Protective effect of coenzyme Q10 in cyclophosphamide-induced kidney damage in rats.

OBJECTIVE: We aimed to investigate the effect of coenzyme q10 on cyclophosphamide-induced kidney damage in rats. METHODS: A total of 30 female Wistar-Albino rats were utilized to form three groups. In group 1 (control group) (n=10), no drugs were given. In group 2 (cyclophosphamide group) (n=10), 30 mg/kg intraperitoneal cyclophosphamide was administered for 7 days. In group 3 (cyclophosphamide+coenzyme q10 group) (n=10), 30 mg/kg cyclophosphamide and 10 mg/kg coenzyme q10 were given for 7 days via intraperitoneal route. Right kidneys were removed in all groups. Blood malondialdehyde levels and activities of catalase and superoxide dismutase were measured. Histopathological damage was evaluated by examining the slides prepared from kidney tissue using a light microscope. RESULTS: Tissue damage was significantly higher in the cyclophosphamide group than in the cyclophosphamide+coenzyme q10 group (p<0.05). The malondialdehyde levels were significantly higher and the activities of superoxide dismutase and catalase were lower in the cyclophosphamide group than in the cyclophosphamide+coenzyme q10 group (p<0.05). CONCLUSION: Coenzyme q10 may be a good option to prevent cyclophosphamide-induced kidney damage.

[Honokiol reduces oxidative stress by activating the SIRT3-MnSOD2 pathway to alleviate hypertriglyceridemia-induced acute pancreatitis in rats].

OBJECTIVE: To determine how honokiol affects the sirtuin-3 (SIRT3)-MnSOD2 pathway and oxidative stress in rats with hypertriglyceridemia-induced acute pancreatitis (HTGP). METHODS: Thirty 4-week-old male SD rats were randomly divided into two groups for normal feeding and high-fat feeding for 4 weeks, after which the rats with normal feeding were randomized into control group and acute pancreatitis (AP) group (n=6), and those with high-fat feeding were divided into hypertriglyceridemia group, HTGP group, and honokiol treatment group (n=6). In AP, HTGP, and honokiol groups, AP models were established by intraperitoneal injection of cerulean; in honokiol group, the rats received an intraperitoneal injection of 5 mg/kg honokiol 15 min after cerulean injection. Serum TG, IL-6, and TNF-α levels were measured 24 h after the treatments, and pathological changes in the pancreas were observed with HE staining; The levels of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione peroxidase (GSH) were measured, and SIRT3 and manganese superoxide dismutase (MnSOD2) expressions were detected using Western blotting and immunohistochemistry. Transmission electron microscopy was used to examine the ultrastructure of pancreatic acinar cells and mitochondria. RESULTS: Compared with the those with normal feeding, the rats with high-fat feeding had significantly elevated serum TG level (P < 0.05). The rat models of AP showed significantly increased serum levels of IL-6, TNF-α, and MDA and decreased GSH level and expressions of SIRT3 and MnSOD2, with obvious edema and inflammatory cell infiltration and enhanced ROS fluorescence intensity in the pancreas and ultrastructural damages of the acinar cells and mitochondria. In rats with HTGP, honokiol treatment significantly decreased serum levels of IL-6, TNF-α, and MDA, increased GSH level and SIRT3 and MnSOD2 expressions, reduced ROS production, and alleviated ultrastructural damage of the acinar cells and mitochondria in the pancreas. CONCLUSION: Honokiol reduce oxidative stress and alleviates pancreatic injuries in HTGP rats possibly by activating the SIRT3-MnSOD2 pathway.

