scholarly journals Mitochondrial Antioxidant SkQ1 Has a Beneficial Effect in Experimental Diabetes as Based on the Analysis of Expression of microRNAs and mRNAs for the Oxidative Metabolism Regulators

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1749
Author(s):  
Yuliya Dvoretskaya ◽  
Victor Glanz ◽  
Mariya Gryaznova ◽  
Mikhail Syromyatnikov ◽  
Vasily Popov
Keyword(s):  
Oxidative Stress ◽  
Free Radicals ◽  
Blood Glucose ◽  
Beneficial Effect ◽  
Experimental Diabetes ◽  
Quantitative Polymerase Chain Reaction ◽  
Expression Patterns ◽  
Mrna Levels ◽  
Glucose Content ◽  
Positive Effects

Diabetes mellitus and related complications are among the most important problems of the world-leading healthcare systems. Despite their priority, molecular and genetic aspects of diabetes pathogenesis are poorly understood; however, the involvement of oxidative stress in this process is undoubted. Rats with experimental diabetes induced by the intraperitoneal injection of alloxan were subjected to the antioxidant pre-therapy with a series of mitochondria-targeted 10-(6’-plastoquinonyl)decyltriphenylphosphonium (SkQ1) injections and analyzed for the expression of mRNAs and microRNAs by real-time quantitative polymerase chain reaction to identify potential predictors of diabetes. Animals that received SkQ1 before diabetes induction demonstrated lower blood glucose levels compared to the diabetic animals not subjected to the therapy. SkQ1 caused changes in the mRNA levels of genes involved in the cellular defense against free radicals, which indicates a beneficial effect of the pre-therapy. Moreover, similar changes were observed on the epigenetic level, as the microRNA expression patterns not only proved the SkQ1 efficacy but also correlated with the expression levels of their mRNA targets. Oxidative stress and macromolecule damage by free radicals are determining factors in diabetes, which suggests that strategies aimed at restoring the antioxidant status of the cell can be beneficial. Mitochondria-targeted antioxidant SkQ1 demonstrates positive effects on several levels, from the normalization of the blood glucose content to genetic and epigenetic changes. Our results can serve as a basis for the development of novel therapeutic and diagnostic strategies.

Gene and protein expression of connexins 37 and 43 in cumulus–oocytes complexes throughout the canine oestrous cycle

2020 ◽  
Vol 32 (11) ◽  
pp. 976
Author(s):  
Monica De los Reyes ◽  
Jaime Palomino ◽  
Carola Gallegos ◽  
Roberto Espinoza ◽  
Phillipe Dettleff ◽  
...  
Keyword(s):  
Quantitative Polymerase Chain Reaction ◽  
Expression Patterns ◽  
Cumulus Cells ◽  
Oestrous Cycle ◽  
Mrna Levels ◽  
Chain Reaction ◽  
Antral Follicles ◽  
Gene And Protein Expression ◽  
Before And After ◽  
Polymerase Chain

The aim of this study was to evaluate the expression of connexin (Cx) 37 and Cx43 in canine cumulus–oocyte complexes (COCs) during the oestrous cycle. Cx localisation was analysed by immunohistochemistry and immunofluorescence, whereas protein and gene expression was evaluated by western blotting and quantitative polymerase chain reaction respectively; comparisons were made using analysis of variance. Both Cx37 and Cx43 were expressed in all follicular stages; Cx43 was identified in cumulus cells and Cx37 was identified in cumulus cells, zonae pellucida and oocytes. Immunofluorescence analyses showed that Cx37 remained unchanged during the preovulatory stage but decreased after ovulation, whereas Cx43 remained unchanged before and after ovulation. Cx43 transcripts increased (P<0.05) during anoestrus and dioestrus in medium-sized follicles but remained unaltered during the pro-oestrus and antral stages during oestrus, before and after ovulation. Cx37 mRNA levels decreased in ovulated COCs (P<0.05). The highest levels of Cx37 protein (P<0.05) were detected in the preantral stage during anoestrus. In contrast, strong Cx43 signals were detected in oestrus and in medium-sized antral follicles in dioestrus (P<0.05). Overall, we demonstrated that Cx37 and Cx43 exhibit different expression patterns, suggesting specific roles throughout growth. Maintenance of Cx expression before ovulation indicates the involvement of Cx37 and Cx43 in the prolonged meiotic arrest.

