthermore, it also restores the depleted activity of antioxidative enzymes. Our study shows that an imbalance in the oxidative parameter in the liver by APAP is restored by treating the animals with CO.

Gastroprotective and anti-inflammatory effects of Prunus cerasus phytochemicals and their possible mechanisms of action.

Prunus cerasus (P. cerasus) is an alternative-medicine used traditionally for amelioration of chronic-ailments marked by elevation in oxidative-stress like neuropathy. The oxidative-stress control was reported to ameliorate the inflammatory-process. This study aimed to phytochemically-investigate P. cerasus most-active phytochemicals utilizing in-vivo biological models to explore their gastroprotective, anti-inflammatory, and antinociceptive potentials and their possible mechanisms of action. Sonication with EtAc was used to extract P. cerasus fruit (Scf), and seed (Scs). The phytochemical-investigation of Scf was performed by RP-HPLC, while that of Scs was explored utilizing GC-FID. A bio-guided-fraction and isolation method was done utilizing column-chromatography, and have shown that cyanidin-3-glucoside (Cy3G) was the most-active constituent in Scf, while linoleic-acid (LA) was the most-active constituent in Scs. Scf, Scs, Cy3G, and LA significantly (p ˂ 0.05) protected the gastric-mucosa against HCl/EtOH-induced gastric-lesions. Scs (200 mg/kg) has shown the most gastroprotective-potentials, and had comparable-results to ranitidine (50 mg/kg). Scf, Scs, Cy3G, and LA have shown significant anti-inflammatory and antinociceptive potentials against carrageenan induced-edema and nociceptive-pain, respectively, where Scs (200 mg/kg) has shown the most anti-inflammatory and antinociceptive potentials, and had comparable results to ibuprofen (100 mg/kg). Scf, Scs, Cy3G, and LA have counter-acted carrageenan-induced oxidative-stress markers, with increased serum-catalase and reduced-glutathione levels, and decreased lipid-peroxidation. Histopathological-studies demonstrated gastroprotective potentials, regeneration and improvement of the spleen-structural architecture when treated with highest doses of Scs and Scf. The reduction of the pro-inflammatory TNF-alpha and IL-6, and elevation the anti-inflammatory factor IL-10 levels, spleen regenerative-capacity and oxidative-stress amelioration might be the main-mechanism responsible for P. cerasus anti-inflammatory potentials. P. cerasus appears to aid in ameliorating the inflammatory process, and reducing pain-thresholds while preserving the stomach.

Protective effect of a polyherbal bioactive fraction in propylthiouracil-induced thyroid toxicity in ratsby modulation of the hypothalamic-pituitary-thyroid and hypothalamic-pituitary-adrenal axes.

Hypothyroidism is the most frequent consequence of the interaction of a large variety of drugs, environmental pollutants and industrial chemicals with the thyroid gland. It is associated with diminished endocrine function which may lead to hyperlipidemia, diabetes, Alzheimer's disease, weight gain, and other metabolic disorders. The present study evaluates the pro-thyroid activity of a bioactive fraction from a polyherbal teabag in rats with hypothyroidism induced by propylthiouracil. The teabag was formulated to stimulate synthesis and/or release of T4 and affectthe conversion of T4 to T3. Phytoconstituents of the polyherbal teabag are potent antioxidants that may be responsible for the pro-thyroid activity. The tea-extract (1000 mg) was found to contain 1076 µg of gallic acid and 1131 µg of rutin from HPTLC analysis. Rats received propylthiouracil (8 mg/kg) for the first 15days followed by the polyherbal tea-extract (500, 1000 and 1500 mg/kg), the standard drug levothyroxine (0.1 mg/kg), aerobic exercise, and a combination of tea-extract (1000 mg/kg) and aerobic exercise daily along with propylthiouracil for the next 30 days. Finally, rats received their respective treatments alone without propylthiouracil for 15 more days. Lipid profile and levels of glucose, insulin, T3, T4, TSH, cortisol, homocysteine, creatinine, uric acid, malondialdehyde, glucose-6 phosphatase, and endogenous antioxidants were determined. All treatments attenuated significantly the propylthiouracil-elevated TSH, homocysteine, creatinine, uric acid, glucose-6-phosphatase, insulin, and malondialdehyde levels, and restored favorably the propylthiouracil-altered lipid profile, T3, T4, and endogenous antioxidant levels. The polyherbal tea-extract (1000 and 1500 mg/kg) treatment and thecombination treatment of tea-extract (1000 mg/kg) with aerobic exercise displayed significant restoration of the suboptimalthyroid function. This may be due to a favorablemodulation ofthe hypothalamic-pituitary-thyroid and the hypothalamic-pituitary-adrenal axes.