Trilobatin rescues cognitive impairment of Alzheimer's disease by targeting HMGB1 through mediating SIRT3/SOD2 signaling pathway.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with cognitive impairment that currently is uncurable. Previous study shows that trilobatin (TLB), a naturally occurring food additive, exerts neuroprotective effect in experimental models of AD. In the present study we investigated the molecular mechanisms underlying the beneficial effect of TLB on experimental models of AD in vivo and in vitro. APP/PS1 transgenic mice were administered TLB (4, 8 mg· kg-1 ·d-1, i.g.) for 3 months; rats were subjected to ICV injection of Aß25-35, followed by administration of TLB (2.5, 5, 10 mg· kg-1 ·d-1, i.g.) for 14 days. We showed that TLB administration significantly and dose-dependently ameliorated the cognitive deficits in the two AD animal models, assessed in open field test, novel object recognition test, Y-maze test and Morris water maze test. Furthermore, TLB administration dose-dependently inhibited microglia and astrocyte activation in the hippocampus of APP/PS1 transgenic mice accompanied by decreased expression of high-mobility group box 1 (HMGB1), TLR4 and NF-κB. In Aß25-25-treated BV2 cells, TLB (12.5-50 µM) concentration-dependently increased the cell viability through inhibiting HMGB1/TLR4/NF-κB signaling pathway. HMGB1 overexpression abrogated the beneficial effects of TLB on BV2 cells after Aß25-35 insults. Molecular docking and surface plasmon resonance assay revealed that TLB directly bound to HMGB1 with a KD value of 8.541×10-4 M. Furthermore, we demonstrated that TLB inhibited Aß25-35-induced acetylation of HMGB1 through activating SIRT3/SOD2 signaling pathway, thereby restoring redox homeostasis and suppressing neuroinflammation. These results, for the first time, unravel a new property of TLB: rescuing cognitive impairment of AD via targeting HMGB1 and activating SIRT3/SOD2 signaling pathway.

Attenuation of isoprenaline-induced myocardial infarction by Rheum turkestanicum.

BACKGROUND: Oxidative stress plays a major role in the pathogenesis of myocardial infarction. This study evaluated the cardioprotective effects of the hydroalcoholic extract of Rheum turkestanicum on isoprenaline-induced myocardial infarction (MI) in Wistar rats. METHODS: In this study, we used liquid chromatography-mass spectrometry to determine the active compounds present in the extract. Thirty rats were divided to 5 groups (6 rats in each group). The extract was administered orally at the doses of 100 and 300 mg/kg body weight and then a subcutaneous injection of isoprenaline (85 mg/kg) was administered on the 8th and 9th days. Serum levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and creatinine kinase (CPK) were measured using standard commercial kits. Serum activities of superoxide dismutase, catalase, and cardiac levels of thiol and lipid peroxidation were also determined. Hematoxylin and eosin were used for histopathological staining. RESULTS: Phytochemical analysis revealed the presence of 24 compounds in the hydro-ethanolic extract of R. turkestanicum. Isoprenaline increased malondialdehyde (4.002 ± 0178, P < 0.001) while decreased thiol content (101.7 ± 6.186, P < 0.001). Moreover, reduced activities of superoxide dismutase (139 ± 10.88, P < 0.001) and catalase (2.812 ± 0.215, P < 0.001), and elevated levels of LDH (1245 ± 62.28, P < 0.001), CPK (898 ± 23.06, P < 0.001) and CK-MB (697 ± 50.22, P < 0.001) were observed. Pretreatment with the R. turkestanicum extract significantly reduced cardiac markers and increased thiol content as well as the activity of antioxidant enzymes. The extract attenuated the histopathological changes induced by isoprenaline. CONCLUSION: According to the obtained results, R. turkestanicum may be an appropriate candidate to reduce isoprenaline-induced MI through modulation of oxidative stress. Administration of the extract attenuated cardiac enzymes following isoprenaline administration. The cardioprotective action of the extract can be attributed to the bioactive antioxidant ingredients of R. turkestanicum. To identify the precise mechanisms, further investigations are required.

Anti-inflammatory effect of flavonoids from chestnut flowers in lipopolysaccharide-stimulated RAW 264.7 macrophages and acute lung injury in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Chestnut flowers were one of the by-products during chestnut industrial processing. Chestnut (Castanea mollissima Blume) flower is rich in flavonoids and has been used as a traditional medicine to treat a variety of diseases including respiratory disorders for a long history. AIM OF THE STUDY: The present study aims to investigate the potential anti-inflammatory effect of flavonoids from chestnut flower (FCF) in lipopolysaccharide (LPS)-treated RAW 264.7 cells and stimulated acute lung injury (ALI) in mice. MATERIALS AND METHODS: HPLC-ESI-MS/MS was applied to identify flavonoids from Chestnut flower. The ROS content in cells and lung tissue was measured by flow cytometry. The malondialdehyde (MDA) content, superoxide dismutase (SOD) activity and glutathione (GSH) content in cells and bronchoalveolar lavage fluid (BALF) was analyzed by photometry. Furthermore, the level of pro-inflammatory factors was analyzed by ELISA, and the expression of inflammatory gene mRNA by fluorescence quantitative PCR. H&E staining was used to evaluate the degree of lung tissue injury in mice. MPO activity was used to measure the degree of neutrophil infiltration. Total protein content was detected by BCA method. RESULTS: A total of forty-nine flavonoids compounds were tentatively identified in FCF by mass spectrometry analysis. The results of cell experiment suggested that FCF could alleviate oxidative injury via increasing SOD activity and GSH content, as well as inhibiting the production of intracellular ROS and MDA. FCF exerted its protective effect by suppressing the expression of both inducible nitric oxide synthase (iNOS) and cycooxygenase 2 (COX-2) to inhibit the synthesis of pro-inflammatory factors and cytokines, including NO, PGE2, TNF-α, IL-6 and IL-1ß. Besides, FCF treatment could alleviate the thickening of alveolar wall and pulmonary congestion in LPS-treated ALI mice, and significantly inhibit the activity of myeloperoxidas (MPO) and the expression of cytokines in BALF. CONCLUSIONS: FCF could ameliorate inflammation and oxidative stress in LPS-treated inflammation, resulting in an overall improvement in both macroscopic and histological parameters.