scholarly journals Mice Deficient in Cyp4a14 Have An Increased Number of Goblet Cells and Attenuated Dextran Sulfate Sodium-Induced Colitis

2018 ◽  
Vol 50 (6) ◽  
pp. 2272-2282 ◽  
Author(s):  
Qingxia Xuan ◽  
Yunfeng Zhou ◽  
Binbin Tan ◽  
Zhongyue Xiao ◽  
Shizhen Dong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Quantitative Polymerase Chain Reaction ◽  
Periodic Acid ◽  
Mucosal Injury ◽  
Goblet Cells ◽  
Mrna Levels ◽  
Periodic Acid Schiff ◽  
Monooxygenase Activity

Background/Aims: Cyp4a14 is a member of cytochrome P450 (Cyp450) enzyme superfamily that possesses NADPH monooxygenase activity, which catalyzes omega-hydroxylation of medium-chain fatty acids and arachidonic acid. Study suggests that down-regulation of Cyp4a14 has an anti-inflammatory response in intestine. The present study was to test the function of Cyp4a14 in dextran sulfate sodium (DSS)-induced colitis. Methods: Female Cyp4a14-knockout (KO) and wild-type (WT) mice were treated with DSS for 6 days to induce colitis. The colon of mice was histologically observed by hematoxylin and eosin (H&E) and periodic acid Schiff (PAS) staining. The serum malondialdehyde (MDA), an endogenous indicator of oxidative stress, was chemically measured. Proinflammatory and NADPH oxidase genes were examined by quantitative polymerase chain reaction (qPCR). Results: Cyp4a14-KO mice had a significantly higher number of goblet cells in the colon and were more resistant to DSS-induced colitis compared with the WT mice. The DSS-treated KO mice had lower levels of MDA. Consistent with the milder inflammatory pathological changes, DSS-treated KO mice had lower levels of IL-1β, IL-6 and TNF-α mRNA in the liver and the colon. Moreover, the colon of DSS-treated Cyp4a14-KO and WT mice had higher mRNA levels of two members of NADPH oxidases, Nox2 and Nox4, suggesting that both Nox2 and Nox4 are inflammatory markers. By contrast, DSS-treated WT and KO mice had drastically decreased epithelium-localized Nox1 and dual oxidase (Duox) 2 mRNA levels, coinciding with the erosion of the mucosa induced by DSS. Conclusion: These results suggests a hypothesis that the increased goblet cell in the colon of Cyp4a14-KO mice provides protection from mucosal injury and Cyp4a14-increased oxidative stress exacerbates DSS-induced colitis. Therefore, Cyp4a14 may represent a potential target for treating colitis.

Molecular Characterization and Oxidative Stress Response of a Cytochrome P450 Gene (CYP4G11) from Apis cerana cerana

2013 ◽  
Vol 68 (11-12) ◽  
pp. 509-521 ◽  
Author(s):  
Weina Shi ◽  
Jing Sun ◽  
Baohua Xu ◽  
Han Li
Keyword(s):  
Oxidative Stress ◽  
Cytochrome P450 ◽  
Honey Bees ◽  
Uv Light ◽  
Quantitative Polymerase Chain Reaction ◽  
Expression Patterns ◽  
Apis Cerana ◽  
Apis Cerana Cerana ◽  
High Sequence Identity ◽  
P450 Gene