Toxicity profile of honey and ghee, when taken together in equal ratio.

Honey and ghee are an essential component of our diet. They play an important role like anti-inflammatory, antioxidative, antimicrobial, etc. It is written in Charak Samhita that an equal mixture of honey and ghee turn into a harmful component for health. This study was designed to explore the mechanism of toxicity through the biochemical and histological parameters in Charles foster rats (24 rats were used). We have divided these rats into four groups (n = 6) - normal, honey (0.7 ml/100 g bw), ghee (0.7 ml/100 g bw), and honey + ghee (1:1) (1.5 ml/100 g bw). Treatment was given orally for 60 days. All rats were sacrificed on 61 days. Biochemical parameters like liver function test, kidney function test, Oxidative stress, Glycemic, and some protein modification parameters were done in blood plasma. We found weight loss, hair loss, red patches on ear, and increased liver function test, oxidative stress, Amadori product formation, advanced glycation end-product formation, dipeptidyl protease (DPP-4) and decreased incretins (glucagon-like peptide-1(GLP-1) and gastric inhibitory polypeptide (GIP)) in honey + ghee group. H&E and immunohistochemistry results showed mild inflammation in liver tissue but no changes in the kidney, intestine and, pancreas. Thus it concluded that the increased formation of Amadori product, DPP-4 activity and low incretins (GLP-1, GIP) activity resulting high postprandial hyperglycemic response could be collectively responsible for oxidative stress-mediated toxicity of honey and ghee in the equal mixture.

Vanadium: Risks and possible benefits in the light of a comprehensive overview of its pharmacotoxicological mechanisms and multi-applications with a summary of further research trends.

BACKGROUND: Vanadium (V) is an element with a wide range of effects on the mammalian organism. The ability of this metal to form organometallic compounds has contributed to the increase in the number of studies on the multidirectional biological activity of its various organic complexes in view of their application in medicine. OBJECTIVE: This review aims at summarizing the current state of knowledge of the pharmacological potential of V and the mechanisms underlying its anti-viral, anti-bacterial, anti-parasitic, anti-fungal, anti-cancer, anti-diabetic, anti-hypercholesterolemic, cardioprotective, and neuroprotective activity as well as the mechanisms of appetite regulation related to the possibility of using this element in the treatment of obesity. The toxicological potential of V and the mechanisms of its toxic action, which have not been sufficiently recognized yet, as well as key information about the essentiality of this metal, its physiological role, and metabolism with certain aspects on the timeline is collected as well. The report also aims to review the use of V in the implantology and industrial sectors emphasizing the human health hazard as well as collect data on the directions of further research on V and its interactions with Mg along with their character. RESULTS AND CONCLUSIONS: Multidirectional studies on V have shown that further analyses are still required for this element to be used as a metallodrug in the fight against certain life-threatening diseases. Studies on interactions of V with Mg, which showed that both elements are able to modulate the response in an interactive manner are needed as well, as the results of such investigations may help not only in recognizing new markers of V toxicity and clarify the underlying interactive mechanism between them, thus improving the medical application of the metals against modern-age diseases, but also they may help in development of principles of effective protection of humans against environmental/occupational V exposure.

Comparative effect of indomethacin (IndoM) on the enzymes of carbohydrate metabolism, brush border membrane and oxidative stress in the kidney, small intestine and liver of rats.

Indomethacin (IndoM) has prominent anti-inflammatory and analgesic-antipyretic properties. However, high incidence and severity of side-effects on the structure and functions of the kidney, liver and intestine limits its clinical use. The present study tested the hypothesis that IndoM causes multi-organ toxicity by inducing oxidative stress that alters the structure of various cellular membranes, metabolism and hence functions. The effect of IndoM was determined on the enzymes of carbohydrate metabolism, brush border membrane (BBM) and oxidative stress in the rat kideny, liver and intestine to understand the mechanism of IndoM induced toxicity. Adult male Wister rats were given IndoM (20 mg/kg) intra-peritoneally in sodium bicarbonate twice a day for 3 d. The body weights of the rats were recorded before and after experimental procedure. IndoM administration significantly increased blood urea nitrogen, serum creatinine, cholesterol and alkaline phosphatase but inorganic phosphate indicating IndoM induced renal, hepatic and intestinal toxicity. Activity of lactate dehydrogenase along with glucose-6- and fructose-1, 6-bis phosphatase, glucose-6-phosphate dehydrogenase and NADP-malic enzyme increased but malate dehydrogenase decreased in all tissues. Lipid peroxidation (LPO) significantly increased whereas the antioxidant enzymes decreased in all rat tissues studied. The results indicate that IndoM administration caused severe damage to kidney, liver and intestine by icreasing LPO, suppressing antioxidant enzymes and inhibiting oxidative metablolism. The energy dependence was shifted to anaerobic glycolysis due to mitochondrial damage supported by increased gluconeogenesis to provide more glucose to meet energy requirements.