Protective effect of Amomum Roxb. essential oils in lipopolysaccharide-induced acute lung injury mice and its metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Several Amomum species are commonly used in food as flavoring agents and traditional Chinese medicine to treat inflammation-related diseases. AIM OF THE STUDY: This study aims to investigate the protective effects of Chinese herbal medicines, including six Amomum Roxb. essential oils (AEOs), against acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice. MATERIALS AND METHODS: The compositions of AEOs were analyzed using gas chromatography - mass spectrometry. RAW264.7 cells were treated with AEOS (0-100 µg/mL) and stimulated with LPS. C57 mice received AEOs (100 mg/kg) via atomization system for seven consecutive days, and then, intratracheal instillation of LPS was applied to establish an in vivo model of acute lung injury. RESULTS: We identified three AEOs demonstrating anti-inflammatory effects and amelioration of LPS-induced lung tissue pathological damage. Furthermore, we found that these AEOs reduced lung wet/dry weight ratios and protein concentrations in the bronchoalveolar lavage fluid of mice with LPS-induced ALI. Additionally, AEOs reduced the levels of malondialdehyde, TNF-α, IL-6, and IL-1ß but increased the levels of superoxide dismutase and catalase in lung tissue, alveolar lavage fluid, and serum samples. We also found that these three AEOs affected proteins related to the TLR4/Myd88/NF-κB pathway. CONCLUSIONS: In summary, our findings revealed that AEOs ameliorate inflammatory and oxidative stress in mice with ALI through the TLR4/Myd88/NF-κB pathway.

Daidzin targets epithelial-to-mesenchymal transition process by attenuating manganese superoxide dismutase expression and PI3K/Akt/mTOR activation in tumor cells.

AIMS: Epithelial-mesenchymal transition (EMT) is a process during which epithelial cells lose their polarity and gain invasive properties to transform into mesenchymal cells. A few recent studies have reported that manganese superoxide dismutase (MnSOD) can effectively modulate EMT phenotype by influencing cellular redox environment via altering the intracellular ratio between O2- and H2O2. Daidzin (DDZ), a naturally occurring isoflavone isolated from Pueraria lobate (Fabaceae), has numerous pharmacologic effects including anti-cholesterol, anti-angiocardiopathy, anti-cancer. However, the potential inhibitory impact of DDZ on cancer metastasis and specifically on the EMT process has not been evaluated. We aimed to evaluate the possible relationship between MnSOD and EMT as well as influence of DDZ on these two processes in colon and prostate carcinoma cells. MAIN METHODS: Cell viability was measured by MTT and real time cell analysis (RTCA) assay. Protein expression level of EMT markers and Akt/mTOR/PI3K signaling pathway were evaluated by Western blot analysis. Expression of EMT markers in cells was observed by immunocytochemistry. Cell invasion and migrations were evaluated by wound healing assay and Boyden chamber assay. KEY FINDINGS: DDZ can block EMT accompanied with down-regulation of MnSOD, fibronectin, vimentin, MMP-9, MMP-2, N-cadherin, twist, and Snail, and up-regulation of occludin and E-cadherin in both unstimulated and TGFß-induced cells. In addition, DDZ exposure also attenuated cell proliferation, invasion, and metastasis by reversing the EMT process in SNU-C2A, DU145, and PC-3 cells. DDZ treatment also modulated activation of PI3K/Akt/mTOR signaling cascades in DU145 cells. Moreover, an overexpression of MnSOD or silencing of MnSOD expression modulated EMT-related proteins, PI3K/Akt/mTOR activation and invasive activity. SIGNIFICANCE: This is first finding on the DDZ in regulating MnSOD and EMT process by targeting PI3K/Akt/mTOR pathway in both colorectal and prostate cancer cell lines. Our data indicated that DDZ might act as a potent suppressor of EMT by affecting MnSOD expression in tumor cells.

