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 Safety of Aqueous Extract of Calea ternifolia Used in Mexican Traditional Medicine

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Ma G. E. González-Yáñez ◽  
Catalina Rivas-Morales ◽  
María A. Oranday-Cárdenas ◽  
María J. Verde-Star ◽  
María A. Núñez-González ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Aqueous Extract ◽  
Histological Analysis ◽  
Liver Enzymes ◽  
Renal Tissue ◽  
Proximal Tubules ◽  
Hepatic Toxicity ◽  
Treatment Of Diabetes

There is a trend to use medicinal plants for primary medical care or as dietary supplements; however, the safety of many of these plants has not been studied. The objective of this work was to determine the toxic effect of the aqueous extract of Calea ternifolia (C. zacatechichi), known popularly as “dream herb” in vivo and in vitro in order to validate its safety. In vivo, the extract had moderate toxicity on A. salina. In vitro, the extract induced eryptosis of 73% at a concentration of 100 μg·mL−1 and it inhibited CYP3A by 99% at a concentration of 375 μg/mL. After administering 8.5 mg/kg of C. ternifolia to rats, we found a reduction in platelets and leukocytes and an increase in urea and the liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). Histological analysis showed spongiform changes in the proximal tubules of renal tissue and a lymphoid infiltrate in liver tissue. This plant is used in the treatment of diabetes, and it is commercialized as a dietary supplement in several countries. Our results show renal and hepatic toxicity; therefore, more profound research on the toxicity of this plant is needed.

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 Sulforaphane Attenuates Contrast-Induced Nephropathy in Rats via Nrf2/HO-1 Pathway

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Zhihong Zhao ◽  
Guixiang Liao ◽  
Qin Zhou ◽  
Daoyuan Lv ◽  
Harry Holthfer ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Model ◽  
Renal Tissue ◽  
Antioxidant Defenses ◽  
Control Group ◽  
Heme Oxygenase 1 ◽  
Contrast Induced Nephropathy ◽  
Hk2 Cells

Background. Oxidative stress plays an important role in the pathogenesis of contrast-induced nephropathy (CIN). The aim of this study was to investigate the antioxidant effects of sulforaphane (SFN) in a rat model of CIN and a cell model of oxidative stress in HK2 cells.Methods. Rats were randomized into four groups (n=6per group): control group, Ioversol group (Ioversol-induced CIN), Ioversol + SFN group (CIN rats pretreated with SFN), and SFN group (rats treated with SFN). Renal function tests, malondialdehyde (MDA), and reactive oxygen species (ROS) were measured. Western blot, real-time polymerase chain reaction analysis, and immunohistochemical analysis were performed for nuclear factor erythroid-derived 2-like 2 (Nrf2) and heme oxygenase-1 (HO-1) detection.Results. Serum blood urea nitrogen (BUN), creatinine, and renal tissue MDA were increased after contrast exposure. Serum BUN, creatinine, and renal tissue MDA were decreased in the Ioversol + SFN group as compared with those in the Ioversol group. SFN increased the expression of Nrf2 and HO-1 in CIN rats and in Ioversol-induced injury HK2 cells. SFN increased cell viability and attenuated ROS level in vitro.Conclusions. SFN attenuates experimental CIN in vitro and in vivo. This effect is suggested to activate the Nrf2 antioxidant defenses pathway.

scholarly journals Persea americana Leaf Ethyl Acetate Extract Phytochemical, In-vitro Antioxidant and In-vivo Potentials to Mitigate Oxidative Stress in Alloxan-induced Hyperglycaemic Rats

2019 ◽  
pp. 1-11
Author(s):  
J. A. Mashi ◽  
A. M. Sa’id ◽  
R. I. Idris ◽  
I. Aminu ◽  
A. A. Muhammad ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Ethyl Acetate ◽  
Ethyl Acetate Extract ◽  
Diabetic Rats ◽  
Persea Americana ◽  
Albino Rats ◽  
Standard Drug

