scholarly journals Salvianolate Protects Hepatocytes from Oxidative Stress by Attenuating Mitochondrial Injury

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Qiang Zhao ◽  
Yuan Peng ◽  
Kai Huang ◽  
Yang Lei ◽  
Hong-Liang Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Function ◽  
Mouse Liver ◽  
Hepatic Injury ◽  
Transmission Electron ◽  
Male Wistar Rats ◽  
Hematoxylin And Eosin ◽  
Mitotracker Green

Salvianolate is widely used to treat angiocardiopathy in clinic in China, but its application in liver diseases remains unclear. Our study aims to investigate the effect of Salvianolate on rat hepatic injury by protecting hepatocyte mitochondria. To evaluate the effects of Salvianolate on injured hepatocytes, alpha mouse liver 12 (AML-12) cells were induced with hydrogen peroxide (H2O2) and treated with Salvianolate. Cell viability and MitoTracker Green for mitochondria and 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazole-carbocyanide iodine (JC-1) levels and cytochrome C (Cyto-C) expressions were detectedin vitro. To identify the effect of Salvianolate on protecting against mitochondria injury, male Wistar rats were injected with carbon tetrachloride (CCl4) and treated with Salvianolate (40 mg·kg−1). Serum liver function, parameters for peroxidative damage, hematoxylin and eosin (H&E) staining, and transmission electron microscope (TEM) of hepatocyte mitochondria were assayed. Our results showed that Salvianolate effectively protected hepatocytes, increased mitochondria vitality, and decreased Cyto-C expressionsin vitro. Besides, Salvianolate alleviated the liver function, attenuated the indicators of peroxidation, and relieved the mitochondria injuryin vivo. In conclusion,Salvianolateis effective in protecting hepatocytes from injuryin vitroandin vivo, and the mechanism might be related to its protective effect on hepatocyte mitochondria against oxidative stress.

Oxidative stress in primary culture hepatocytes isolated from partially hepatectomized rats

2007 ◽  
Vol 85 (10) ◽  
pp. 1047-1051 ◽  
Author(s):  
Daniel Francés ◽  
M. Teresa Ronco ◽  
Elena Ochoa ◽  
M. Luján Alvarez ◽  
Ariel Quiroga ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Primary Culture ◽  
Cell Injury ◽  
Cultured Cells ◽  
Male Wistar Rats ◽  
Metabolic Activities ◽  
Stress Oxidative ◽  
Species Production

The aim of this study was to evaluate the influence of partial hepatectomy prior to cell isolation on hepatocytes in vitro. We characterized the possible changes of various stress oxidative parameters within the first 24 h after seeding. Male Wistar rats served as donors. Hepatocytes were isolated by collagenase digestion from either liver of simulated surgery (SH) or from liver 1 h after 70% hepatectomy (PH), and the changes in stress parameters were analyzed after 1, 3, 18, and 24 h in culture. At 24 h, only hepatocytes from PH maintained significantly increased reactive oxygen species production, oxidized glutathione percentage, and Cu/Zn superoxide dismutase and catalase activities. Our results show that hepatocytes suffer significant cell injury as a result of the isolation procedure, but primary cultured cells from SH metabolically recover from this stress after 18 h. After this time, primary culture hepatocytes primed by PH maintain their in vivo-like metabolic activities (increase in both oxidative stress and antioxidant status).

scholarly journals The protective effect of klotho against contrast-associated acute kidney injury via the antioxidative effect

2019 ◽  
Vol 317 (4) ◽  
pp. F881-F889 ◽  
Author(s):  
Hyung Jung Oh ◽  
Hyewon Oh ◽  
Bo Young Nam ◽  
Je Sung You ◽  
Dong-Ryeol Ryu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Kidney Injury ◽  
Antioxidative Effect ◽  
In Vivo Experiments ◽  
Apoptotic Markers ◽  
Cytoplasmic Vacuoles ◽  
Transmission Electron ◽  
And Oxidative Stress