In vitro antiaging activity of polyphenol rich Polyalthia longifolia (Annonaceae) leaf extract in Saccharomyces cerevisiae BY611 yeast cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Polyalthia longifolia var. angustifolia Thw. (Annonaceae) is commonly used in traditional medicine as a tonic for rejuvenation and exhibiting good antioxidant activities. AIM OF THE STUDY: To evaluate P. longifolia methanolic leaf extract (PLME) antiaging activity at 1 mg/mL in Saccharomyces cerevisiae BY611 yeast. MATERIALS AND METHODS: The antiaging effect of PLME was studied via replicative lifespan assay, antioxidative stress assays, reactive oxygen species (ROS) determination, reduced glutathione (GSH) determination, superoxide dismutase (SOD) and Sirtuin 1 (SIRT1) genes regulation studies and SOD and SIRT1 proteins activities. RESULTS: The PLME treatment increased the growth and prolonged the lifespan of the yeast significantly (p < 0.05) compared to the untreated yeast group. Besides, the PLME also protected the yeast from oxidative stress induced by 4-mM-H2O2 via decreasing (p < 0.05) the ROS from 143.207 to 127.223. The antioxidative action of PLME was proved by spot assay. Phloxine B staining was further confirmed the PLME antioxidative action of PLME, where more whitish-pink live yeast cells were observed. In addition, the PLME also enhanced GSH content significantly (p < 0.05) in yeast treated with PLME from 16.81 to 25.31 µmol. Furthermore, PLME increased the SOD and SIRT1 genes expression significantly (p < 0.05) with ΔCt values of 1.11 and 1.15, respectively. The significantly (p < 0.05) elevated SOD and SIRT1 protein activities were recorded as 51.54 U/mg Prot and 1716 ng/mL, respectively. CONCLUSIONS: PLME exhibited good antiaging activities in S. cerevisiae, by modulating oxidative stress, enhancing GSH content, and increasing SOD and SIRT1 genes expression.

Anti-diabetic potential of ß-boswellic acid and 11-keto-ß-boswellic acid: Mechanistic insights from computational and biochemical approaches.

ß-Boswellic acid (ß-BA) and 11-keto-ß-boswellic acid (ß-KBA) are crucial bioactive compounds, mostly isolated from frankincense. These compounds are known for their potent anticancer and anti-inflammatory activities. Herein, we have explored the complete anti-diabetic potential of ß-BA and ß-KBA with detailed parameters. This research revealed that treatment with ß-BA and ß-KBA at a dose of 1, 2, and 10 mg/kg body weight for 21 days significantly improved body weight loss, water consumption, and specifically the concentration of blood glucose level (BGL) in diabetic animals, which indicated that the ß-BA and ß-KBA possess strong anti-diabetic activities. Serum total superoxide dismutase (SOD) and malondialdehyde (MDA) assays were also performed to evaluate the antioxidant effects. The biochemical analysis revealed that these compounds improve an abnormal level of several biochemical parameters like serum lipid values including total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C) to a normal level and the high-density lipoprotein cholesterol level (HDL-C). To understand the mechanism of action of ß-BA and ß-KBA, their most probable biological targets were searched through the inverse docking approach. Our computational analysis reflects that among other probable targets, the Dipeptidyl peptidase 4 (DPP-4) enzyme could be one of the possible binders of ß-BA and ß-KBA to produce their anti-diabetic activities. These in-silico results were validated by an in-vitro experiment. It indicates that the anti-diabetic effects of ß-BA and ß-KBA are produced by the inhibition of DDP-4. Thus, these anti-diabetic, antioxidant, and anti-hyperlipidemic effects of ß-BA and ß-KBA suggest these compounds as potential therapeutics for diabetic conditions.