The purpose of this study was to investigate the in-vivo and in-vitro potentials of ethyl acetate extract of P. americana leaf in alloxan-induced diabetic rats. Quantitative phytochemicals analyzed includes; flavonoids, saponins, tannins, alkaloids and phenolics. Measurement of antioxidant activity using 1,1-Diphenyl-2-picrylhydrazyl, total antioxidant capacity, hydroxyl radical, hydrogen peroxide, superoxide radical and ferric reducing activity of the extract was carried out. Hyperglycemia was induced by intraperitoneal injection of alloxan monohydrate to albino rats. In-vivo anti-oxidant potentials of the extract were evaluated by measuring liver homogenate activity of superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase and malondyaldehyde in alloxan-induced diabetic rats administered with the extract.  A total of 30 Albino rats were used for this experiment and they were divided into six groups of 5 rats each. Group A; normal control, Group B; diabetic control, Groups C-E; experimental groups administered with different doses (100, 200 and 400 mg/kg body weight respectively); of the extract and Group F; glucophage (84 mg/kg body weight, standard drug) for 4 weeks. This study was conducted in the Department of Biochemistry, Bayero University, Kano, in August, 2018. Data was analyzed using one-way ANOVA with P=.05 value considered as significant. Results of the quantitative phytochemical investigation shows that the extract is rich in phenolics (184.1±0.6), flavonoids (115.8±2.1), alkaloids (41.5±1.8), with least concentration of tannis (21.2±0.8) and saponins (15.2±2.3). The extract exhibited high radical scavenging activity against synthetic free radicals (DPPH), reactive oxygen species (peroxide, superoxide and hydroxyl acid) and high ability to reduce Fe3+ to Fe2+ (FRAP). The activities of antioxidant enzymes of the treated rats were increased significantly (P=.05) while the level malondyaldehyde was significantly decreased (P=.05) in the treated groups. Ethyl acetate leaf extract of Persea americana contains phytochemical substances which improved antioxidant status and can be use as herbal therapy for the management of oxidative stress induced by diabetes mellitus and associated complications.

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.

scholarly journals Inhibition of PRMT5 Attenuates Oxidative Stress-Induced Pyroptosis via Activation of the Nrf2/HO-1 Signal Pathway in a Mouse Model of Renal Ischemia-Reperfusion Injury

2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Changhui Diao ◽  
Zhiyuan Chen ◽  
Tao Qiu ◽  
Hao Liu ◽  
Yuanyuan Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Mouse Model ◽  
Ischemia Reperfusion ◽  
Renal Tissue ◽  
Arginine Methylation ◽  
Tubular Epithelium ◽  
Related Proteins

Background. Extensive evidence has demonstrated that oxidative stress, pyroptosis, and proinflammatory programmed cell death are related to renal ischemia/reperfusion (I/R) injury. However, the underlying mechanism remains to be illustrated. Protein arginine methylation transferase 5 (PRMT5), which mediates arginine methylation involved in the regulation of epigenetics, exhibits a variety of biological functions and essential roles in diseases. The present study investigated the role of PRMT5 in oxidative stress and pyroptosis induced by I/R injury in a mouse model and in a hypoxia/reoxygenation (H/R) model of HK-2 cells. Methods. C57 mice were used as an animal model. All mice underwent right nephrectomy, and the left renal pedicles were either clamped or not. Renal I/R injury was induced by ligating the left renal pedicle for 30 min followed by reperfusion for 24 h. HK-2 cells were exposed to normal conditions or stimulation through H/R. EPZ015666(EPZ)—a selective potent chemical inhibitor—and small interfering RNA (siRNA) were administered to suppress the function and expression of PRMT5. The levels of urea nitrogen and creatinine in the serum and renal tissue injury were assessed. Immunohistochemistry, western blotting, and reverse transcription-polymerase chain reaction were used to evaluate pyroptosis-related proteins including nod-like receptor protein-3, ASC, caspase-1, caspase-11, GSDMD-N, and interleukin-1β. Cell apoptosis and cell viability were detected through flow cytometry, and the levels of reactive oxygen species (ROS) and hydrogen peroxide (H2O2) were measured. Ki-67 was used to assess the proliferation of renal tubular epithelium. In addition, the activity of malondialdehyde and superoxide dismutase was determined. Results. I/R or H/R induced an increase in the expression of PRMT5. Inhibition of PRMT5 by EPZ alleviated oxidative stress and I/R- or H/R-induced pyroptosis. In renal tissue, the application of EPZ promoted the proliferation of tubular epithelium. In addition, H/R-induced pyroptosis in HK-2 cells was dependent on oxidative stress in vitro. Administration of either EPZ or siRNA led to decreased expression of pyroptosis-related proteins. Inhibition of PRMT5 also attenuated the I/R- or H/R-induced oxidative stress in vivo and in HK-2 cells, respectively. It also resulted in a distinct decrease in the levels of malondialdehyde and H2O2, and an apparent increase in superoxide dismutase activity in mouse renal tissue. Moreover, it led to a significant decrease in the levels of ROS and H2O2 in HK-2 cells. When activated, NF-E2-related factor/heme oxygenase-1 (Nrf2/HO-1)—a key regulator of various cytoprotective proteins that withstand oxidative damage—can decrease the generation of ROS. Nrf2/HO-1 was downregulated during I/R in tissues and H/R in HK-2 cells, and this effect was reversed by the PRMT5 inhibitor. Furthermore, the expressions of Nrf2 and HO-1 proteins were markedly upregulated by EPZ or siRNA against PRMT5. Conclusion. PRMT5 is involved in ischemia- and hypoxia-induced oxidative stress and pyroptosis in vitro and in vivo. Inhibition of PRMT5 may ameliorate renal I/R injury by suppressing oxidative stress and pyroptosis via the activation of the Nrf2/HO-1 pathway, as well as promoting the proliferation of tubular epithelium. Therefore, PRMT5 may be a promising therapeutic target.