Cytochrome P450 proteins, widely distributed multifunctional enzymes, are mainly involved in biosynthetic and degradative pathways of endogenous compounds and the detoxification of xenobiotics in insects. Moreover, these enzymes exhibit peroxidase-like activity, therefore they may be involved in protecting organisms against the toxicity of reactive oxygen species (ROS). In the present study, we cloned a CYP4G11 gene - AccCYP4G11 - from the Chinese honey-bee (Apis cerana cerana). The open reading frame of the cDNA was 1656 bp long and encoded a 551 amino acids polypeptide, which shared high sequence identity with homologous cytochrome P450 proteins. In the genomic DNA sequence, a 5'-flanking region consisting of 1168 bp was obtained, and some putative transcription factor binding sites were predicted. Quantitative polymerase chain reaction (Q-PCR) revealed that the level of AccCYP4G11 was higher in the epidermis than in other tissues, and Acc- CYP4G11 was expressed in all stages with the highest level in two-week-old adult worker honey-bees. More over, the expression patterns under oxidative stress indicated that Acc- CYP4G11 transcription was significantly influenced by external factors, such as temperature challenges, ultraviolet (UV) light, and insecticide treatment. AccCYP4G11 was regulated differentially in response to oxidative stress and may be involved in protecting honey-bees from oxidative injury.

scholarly journals Zinc oxide nanoparticles improve testicular steroidogenesis machinery dysfunction in benzo[α]pyrene-challenged rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Niveen M. Daoud ◽  
Mohamed S. Aly ◽  
Omaima H. Ezzo ◽  
Naglaa A. Ali
Keyword(s):  
Oxidative Stress ◽  
Zinc Oxide ◽  
Zinc Oxide Nanoparticles ◽  
Molecular Mechanisms ◽  
Regulatory Protein ◽  
Male Rats ◽  
Oxide Nanoparticles ◽  
Mrna Levels ◽  
Zno Nps ◽  
Positive Effects

AbstractZinc oxide nanoparticles (ZnO NPs) demonstrate potential positive effects on reproduction. However, their protective role against the reproductive toxicity pollutants has not yet been adequately studied at the molecular level. This study was designed to assess this objective using Benzo[α]pyrene B[a]P as reproductive toxic agent . Forty-eight mature male rats were randomly distributed into six groups: Group1 (negative control); Groups 2 and 3 (positive control I and II, wherein the animals were treated with 10 and 30 mg ZnO NPs/kg BW, respectively); Group 4 (B[a]P group; treated with 150 mg B[a]P/kg BW); and Groups 5 and 6 (subjected to B[a]P treatment co-administered with different concentrations of ZnO NPs). We investigated oxidative stress biomarkers; cholesterol side-chain cleavage enzyme (CYP11A1), steroidogenic acute regulatory protein (StAR), and 3β-hydroxysteroid dehydrogenase (3β-HSD) gene expression; testosterone levels; and histopathology of the liver, kidney, and testicles. The B[a]P-treated group showed significant deterioration in all reproductive parameters and displayed induced oxidative stress. ZnO NPs remarkably reduced oxidative stress, effectively upregulated the mRNA levels of CY11A1, StAR, and 3β-HSD, and improved the histological pictures in the examined organs. At their investigated doses and given their NPs properties, ZnO NPs demonstrated a marked ameliorative effect against the reproductive toxic effects of B[a]P. Further studies are needed to thoroughly investigate the molecular mechanisms of ZnO NPs.

scholarly journals Simvastatin Protects Dopaminergic Neurons Against MPP+-Induced Oxidative Stress and Regulates the Endogenous Anti-Oxidant System Through ERK

2018 ◽  
Vol 51 (4) ◽  
pp. 1957-1968 ◽  
Author(s):  
Junqiang Yan ◽  
Liang Qiao ◽  
Jiannan Wu ◽  
Hua Fan ◽  
Jiachun Sun ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Substantia Nigra ◽  
Culture Media ◽  
Cell Model ◽  
Neuroprotective Effect ◽  
Condensation Reaction ◽  
Quantitative Polymerase Chain Reaction ◽  
Heme Oxygenase 1 ◽  
Mrna Levels ◽  
Anti Oxidant