Mitochondrial energy metabolism in baby hamster kidney (BHK-21/C13) cells treated with karnozin extra® / Metabolismo energético mitocondrial en células de riñón de hámster bebé (BHK-21 / C13) tratadas con karnozin extra®

SUMMARY: Carnosine is known as a natural dipeptide, which inhibits the proliferation of tumor cells throughout its action on mitochondrial respiration and cell glycolysis. However, not much is known about its effects on the metabolism of healthy cells. We explored the effects of Karnozin EXTRA® capsule with different concentrations of L-carnosine, on the cell viability and the expressions of intermediate filament vimentin (VIM) and superoxide dismutase (SOD2) in normal fibroblasts BHK-21/C13. Furthermore, we investigated its action on the energy production of these cells. Cell viability was quantified by the MTT assay. The Clark oxygen electrode (Oxygraph, Hansatech Instruments, England) was used to measure the "intact cell respiration rate", state 3 of ADP-stimulated oxidation, maximum oxidation capacity and the activities of complexes I, II and IV. Results showed that Karnozin EXTRA® capsule in concentrations of 2 and 5 mM of L-carnosine did not induce toxic effects and morphological changes in treated cells. Our data revealed a dose-dependent immunofluorescent signal amplification of VIM and SOD2 in the BHK-21/C13 cell line. This supplement substantially increased the recorded mitochondrial respiration rates in the examined cell line. Due to the stimulation of mitochondrial energy production in normal fibroblasts, our results suggested that Karnozin EXTRA® is a potentially protective dietary supplement in the prevention of diseases with altered mitochondrial function.

RESUMEN: La carnosina se conoce como dipéptido natural, que inhibe la proliferación de células tumorales a través de su acción sobre la respiración mitocondrial y la glucólisis celular. Sin embargo, no se sabe mucho de sus efectos sobre el metabolismo de las células sanas. Exploramos los efectos de la cápsula Karnozin EXTRA® con diferentes concentraciones de L-carnosina, sobre la viabilidad celular y las expresiones de vimentina de filamento intermedio (VIM) y superóxido dismutasa (SOD2) en fibroblastos normales BHK-21 / C13. Además, estudiamos su acción sobre la producción de energía de estas células. La viabilidad celular se cuantificó mediante el ensayo MTT. Se utilizó el electrodo de oxígeno Clark (Oxygraph, Hansatech Instruments, Inglaterra) para medir la "tasa de respiración de células intactas", el estado 3 de oxidación estimulada por ADP, la capacidad máxima de oxidación y las actividades de los complejos I, II y IV. Los resultados mostraron que la cápsula de Karnozin EXTRA® en concentraciones de 2 y 5 mM de L- carnosina no indujo efectos tóxicos ni cambios morfológicos en las células tratadas. Nuestros datos revelaron una amplificación de señal inmunofluorescente dependiente de la dosis de VIM y SOD2 en la línea celular BHK-21 / C13. Este suplemento aumentó sustancialmente las tasas de respiración mitocondrial registradas en la línea celular examinada. Debido a la estimulación de la producción de energía mitocondrial en fibroblastos normales, nuestros resultados sugirieron que Karnozin EXTRA® es un suplemento dietético potencialmente protector en la prevención de enfermedades con función mitocondrial alterada.

Protection from benzene-induced immune dysfunction in mice.

Benzene can impair peripheral immunity and immune organs; however, the recovery of benzene impairment has rarely been reported. In this study, we developed an immune dysfunction mouse model using a benzene gavage (500 mg/kg). Female Balb/c mice were treated with Bombyx batryticatus (BB, 5 g/kg), raw pinellia (RP, 5 g/kg), or a combination of Valproic acid and Coenzyme Q10 (CM, 150 mg/kg VPA & 100 mg/kg CoQ10) medication for four weeks. The immune function of the peripheral blood mononuclear cells (PBMCs), spleen, and thymus was determined to evaluate whether the observed impairment could be altered by medications in the mouse model. Results showed that medications could alleviate benzene-induced structural and functional damage of spleen and thymus. Benzene exposure decreased the ATP level of PBMC, which can be improved by BB, RP or CM. Importantly, BB, RP or CM could relieve benzene induced-oxidative stress by increasing the activities of glutathione peroxidase (GSH) and superoxide dismutase (SOD) and decreasing the contents of malondialdehyde (MDA). In conclusion, BB, RP, and CM were able to alleviate the benzene-induced immune dysfunction and redox imbalance. Improvement of the oxidative and antioxidant imbalance may represent a mechanism by which medicine prevents benzene-induced immune dysfunction.

Role of oxidative stress versus lipids in monocrotaline-induced pulmonary hypertension and right heart failure.