As oxidative stress is one major factor behind contrast-associated acute kidney injury (CA-AKI), we investigated the protective effect of klotho against CA-AKI via the antioxidative effect. In in vitro experiments, cells (NRK-52E) were divided into the following three groups: control, iopamidol, or iopamidol + recombinant klotho (rKL) groups. Moreover, cell viability was measured with the Cell Counting Kit-8 assay, and oxidative stress was examined with 2',7'-dichlorodihydrofluorescein diacetate fluorescence intensity. RT-PCR and Western blot analysis were performed to assess propidium iodide klotho expression, and Bax-to-Bcl-2 and apoptosis ratios were evaluated with annexin V/Hoechst 33342 staining. Furthermore, we knocked down the klotho gene using siRNA to verify the endogenous effect of klotho. In our in vivo experiments, oxidative stress was evaluated with the thiobarbituric acid-reactive substance assay, and apoptosis was evaluated with the Bax-to-Bcl-2 ratio and cleaved caspase-3 immunohistochemistry. Additionally, cell and tissue morphology were investigated with transmission electron microscopy. In both in vitro and in vivo experiments, mRNA and protein expression of klotho significantly decreased in CA-AKI mice compared with control mice, whereas oxidative stress and apoptosis markers were significantly increased in CA-AKI mice. However, rKL supplementation mitigated the elevated apoptotic markers and oxidative stress in the CA-AKI mouse model and improved cell viability. In contrast, oxidative stress and apoptotic markers were more aggravated when the klotho gene was knocked down. Moreover, we found more cytoplasmic vacuoles in the CA-AKI mouse model using transmission electron microscopy but fewer cytoplasmic vacuoles in rKL-supplemented cells. The present study shows that klotho in proximal tubular cells can protect against CA-AKI via an antioxidative effect.

scholarly journals Hepatoprotective Actions of Ascorbic Acid, Alpha Lipoic Acid and Silymarin or Their Combination Against Acetaminophen-Induced Hepatotoxicity in Rats

Medicina ◽  
2019 ◽  
Vol 55 (5) ◽  
pp. 181 ◽  
Author(s):  
Anmar M. Abdulrazzaq ◽  
Mujtaba Badr ◽  
Omar Gammoh ◽  
Asad A. Abu Khalil ◽  
Bayan Y. Ghanim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ascorbic Acid ◽  
Liver Function ◽  
Lipoic Acid ◽  
Rat Hepatocytes ◽  
Serum Levels ◽  
Liver Function Tests ◽  
Alpha Lipoic Acid

Background and objectives: Ascorbic acid, alpha lipoic acid (ALA) and silymarin are well-known antioxidants that have hepatoprotective effects. This study aims to investigate the effects of these three compounds combined with attenuating drug-induced oxidative stress and cellular damage, taking acetaminophen (APAP)-induced toxicity in rats as a model both in vivo and in vitro. Materials and Methods: Freshly cultured primary rat hepatocytes were treated with ascorbic acid, ALA, silymarin and their combination, both with and without the addition of APAP to evaluate their in vitro impact on cell proliferation and mitochondrial activity. In vivo study was performed on rats supplemented with the test compounds or their combination for one week followed by two toxic doses of APAP. Results: Selected liver function tests and oxidative stress markers including superoxide dismutase (SOD), malondialdehyde (MDA) and oxidized glutathione (GSSG) were detected. The in vivo results showed that all three pretreatment compounds and their combination prevented elevation of SOD and GSSG serum levels indicating a diminished burden of oxidative stress. Moreover, ascorbic acid, ALA and silymarin in combination reduced serum levels of liver enzymes; however, silymarin markedly maintained levels of all parameters to normal ranges. Silymarin either alone or combined with ascorbic acid and ALA protected cultured rat hepatocytes and increased cellular metabolic activity. The subjected agents were capable of significantly inhibiting the presence of oxidative stress induced by APAP toxicity and the best result for protection was seen with the use of silymarin. Conclusions: The measured liver function tests may suggest an augmented hepatoprotection of the combination preparation than when compared individually.

scholarly journals Protection against Oxidative Stress-induced Hepatic Injury by Intracellular Type II Platelet-activating Factor Acetylhydrolase by Metabolism of Oxidized Phospholipids in Vivo