Background/Aims: Many clinical studies have demonstrated that statins, especially simvastatin, can decrease the incidence of Parkinson’s disease (PD). However, the specific underlying mechanism remains unclear. This study aimed to investigate how simvastatin affects experimental parkinsonian models via the regulation of extracellular signal-regulated kinase 1/2 (ERK1/2)-mediated activation of the anti-oxidant system. Methods: l-Methyl-4-phenylpyridine ion (MPP+)-treated SH-SY5Y cells and substantia nigra neurons were used to investigate the neuroprotective effect of simvastatin. After incubation with MPP+ and/or simvastatin for 24 h, the MTT assay was used to assess cell viability. Reactive oxygen species (ROS) levels were measured using 2′,7′-dichlorofluorescin diacetate, while cellular superoxide dismutase (SOD) levels were determined based on the blue formazan produced by the reduction of nitroblue tetrazolium. The level of cellular grade micro-reduced glutathione (GSH) was measured with 5,5’-dithiobis-(2-nitrobenzoic acid). Meanwhile, the malondialdehyde content released from SH-SY5Y cells and substantia nigra neuronal cells exposed to different culture media was calculated based on the condensation reaction involving thiobarbituric acid. The mRNA levels of genes encoding nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase 1 (HO-1), and NAD(P)H dehydrogenase (quinone) 1 (NQO-1) were determined by a quantitative polymerase chain reaction assay, while the ERK, Nrf2, HO-1, NOX2, and NQO-1 protein levels were analyzed by western blot. Additionally, ERK small interfering RNA (siRNA) was used to investigate the mechanisms underlying MPP+-induced oxidative stress and the regulation of the endogenous anti-oxidant system. Results: Simvastatin (1.5 μM) enhanced the viability of SH-SY5Y cells and primary neurons treated with MPP+, and significantly alleviated the oxidative stress induced by MPP+ in SH-SY5Y cells by regulating the production of SOD, analytical grade micro-reduced GSH, and ROS, which may be associated with the activation of the Nrf2 anti-oxidant system. An analysis involving ERK1/2 siRNA revealed that simvastatin can inhibit NOX2 expression via the activation of ERK1/2 in the MPP+-treated PD cell model. Conclusion: Our results provide strong evidence that ERK1/2-mediated modulation of the anti-oxidant system after simvastatin treatment may partially explain the anti-oxidant activity in experimental parkinsonian models. These findings contribute to a better understanding of the critical roles of simvastatin via the ERK1/2-mediated modulation of the anti-oxidant system, which may be relevant for treating PD.

Copper-dependent ATP7B up-regulation drives the resistance of TMEM16A-overexpressing head-and-neck cancer models to platinum toxicity

2019 ◽  
Vol 476 (24) ◽  
pp. 3705-3719 ◽  
Author(s):  
Avani Vyas ◽  
Umamaheswar Duvvuri ◽  
Kirill Kiselyov
Keyword(s):  
Oxidative Stress ◽  
Head And Neck ◽  
Transcriptional Activation ◽  
Platinum Resistance ◽  
Mrna Levels ◽  
Strong Positive Correlation ◽  
Platinum Compounds ◽  
Copper Chelation ◽  
Novel Approach ◽  
Cancer Models

Platinum-containing drugs such as cisplatin and carboplatin are routinely used for the treatment of many solid tumors including squamous cell carcinoma of the head and neck (SCCHN). However, SCCHN resistance to platinum compounds is well documented. The resistance to platinum has been linked to the activity of divalent transporter ATP7B, which pumps platinum from the cytoplasm into lysosomes, decreasing its concentration in the cytoplasm. Several cancer models show increased expression of ATP7B; however, the reason for such an increase is not known. Here we show a strong positive correlation between mRNA levels of TMEM16A and ATP7B in human SCCHN tumors. TMEM16A overexpression and depletion in SCCHN cell lines caused parallel changes in the ATP7B mRNA levels. The ATP7B increase in TMEM16A-overexpressing cells was reversed by suppression of NADPH oxidase 2 (NOX2), by the antioxidant N-Acetyl-Cysteine (NAC) and by copper chelation using cuprizone and bathocuproine sulphonate (BCS). Pretreatment with either chelator significantly increased cisplatin's sensitivity, particularly in the context of TMEM16A overexpression. We propose that increased oxidative stress in TMEM16A-overexpressing cells liberates the chelated copper in the cytoplasm, leading to the transcriptional activation of ATP7B expression. This, in turn, decreases the efficacy of platinum compounds by promoting their vesicular sequestration. We think that such a new explanation of the mechanism of SCCHN tumors’ platinum resistance identifies novel approach to treating these tumors.