Pulmonary hypertension (PH) is a global health issue with a prevalence of 10% in ages >65 years. Right heart failure (RHF) is the main cause of death in PH. We have previously shown that monocrotaline (MCT)-induced PH and RHF are due to an increase in oxidative stress. In this study, probucol (PROB), a strong antioxidant with a lipid-lowering property, versus lovastatin (LOV), a strong lipid-lowering drug with some antioxidant effects, were evaluated for their effects on the MCT-induced RHF. Rats were treated (I.P.) with PROB (10 mg/kg ×12) or LOV (4 mg/kg ×12), daily 6 days before and 6 days after a single MCT injection (60 mg/kg). Serial echocardiography was performed and at 4-week post-MCT, lung wet-to-dry weight, hemodynamics, RV glutathione peroxidase (GSHPx), superoxide dismutase (SOD), catalase, lipid peroxidation, and myocardial as well as plasma lipids were examined. MCT increased RV systolic and diastolic pressures, wall thickness, RV end diastolic diameter, mortality, and decreased ejection fraction as well as pulmonary artery acceleration time. These changes were mitigated by PROB while LOV had no effect. Furthermore, PROB prevented lipid peroxidation, lowered lipids, and increased GSHPx and SOD in RV myocardium. LOV did decrease the lipids but had no effect on antioxidants and lipid peroxidation. A reduction in oxidative stress and not the lipid-lowering effect of PROB may explain the prevention of MCT-induced PH, RHF, and mortality. Thus targeting of oxidative stress as an adjuvant therapy is suggested.

Effect of Polygonatum odoratum ethanol extract on high glucose-induced tubular epithelial cell apoptosis and oxidative stress.

This work aims to analyze the effect of the ethanol extract from Polygonatum odoratum on high glucose-induced tubular epithelial cell apoptosis and oxidative stress. HK-2 injury of tubular epithelial cells was induced by high glucose, and the ethanol extract from Polygonatum odoratum was given. HK-2 cell activity and apoptosis were detected by MTT method and flow cytometry, respectively. Western blot was performed to analyze Cleaved-caspase3, Pro-caspase3, Nrf2, HO-1 protein expression. The levels of MDA, GSH, SOD were evaluated using commercial Kit. si-Nrf2 was transfected into HK-2 cells and high-glucose induction and ethanol extract from Polygonatum odoratum were given to observe the changes of cell apoptosis and oxidative stress. Ethanol extract from Polygonatum odoratum increased the high glucose-induced HK-2 cell activity, Pro-caspase3, Nrf2, HO-1 protein, GSH, SOD levels and decreased its apoptosis rate, Cleaved-caspase3 protein and MDA levels, showing statistically significant difference (p<0.05). After Nrf2 interference, high glucose-induced HK-2 cell activity, Pro-caspase3 protein, GSH, and SOD levels were decreased under the action of ethanol extract from Polygonatum odoratum, while the apoptosis rate, Cleaved-caspase3 protein, and MDA levels were increased significantly (p<0.05). The ethanol extract from Polygonatum odoratum can inhibit high glucose-induced tubular epithelial cell apoptosis and reduce oxidative stress by activating the Nrf2-ARE signaling pathway.

Evaluation of efficiency omega 3 fatty acid improves the behavioural phenotype and protects against oxidative stress against MPP+ induces Parkinson's disease in mice.

This experiment proposed to study the efficiency omega 3 fatty acid on behavioural phenotype of Parkinson's disease (PD) in mice. Totally 7 groups (each group 6 mice) were used in this assessment, each groups were treated with saline (control), MPP+, L-DOPA, Omega 3 oil, Omega 3 oil (three different concentrations) +MPP+ separately. The behavioral assessments such as bar test, open field test, maze test, hang test were noted on 7th, 14th, 21st and 28th day. After the examination period, the tested animals' midbrains and frontal cortex were dissected to analyze TBARS, GSH, Catalase, Superoxide Dismutase and Glutathione Peroxidase assay. In the bar test, 500mg omega 3 fatty acid administrated mice showed a high cataleptic scores. In open field Test, significant reductions in behavior analysis were observed from the tested mice group. Maze test and hang test doesn't show much difference. In biochemical test, tested groups showed promising results compared to control group. The result strongly proved that the omega 3 fatty acid has remarkable abilities to control the neurodegenerative diseases.

Protective role of salicylic acid in gentamicin induced nephrotoxicity.