2007 ◽  
Vol 283 (3) ◽  
pp. 1628-1636 ◽  
Author(s):  
Nozomu Kono ◽  
Takao Inoue ◽  
Yasukazu Yoshida ◽  
Hiroyuki Sato ◽  
Tomokazu Matsusue ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hepatic Injury ◽  
Platelet Activating Factor ◽  
Type Ii ◽  
Oxidized Phospholipids ◽  
Wild Type ◽  
Membrane Phospholipids ◽  
Platelet Activating Factor Acetylhydrolase

Membrane phospholipids are susceptible to oxidation, which is involved in various pathological processes such as inflammation, atherogenesis, neurodegeneration, and aging. One enzyme that may help to remove oxidized phospholipids from cells is intracellular type II platelet-activating factor acetylhydrolase (PAF-AH (II)), which hydrolyzes oxidatively fragmented fatty acyl chains attached to phospholipids. Overexpression of PAF-AH (II) in cells or tissues was previously shown to suppress oxidative stress-induced cell death. In this study we investigated the functions of PAF-AH (II) by generating PAF-AH (II)-deficient (Pafah2-/-) mice. PAF-AH (II) was predominantly expressed in epithelial cells such as kidney proximal and distal tubules, intestinal column epithelium, and hepatocytes. Although PAF-AH activity was almost abolished in the liver and kidney of Pafah2-/- mice, Pafah2-/- mice developed normally and were phenotypically indistinguishable from wild-type mice. However, mouse embryonic fibroblasts derived from Pafah2-/- mice were more sensitive to tert-butylhydroperoxide treatment than those derived from wild-type mice. When carbon tetrachloride (CCl4) was injected into mice, Pafah2-/- mice showed a delay in hepatic injury recovery. Moreover, after CCl4 administration, liver levels of the esterified form of 8-iso-PGF2α, a known in vitro substrate of PAF-AH (II), were higher in Pafah2-/- mice than in wild-type mice. These results indicate that PAF-AH (II) is involved in the metabolism of esterified 8-isoprostaglandin F2α and protects tissue from oxidative stress-induced injury.

The Different Genotoxicity of P-Dichlorobenzene in Mouse and Rat: Measurement of the in Vivo and in Vitro Covalent Interaction with Nucleic Acids

1989 ◽  
Vol 75 (4) ◽  
pp. 305-310 ◽  
Author(s):  
Giovanna Lattanzi ◽  
Silvana Bartoli ◽  
Bruna Bonora ◽  
Annamaria Colacci ◽  
Sandro Grilli ◽  
...  
Keyword(s):  
Mouse Liver ◽  
Covalent Binding ◽  
Minor Role ◽  
Covalent Interaction ◽  
Male Wistar Rats ◽  
Mixed Function Oxidase System ◽  
Index Value ◽  
A Minor

Twenty-two hours after i.p. injection to male Wistar rats and BALB/c mice para-dichlorobenzene (p-DCB) is bound covalently to DNA from liver, kidney, lung and stomach of mice but not of rats. DNA adducts in mouse liver are repaired in seventy-two hours. The covalent binding index value, calculated on the labelling of mouse liver DNA, classifies p-DCB as a weak initiator with an oncogenic activity lower than that of chlorobenzene. The labelling of RNA and proteins from the different organs of both species is, however, low. In vitro interaction with calf thymus DNA mediated by mouse and rat microsomes from liver and lung did occur. Binding extent was strongly reduced by addition of 2-diethylaminoethyl-2,2-diphenylvalerate hydrochloride (SKF 525-A) to the microsomal standard incubation mixture, whereas it was enhanced by adding GSH. Cytosolic fractions from kidney and lung were able to induce binding of p-DCB to DNA to a lower extent with respect to microsome-mediated binding. These results indicate that microsomal mixed function oxidase system and microsomal GSH-transferases can be involved in overall activating metabolism whereas cytosolic GSH-transferases play a minor role. This study, which is a part of a structure-activity relationship approach on benzene and its haloderivatives, provides the first evidence of genotoxicity of p-DCB in mammalian cell. It allows to partly explain variations of susceptibility of different species to hepatocarcinogenesis and of hepatotoxicity of different isomers.