UJI AKTIVITAS ANTIOKSIDAN FRAKSI N-HEKSAN DAUN AFRIKA (Vernonia amygdalina Del.) DENGAN METODE DPPH

2020 ◽  
Vol 5 (2) ◽  
pp. 250-257
Author(s):  
Nurul Fatimah ◽  
◽  
Reksi Sundu
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Free Radicals ◽  
Ethanolic Extract ◽  
Ethanol Extract ◽  
Hexane Fraction ◽  
Phytochemical Screening ◽  
Vernonia Amygdalina ◽  
Tropical Africa ◽  
Ic50 Value

Free radicals and reactive species are widely believed to contribute to the development of several diseases by causing oxidative stress and eventually oxidative. Vernonia amygdalina (Astereacea) is a small shrub or tree between 1 and 5m high growing throughout tropical Africa. Plants are generally known as bitter leaves is well cultivated and is a general market for merchandise in several countries. The purpose of this study was to determine the antioxidant activity of hexane fraction from ethanol extract od Frican leaves (Vernonia amygdalina Del.). The method used in this study was the DPPH (1,1-Diphenil-2-Picrylhydrazyl) method. The result of phytochemical screening showed that ethanolic extract of African leaves contained a composition of secondary metabolites of alkaloids, flavonoids, tannins, steroids/triterpenoids and saponins. The antioxidant activity of the extract of n-hexane fraction was classified as very weak with an IC50 value of 317.98 ppm.

Evaluation of Salivary Antioxidants and Oxidative Stress Markers in Male Smokers

2019 ◽  
Vol 22 (7) ◽  
pp. 496-501
Author(s):  
Fatemeh Ahmadi-Motamayel ◽  
Parisa Falsafi ◽  
Hamidreza Abolsamadi ◽  
Mohammad T. Goodarzi ◽  
Jalal Poorolajal
Keyword(s):  
Oxidative Stress ◽  
Uric Acid ◽  
Free Radicals ◽  
Antioxidant Capacity ◽  
Cigarette Smoke ◽  
Total Antioxidant Capacity ◽  
The Body ◽  
Total Antioxidant ◽  
The Mean ◽  
And Oxidative Stress

Background: Cigarette smoke free radicals can cause cellular damage and different diseases. All the body fluids have antioxidants which protect against free radicals. Objective: The aim of this study was to evaluate salivary total antioxidant capacity and peroxidase, uric acid and malondialdehyde levels in smokers and a nonsmoking control group. Methods: Unstimulated saliva was collected from 510 males. A total of 259 subjects were current smokers and 251 were non-smokers. The levels of salivary total antioxidant capacity, uric acid, peroxidase and malondialdehyde were measured using standard procedures. Data were analyzed with t test and ANOVA. Results: The smokers were younger and dental hygiene index was higher than healthy nonsmoking controls. The mean total antioxidant capacity in smokers and nonsmokers was 0.13±0.07 and 0.21±011, respectively (P=0.001). Smokers had significantly lower peroxidase and uric acid levels than healthy controls. In addition, the mean malondialdehyde levels in the smokers and nonsmokers were 4.55 ±2.61 and 2.79 ±2.21, respectively (P=0.001). Conclusion: Cigarette smoke produces free radical and oxidative stress, causing many side effects. Salivary antioxidant levels decreased and malondialdehyde levels increased in smokers, indicating the high oxidative stress among smokers compared to nonsmokers. Cigarette smoke had deleterious effects on main salivary antioxidants levels.