Salicylic acid, a phenolic compound, found in plants, possesses free radical scavenging and iron chelation properties. The present study is designed to study the antioxidant effect of salicylic acid in gentamicin induced nephrotoxicity in rabbits. For this purpose twenty four male albino rabbits were divided into 4 groups (n=6); control group, healthy untreated rabbits, gentamicin group, received only gentamicin (80mg/kg), gentamicin + salicylic acid group, received gentamicin (80mg/kg) + salicylic acid (80mg/kg) and salicylic acid group, received only salicylic acid (80mg/kg) via intra peritoneal route for 21 consecutive days. Biochemical evaluation was carried out by assessment of body weights and by estimating renal function tests (plasma urea, plasma creatinine and plasma uric acid), tissue antioxidant enzymes (catalase, SOD) and MDA level. Gentamicin induction resulted in decreased body weights, increased plasma urea, plasma creatinine, plasma uric acid, tissue MDA level and decreased tissue SOD and tissue catalase activity in gentamicin treated group which was restored by supplementation with salicylic acid in gentamicin + salicylic acid group. Our data suggests that supplementation of salicylic acid can be useful in reducing gentamicin induced nephrotoxicity in rabbits.

Fenugreek seeds attenuate thioacetamide induced liver damage.

The intention to conduct this study was to evaluate the hepatoprotective effects of Fenugreek seeds' extract supplementation in thioacetamide induced liver damage in male Sprague Dawley rats. For this study, 24 male Sprague Dawley rats (200-264gm) were distributed randomly into four groups. Group I remained untreated as control rats, group II received thioacetamide (200mg/Kg b.w i.p, administered on alternative days for 8 weeks), group III received thioacetamide (200mg/Kg b.w i.p administered on alternative days for 8 weeks) as well as 2ml of 2% extract of fenugreek seeds (orally administered daily from 4th week till 8th week of the experiment. Group IV only received 2ml of 2% extract of Fenugreek seeds daily for 4 weeks respectively. At the end of the experiment, blood was sampled to obtain plasma that was used for the analysis of liver markers and liver was used for analysis of antioxidant enzymes (catalase and SOD). Increase in total bilirubin, direct bilirubin, ALT and ALP levels, catalase activity and decrease in SOD activity was found in TAA-treated groups which assured liver damage. Whereas, treatment with Fenugreek seeds extract restored the altered levels of total bilirubin, direct bilirubin, ALT, ALP, catalase and SOD activities in the Test + Supp group. The results of this study confirmed the hepatoprotective role of Fenugreek seeds extract in thioacetamide induced liver damage.

In vivo antioxidant potential of fruit mucilage from two varieties of Cucumis melo subsp. agrestis against oxidative stress induced toxicity.

To evaluate in-vivo antioxidant potential of fruit mucilage from Cucumis melo variety momordica (PM) and variety agrestis (KM) using rats as experimental animals, the fruits were collected, identified, dried and pulverized. Mucilages were isolated from the fruit powders by microwave-assisted method. Aqueous extracts obtained were filtered to remove fruit pulp. Each filtrate was centrifuged at 4000xg rpm for 15 min. Each supernatant was precipitated with 3 volumes of 95% ethanol and maintained overnight at 4°C. These precipitates were filtered and lyophilized. In vivo antioxidant activity was determined using rats for 14 days. Paracetamol (75mg/Kg, i.p.) for inducing oxidative stress and Vitamin C & Vitamin E (200mg/Kg each, p.o.) as standard treatment were used. PM and KM were given in 500mg/Kg and 1000mg/Kg, p.o. doses in separate groups. SOD, MDA, GSH and CAT levels were estimated in organs (liver, kidney, heart, brain) of all groups using standard procedures. Toxic control showed prominent toxicity in the liver. The levels of GSH, CAT and SOD were raised and MDA levels were reduced in all organs of test and standard groups. The levels of antioxidant biomarkers varied in all remaining groups. The overall results are significant suggesting strong antioxidant potential of PM and KM.

Increased endogenous reactive oxygen species normalizes proliferation defects of Bmi1 heterozygous knockout neural stem cells.