scholarly journals Berberine Improved Aldo-Induced Podocyte Injury via Inhibiting Oxidative Stress and Endoplasmic Reticulum Stress Pathways both In Vivo and In Vitro

2016 ◽  
Vol 39 (1) ◽  
pp. 217-228 ◽  
Author(s):  
Bin Wang ◽  
Xianlin Xu ◽  
Xiaozhou He ◽  
Zhigang Wang ◽  
Min Yang
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Annexin V ◽  
Isoquinoline Alkaloid ◽  
Sprague Dawley ◽  
Podocyte Injury ◽  
Transmission Electron

Background/Aims: Berberine, a naturally occurring isoquinoline alkaloid, acts against oxidative stress (OS) and endoplasmic reticulum stress (ERS), both of which are responsible for Aldosterone (Aldo) -induced podocyte injury. However, the direct effects of berberine on Aldo-induced OS, ERS, and podocyte injury are not well defined. Methods: Uninephrectomized Sprague-Dawley rats were given 1% NaCl (salt) in their water and an Aldo infusion (0.75 µg/h) for 28 days to induce podocyte injury in the Aldo group. In the Aldo/berberine group, in addition to Aldo infusion, rats were administered 150 mg/kg berberine per day by gastric gavage for 4 weeks. Podocytes were incubated in media containing either buffer or Aldo in the presence or absence of berberine for variable time periods. The kidney tissues and podocytes were then investigated using morphological analysis, immunohistochemistry, transmission electron microscopy, western blot, DHE staining, DCFDA fluorescence, and Annexin V staining. Results: Here, we have reported that berberine attenuated Aldo-induced OS, ERS, and podocyte injury both in vivo and in vitro. Additionally, berberine treatment improved the extensive fusion of foot processes in electron micrographs resulting from Aldo/salt infusion in rats. Conclusion: Berberine may be examined as an effective agent against Aldo-induced podocyte injury.

scholarly journals Metformin and Probiotics Interplay in Amelioration of Ethanol-Induced Oxidative Stress and Inflammatory Response in an In Vitro and In Vivo Model of Hepatic Injury

2021 ◽  
Vol 2021 ◽  
pp. 1-31
Author(s):  
Farhin Patel ◽  
Kirti Parwani ◽  
Dhara Patel ◽  
Palash Mandal
Keyword(s):  
Oxidative Stress ◽  
Lipid Metabolism ◽  
Liver Injury ◽  
Inflammatory Response ◽  
Er Stress ◽  
Hepg2 Cells ◽  
Hepatic Injury ◽  
And Oxidative Stress

Alcohol-induced liver injury implicates inflammation and oxidative stress as important mediators. Despite rigorous research, there is still no Food and Drug Administration (FDA) approved therapies for any stage of alcoholic liver disease (ALD). Interestingly, metformin (Met) and several probiotic strains possess the potential of inhibiting alcoholic liver injury. Therefore, we investigated the effectiveness of combination therapy using a mixture of eight strains of lactic acid-producing bacteria, commercialized as Visbiome® (V) and Met in preventing the ethanol-induced hepatic injury using in vitro and in vivo models. Human HepG2 cells and male Wistar rats were exposed to ethanol and simultaneously treated with probiotic V or Met alone as well as in combination. Endoplasmic reticulum (ER) stress markers, inflammatory markers, lipid metabolism, reactive oxygen species (ROS) production, and oxidative stress were evaluated, using qRT-PCR, Oil red O staining, fluorimetry, and HPLC. In vitro, probiotic V and Met in combination prevented ethanol-induced cellular injury, ER stress, oxidative stress, and regulated lipid metabolism as well as inflammatory response in HepG2 cells. Probiotic V and Met also promoted macrophage polarization towards the M2 phenotype in ethanol-exposed RAW 264.7 macrophage cells. In vivo, combined administration of probiotic V and Met ameliorated the histopathological changes, inflammatory response, hepatic markers (liver enzymes), and lipid metabolism induced by ethanol. It also improved the antioxidant markers (HO-1 and Nrf-2), as seen by their protein levels in both HepG2 cells as well as liver tissue using ELISA. Hence, probiotic V may act, in addition to the Met, as an effective preventive treatment against ethanol-induced hepatic injury.