Computational Modeling of Oxidative Stress in Fatty Livers Elucidates the Underlying Mechanism of the Increased Susceptibility to Ischemia/Reperfusion Injury.

QUESTION: Donor liver organs with moderate to high fat content (i.e. steatosis) suffer from an enhanced susceptibility to ischemia/reperfusion injury (IRI) during liver transplantation. Responsible for the cellular injury is an increased level of oxidative stress, however the underlying mechanistic network is still not fully understood. METHOD: We developed a phenomenological mathematical model of key processes of hepatic lipid metabolism linked to pathways of oxidative stress. The model allows the simulation of hypoxia (i.e. ischemia-like conditions) and reoxygenation (i.e. reperfusion-like conditions) for various degrees of steatosis and predicts the level of hepatic lipid peroxidation (LPO) as a marker of cell damage caused by oxidative stress. RESULTS & CONCLUSIONS: Our modeling results show that the underlying feedback loop between the formation of reactive oxygen species (ROS) and LPO leads to bistable systems behavior. Here, the first stable state corresponds to a low basal level of ROS production. The system is directed to this state for healthy, non-steatotic livers. The second stable state corresponds to a high level of oxidative stress with an enhanced formation of ROS and LPO. This state is reached, if steatotic livers with a high fat content undergo a hypoxic phase. Theoretically, our proposed mechanistic network would support the prediction of the maximal tolerable ischemia time for steatotic livers: Exceeding this limit during the transplantation process would lead to severe IRI and a considerable increased risk for liver failure.

The effect of short-term coenzyme Q10 supplementation and pre-cooling strategy on cardiac damage markers in elite swimmers.

Strenuous physical exercise and hyperthermia may paradoxically induce oxidative stress and adverse effects on myocardial function. The purpose of this study was to investigate the effect of 14-d coenzyme Q10 (CoQ10) supplementation and pre-cooling on serum creatine kinase-MB (CK-MB), cardiac Troponin I (cTnI), myoglobin (Mb), lactate dehydrogenase (LD), total antioxidant capacity (TAC), lipid peroxidation (LPO) and CoQ10 concentration in elite swimmers. In total, thirty-six healthy males (mean age 17 (sd 1) years) were randomly selected and divided into four groups of supplementation, supplementation with pre-cooling, pre-cooling and control. During an eighteen-session protocol in the morning and evening, subjects attended speed and endurance swimming training sessions for 5 km in each session. Blood sampling was done before (two stages) and after (two stages) administration of CoQ10 and pre-cooling. ANCOVA and repeated measurement tests with Bonferroni post hoc test were used for the statistical analysis of the data. There was no significant statistical difference among groups for the levels of CK-MB, cTnI, Mb, LD, TAC, LPO and CoQ10 at the presampling (stages 1 and 2) (P>0·05). However, pre-cooling and control groups show a significant increase in the levels of CK-MB, cTnI, Mb, LD and LPO compared with the supplementation and supplementation with pre-cooling groups in the post-sampling (stages 1 and 2) (P<0·05), except for the TAC and CoQ10. Consequently, CoQ10 supplementation prevents adverse changes of myocardial damage and oxidative stress during swimming competition phase. Meanwhile, the pre-cooling strategy individually has no desired effect on the levels of CK-MB, cTnI, Mb, LD, LPO, TAC and CoQ10.

Nephrotoxicity and highly active antiretroviral therapy: Mitigating action of Momordica charantia.