OBJECTIVES: The Bmi1gene, one of transcriptional suppressor genes in multi-comb family, maintains proliferation of neural stem cells (NSCs) and redox homeostasis. However, heterozygous deletion of the Bmi1 gene (Bmi1+/-) does not reduce the proliferative ability of NSCs. The aim of the present study was to reveal the underlying mechanism of this phenotype. METHODS: NSCs derived from the cortex of newborn Bmi1+/- and wild-type (WT) mice were treated with different concentrations of hydrogen peroxide (H2O2) and antioxidant N-acetyl-L-cysteine (NAC) for 24 h followed by analyses of NSC proliferation and oxidative stress-related indexes. RESULTS: The levels of reactive oxygen species (ROS) of Bmi1+/--NSCs were slightly higher than that of WT-NSCs at baseline. H2O2 increased ROS and NAC reduced ROS in a concentration-dependent pattern, but the change was significantly greater in Bmi1+/--NSCs than WT-NSCs. The proliferation and self-renewal ability of Bmi1+/--NSCs and WT-NSCs were comparable in a basic state. After 1 µM H2O2 treatment, Brdu incorporation ratio, cell viability, total antioxidant capacity (T-AOC) and total superoxide dismutase activity were increased slightly in WT-NSCs, but decreased in Bmi1+/--NSCs. H2O2 at 10 µM decreased proliferation and self-renewal ability of both genotype NSCs, with greater effect in Bmi1+/-. After treatment with 1 mM NAC, the number and diameter of neurospheres, Brdu incorporation rate, cell viability, T-AOC and total superoxide dismutase activity of Bmi1+/--NSCs were lower than those of WT-NSCs. CONCLUSION: These results suggest that Bmi1+/--NSCs exhibit normal proliferation and self-renewal due to a slight increase in ROS, but are more vulnerable to changes in redox status.

Effects of Zinc Acetate Hydrate Treatment on Serum Oxidative Stress Markers in Patients with Macular Drusen.

Purpose: To measure the serum levels of the oxidative stress markers superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GPx) and compare them before and after zinc supplementation in patients with early age-related macular degeneration (AMD). Methods: We measured serum zinc levels in 65 patients with early AMD. Of these, 29 patients with macular drusen and a serum zinc level <80 µg/dL received oral zinc acetate dihydrate (50 mg/day). Serum trace metal levels (zinc and copper) and oxidative stress marker levels (SOD, MDA, and GPx) were measured at baseline and 12 weeks after the treatment. The macular drusen areas and best-corrected visual acuity were evaluated in 24 participants who attended the 3-month follow-up. Results: MDA level was significantly decreased from baseline to 12 weeks after zinc administration (170.5 ± 100.9 vs. 148.3 ± 57.9 pmol/mL, P = 0.03), while SOD was significantly increased from baseline to 12 weeks after zinc intake (4.2 ± 0.9 vs. 4.6 ± 0.9 U/mL, P = 0.03). The serum zinc level was significantly correlated with the MDA level (P = 0.03, ρ = -0.26). The area of soft drusen was significantly decreased after zinc treatment (1,936,654.9 ± 1,348,267.6 vs. 966,883.9 ± 719,938.1 µmm2, P = 0.04). Conclusions: The levels of oxidative stress markers MDA and SOD decreased and increased, respectively, after oral zinc administration to 24 patients with AMD. The therapeutic effect of zinc treatment on drusen area might differ depending on the drusen phenotype in early AMD.

Regulation of Dendrobium Polysaccharides on Proliferation and Oxidative Stress of Human Umbilical Vein Endothelial Cells in the High Glucose Environment.

BACKGROUNDS: Polysaccharides of Dendrobium candidum (PDC) showed a strong antioxidant effect on islet cells while the effects of PDC on human umbilical vein endothelial cells (HUVECs) under the high glucose condition remain unclear. Material and Method. HUVECs were incubated with high glucose (33.3 mmol/L) for 48 hours to induce injury, and cells were treated with PDC (100, 200, and 400 µg/mL) for 48 hours. The tetrazolium blue colorimetric (MTT) assay was used to detect cell proliferation, superoxide dismutase (SOD), and nitric oxide (NO) content in cell supernatants. Flow cytometry was used to detect reactive oxygen species (ROS) and calcium levels. RESULTS: (1) Compared with the control group, the proliferation of HUVECs cells in the high glucose (33.3 mmol/L) group decreased (P < 0.05). The intracellular calcium ion concentration and the intracellular ROS level increased (P < 0.01 and P < 0.05). SOD activity and the level of NO in the culture medium were reduced (P <0.05). (2) Compared with the control group, PDC (50, 100, 200, 400, and 800 µg/mL) did not significantly affect the cell proliferation of HUVECs (P > 0.05). (3) Compared with the high glucose group, the HUVEC cell viability of the high glucose + PDC (100, 200, and 400 µg/mL) group increased while the intracellular calcium ion concentration decreased in a concentration-dependent manner (P < 0.05). Intracellular ROS levels were reduced, while SOD activity and the level of NO in culture fluids increased (P < 0.05). CONCLUSION: PDC can promote the proliferation of HUVECs in the high glucose environment by reducing oxidative stress injury of HUVECs induced by high glucose.