scholarly journals Protective Effect of Methylxanthine Fractions Isolated from Bancha Tea Leaves against Doxorubicin-Induced Cardio- and Nephrotoxicities in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Maya P. Radeva-Ilieva ◽  
Kaloyan D. Georgiev ◽  
Nadezhda R. Hvarchanova ◽  
Stanila S. Stoeva ◽  
Iliya J. Slavov ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Tissue Damage ◽  
Histological Analysis ◽  
Concomitant Administration ◽  
Renal Tissue ◽  
Creatinine Kinase ◽  
Male Wistar Rats

Doxorubicin is an anthracycline antibiotic that is used for the treatment of various types of cancer. However, its clinical usage is limited due to its potential life-threatening adverse effects, such as cardio- and nephrotoxicities. Nonetheless, simultaneous administration of doxorubicin and antioxidants, such as those found in green tea leaves, could reduce cardiac and renal tissue damage caused by oxidative stress. The methylxanthine fraction isolated from Bancha tea leaves were tested in vitro for its antioxidant activity and in vivo for its organoprotective properties against doxorubicin-induced cardio- and nephrotoxicities in a rat model. The in vivo study was conducted on male Wistar rats divided into 6 groups. Methylxanthines were administered at high (5 mg/kg body weight) and low (1 mg/kg body weight) doses, while doxorubicin was administered at a cumulative dose of 20 mg/kg body weight. Serum creatinine, uric acid, and urea concentrations, as well as serum enzyme levels (creatinine kinase (CK), creatinine kinase MB fraction (CK-MB), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH)) and electrolytes (Na+, K+, and Cl-), were analysed. In addition, histological analysis was performed to assess cardiac and renal tissue damage. The concomitant administration of Bancha methylxanthines and doxorubicin showed a dose-dependent reduction in the serum biochemical parameters, indicating a decrease in the cardiac and renal tissue damage caused by the antibiotic. Histological analysis showed that pretreatment with methylxanthines at the dose of 5 mg/kg resulted in an almost normal myocardial structure and a significant decrease in the morphological kidney changes caused by doxorubicin exposure compared with the group that received doxorubicin alone. The putative mechanism is most likely related to a reduction in the oxidative stress caused by doxorubicin.

scholarly journals Spironolactone Protects against Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetic Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Wenjuan Liu ◽  
Wei Gong ◽  
Min He ◽  
Yemei Liu ◽  
Yeping Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Diabetic Cardiomyopathy ◽  
Diabetic Rats ◽  
Pathological Examination ◽  
In Vivo Model ◽  
Transmission Electron ◽  
Onset Of Diabetes

Spironolactone (SPR) has been shown to protect diabetic cardiomyopathy (DCM), but the specific mechanisms are not fully understood. Here, we determined the cardioprotective role of SPR in diabetic mice and further explored the potential mechanisms in bothin vivoandin vitromodels. Streptozotocin- (STZ-) induced diabetic rats were used as the in vivo model. After the onset of diabetes, rats were treated with either SPR (STZ + SPR) or saline (STZ + NS) for 12 weeks; nondiabetic rats were used as controls (NDCs). In vitro, H9C2 cells were exposed to aldosterone, with or without SPR. Cardiac structure was investigated with transmission electron microscopy and pathological examination; immunohistochemistry was performed to detect nitrotyrosine, collagen-1, TGF-β1, TNF-α, and F4/80 expression; and gene expression of markers for oxidative stress, inflammation, fibrosis, and energy metabolism was detected. Our results suggested that SPR attenuated mitochondrial morphological abnormalities and sarcoplasmic reticulum enlargement in diabetic rats. Compared to the STZ + NS group, cardiac oxidative stress, fibrosis, inflammation, and mitochondrial dysfunction were improved by SPR treatment. Our study showed that SPR had cardioprotective effects in diabetic rats by ameliorating mitochondrial dysfunction and reducing fibrosis, oxidative stress, and inflammation. This study, for the first time, indicates that SPR might be a potential treatment for DCM.

Sign in / Sign up

Export Citation Format

Share Document