Exercise and Stevia Rebaudiana (R) Extracts Attenuate Diabetic Cardiomyopathy in Type 2 Diabetic Rats: Possible Underlying Mechanisms

2020 ◽  
Vol 20 (7) ◽  
pp. 1117-1132
Author(s):  
Abdelaziz M. Hussein ◽  
Elsayed A. Eid ◽  
Ismaeel Bin-Jaliah ◽  
Medhat Taha ◽  
Lashin S. Lashin
Keyword(s):  
Oxidative Stress ◽  
Blood Glucose ◽  
Diabetic Cardiomyopathy ◽  
Caspase 3 ◽  
Stevia Rebaudiana ◽  
Diabetic Rats ◽  
Control Group ◽  
Underlying Mechanisms ◽  
Type 2 Diabetic

Background and Aims: In the current work, we studied the effects of exercise and stevia rebaudiana (R) extracts on diabetic cardiomyopathy (DCM) in type 2 diabetic rats and their possible underlying mechanisms. Methods: : Thirty-two male Sprague Dawley rats were randomly allocated into 4 equal groups; a) normal control group, b) DM group, type 2 diabetic rats received 2 ml oral saline daily for 4 weeks, c) DM+ Exercise, type 2 diabetic rats were treated with exercise for 4 weeks and d) DM+ stevia R extracts: type 2 diabetic rats received methanolic stevia R extracts. By the end of the experiment, serum blood glucose, HOMA-IR, insulin and cardiac enzymes (LDH, CK-MB), cardiac histopathology, oxidative stress markers (MDA, GSH and CAT), myocardial fibrosis by Masson trichrome, the expression of p53, caspase-3, α-SMA and tyrosine hydroxylase (TH) by immunostaining in myocardial tissues were measured. Results: T2DM caused a significant increase in blood glucose, HOMA-IR index, serum CK-MB and LDH, myocardial damage and fibrosis, myocardial MDA, myocardial α-SMA, p53, caspase-3, Nrf2 and TH density with a significant decrease in serum insulin and myocardial GSH and CAT (p< 0.05). On the other hand, treatment with either exercise or stevia R extracts significantly improved all studied parameters (p< 0.05). Moreover, the effects of stevia R was more significant than exercise (p< 0.05). Conclusion: Both exercise and methanolic stevia R extracts showed cardioprotective effects against DCM and Stevia R offered more cardioprotective than exercise. This cardioprotective effect of these lines of treatment might be due to attenuation of oxidative stress, apoptosis, sympathetic nerve density and fibrosis and upregulation of the antioxidant transcription factor, Nrf2.

Theaflavin Enriched Black Tea Extract Alleviates Diabetic Nephropathy by Suppressing Hyperglycaemia-Mediated Oxidative Stress and Inflammation in Streptozotocin-Induced Rats

2020 ◽  
Vol 10 ◽  
Author(s):  
Dhrubajyoti Sarkar ◽  
Sekhar Kumar Bose ◽  
Tania Chakraborty ◽  
Souvik Roy
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Blood Glucose ◽  
Blood Urea Nitrogen ◽  
Phenolic Content ◽  
Black Tea ◽  
Total Phenolic ◽  
Urea Nitrogen ◽  
Black Tea Extract ◽  
Tea Extract

Background: Diabetic nephropathy (DN), a microvascular complication of diabetes has been a significant health issue globally. However, theaflavin enriched black tea extract (BTE-TF) could restrain DN. Objective: The main objective of this exploration was to elucidate the effect of BTE-TF on DN, though the underlying mechanism remains unclear and requires further investigation. Method: The tea leaves were fermented to get black tea extract. Total phenolic content and HPLC were carried out to determine the phenolic content and theaflavin in the extract. Streptozotocin induced diabetic rats were treated with 100, 200, and 400 mg/kg/day BTE-TF extract for 12 weeks. Biochemical parameters like blood glucose, creatinine, blood urea nitrogen (BUN), triglyceride and antioxidant parameters of kidney tissue were measured. Histology, immunohistochemistry and TUNEL assay were performed to observe the effect of the extract with comparison to the standard drug (Metformin 200mg/kg/day). Result: Treated animals exhibited reduced blood glucose levels, blood urea nitrogen (BUN), creatinine, and serum triglycerides. Further, BTE-TF restored the histological alterations in the kidney. Chronic hyperglycaemia resulted in a significant increase in oxidative stress and pro-inflammatory cytokines of NF-kβ pathway. BTE-TF attenuated oxidative stress (p<0.01), inflammation (p<0.05) and apoptosis (p<0.05). Conclusion: This study suggests that BTE-TF exerts a protective role against diabetes-induced renal injury by ameliorating oxidative stress, inflammation, and apoptosis.

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