Momordica charantia (M. charantia) is known for its antioxidant and antidiabetic properties. The aim of this study is to investigate the renoprotective effects of M. charantia in rats following treatment with highly active antiretroviral therapy (HAART) regimen triplavar. Adult male Sprague-Dawley rats weighing 178.1-220.5 g (n = 36) were divided into six groups (A-F) with each group comprising of six (n = 6) rats. The drugs and extract were administered via oral gavage. The therapeutic dose of triplavar was adjusted using the human therapeutic dose equivalent for the rat model. Animals were euthanized on the tenth week with kidneys removed for examination and blood obtained via cardiac puncture. Levels of oxidative stress enzymes (superoxide dismutase-SOD, catalase-CAT, and reduced glutathione-GSH) were significantly lowered in all groups not receiving M. charantia. The levels of thiobarbituric acid reactive substances (TBARS) were increased resulting in free radical formation via auto-oxidation. Renal parameters showed no albuminuria, normal blood urea nitrogen (BUN), serum creatinine (SCr) and electrolytes in groups treated with M. charantia. HAART treated (Group B) showed severe albuminuria, a significantly (p < 0.05) raised BUN and SCr and gross electrolyte disturbances. Blood glucose levels were significantly raised in groups not receiving the adjuvant M. charantia (p < 0.05). Histopathology in HAART treated animals showed glomerular capillary abnormalities and cellular infiltrations while M. charantia treated animals showed an essentially normal glomerular appearance with capillary loops and normal cytoarchitecture. In conclusion M. charantia extract administration improved blood glucose levels, restored renal histology, reinstate renal function, reduce body weight loss and restores hyperglycemia.

The para isomer of dinitrobenzene disrupts redox homeostasis in liver and kidney of male wistar rats.

BACKGROUND: Para-Dinitrobenzene (p-DNB) is one of the isomers of dinitrobenzene which have been detected as environmental toxicants. Skin irritation and organ toxicities are likely for industrial workers exposed to p-DNB. This study evaluated the effect of sub-chronic exposure of rats to p-DNB on cellular redox balance, hepatic and renal integrity. METHODS: Forty eight male Wistar rats weighing 160-180 g were administered 50, 75, 1000 and 2000 mg/kg b.wt (body weight) of p-DNB or an equivalent volume of vehicle (control) orally and topically for 14 days. After the period of treatment, the activities of kidney and liver catalase (CAT), alkaline phosphatase (ALP) and superoxide dismutase (SOD) as well as extent of renal and hepatic lipid peroxidation (LPO) were determined. Serum ALP activity and plasma urea concentration were also evaluated. RESULTS: Compared with control animals, p-DNB -administered rats showed decrease in the body and relative kidney and liver weights as well as increased renal and hepatic hydrogen peroxide and lipid peroxidation levels accompanied by decreased superoxide dismutase and catalase activities. However, p-DNB caused a significant increase in plasma urea concentration and serum, liver and kidney ALP activities relative to control. In addition, p-DNB caused periportal infiltration, severe macro vesicular steatosis and hepatic necrosis in the liver. CONCLUSIONS: Our findings show that sub-chronic oral and sub-dermal administration of p-DNB may produce hepato-nephrotoxicity through oxidative stress.

Blood brain barrier permeability of (-)-epigallocatechin gallate, its proliferation-enhancing activity of human neuroblastoma SH-SY5Y cells, and its preventive effect on age-related cognitive dysfunction in mice.

BACKGROUND: The consumption of green tea catechins (GTCs) suppresses age-related cognitive dysfunction in mice. GTCs are composed of several catechins, of which epigallocatechin gallate (EGCG) is the most abundant, followed by epigallocatechin (EGC). Orally ingested EGCG is hydrolyzed by intestinal biota to EGC and gallic acid (GA). To understand the mechanism of action of GTCs on the brain, their permeability of the blood brain barrier (BBB) as well as their effects on cognitive function in mice and on nerve cell proliferation in vitro were examined. METHODS: The BBB permeability of EGCG, EGC and GA was examined using a BBB model kit. SAMP10, a mouse model of brain senescence, was used to test cognitive function in vivo. Human neuroblastoma SH-SY5Y cells were used to test nerve cell proliferation and differentiation. RESULTS: The in vitro BBB permeability (%, in 30 min) of EGCG, EGC and GA was 2.8±0.1, 3.4±0.3 and 6.5±0.6, respectively. The permeability of EGCG into the BBB indicates that EGCG reached the brain parenchyma even at a very low concentration. The learning ability of SAMP10 mice that ingested EGCG (20 mg/kg) was significantly higher than of mice that ingested EGC or GA. However, combined ingestion of EGC and GA showed a significant improvement comparable to EGCG. SH-SY5Y cell growth was significantly enhanced by 0.05 µM EGCG, but this effect was reduced at higher concentrations. The effect of EGC and GA was lower than that of EGCG at 0.05 µM. Co-administration of EGC and GA increased neurite length more than EGC or GA alone. CONCLUSION: Cognitive dysfunction in mice is suppressed after ingesting GTCs when a low concentration of EGCG is incorporated into the brain parenchyma via the BBB. Nerve cell proliferation/differentiation was enhanced by a low concentration of EGCG. Furthermore, the additive effect of EGC and GA suggests that EGCG sustains a preventive effect after the hydrolysis to EGC and GA.