scholarly journals N-acetylcysteine+nimesulide: An association strategy aiming to prevent nimesulide-induced hepatotoxicity

2021 ◽  
Vol 19 (2) ◽  
pp. 91-99
Author(s):  
Amanda G. Elias ◽  
Julia S. da Silva ◽  
Rafaela L. Klein ◽  
Francieli U. I. Amaral ◽  
Marcelo D. Arbo ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Cell Model ◽  
Body Weight Gain ◽  
The Body ◽  
Relative Mass ◽  
Male Wistar Rats ◽  
Control Body

Introduction: Nimesulide is a potent anti-inflammatorywith rapid and long-lasting effects, but also with a high riskof hepatotoxicity. Objective: This work aimed to preventnimesulide-induced hepatotoxicity through the associationof nimesulide with a hepatoprotective agent. Materials andMethods: First, we tested three hepatoprotective agents:N-acetylcysteine, L-carnitine, and Gingko biloba extract inan in vitro hepatic cell model. Both N-acetylcysteine and G.biloba showed promisor results. We selected N-acetylcysteineto continue the studies in an animal model. In vivo study wasperformed using male Wistar rats divided in 4 groups: control,nimesulide (100mg/kg/day), nimesulide (100mg/kg/day) +N-acetylcysteine (100mg/kg/day) and N-acetylcysteine alone(100mg/kg/day). Treatments were given by gavage, daily, for15 days. Results: Animals receiving nimesulide alone showedlower body weight gain compared to control. Body weightgain in the nimesulide + N-acetylcysteine group was higherthan nimesulide alone, evidencing lower toxicity. However,the body weight gain of the nimesulide + N-acetylcysteinegroup was still lower than the control animals. Animals treatedwith nimesulide alone presented an increased relative mass ofheart, liver, and spleen and significant hepatic damage seen inmicroscopy when compared to other groups. N-acetylcysteineco-administered with nimesulide prevented the increasedheart mass, but the same was not true with liver and spleen.Conclusions: This work evidence partial protection elicitedby the association of N-acetylcysteine and nimesulide againstnimesulide-induced hepatotoxicity.

Effects of amiodarone on 5′-deiodination of thyroxine to tri-iodothyronine in rat myocardium

1989 ◽  
Vol 121 (3) ◽  
pp. 431-434 ◽  
Author(s):  
J. A. Ceppi ◽  
A. A. Zaninovich
Keyword(s):  
Body Weight ◽  
Phosphate Buffer ◽  
Wistar Rats ◽  
Type Ii ◽  
Rat Myocardium ◽  
Iopanoic Acid ◽  
Male Wistar Rats ◽  
Expected Increase

ABSTRACT The present work studied the effects of amiodarone (AMD) and iopanoic acid (IA) on the conversion of thyroxine (T4) to tri-iodothyronine (T3) by rat myocardium. In vivo: male Wistar rats weighing 200–250 g were injected i.p. with AMD (2·5 mg/100 g body weight per day for 12 days) or IA (5 mg/100 g body weight every 12 h for 72 h). Hearts were then removed and processed as in the in-vitro studies. In vitro: hearts were homogenized in Krebs–Ringer phosphate buffer (pH 7·4) and AMD (0·1 mmol/l) or IA (10 mmol/l) plus dithiothreitol (8 mmol/l) and 0·01 μCi [125I]T4 or [125I]T3 were added. After incubation for 2 h at 37 °C, radioactive compounds were identified by paper chromatography. Both AMD and IA given in vivo blocked T4 to T3 conversion significantly (P<0·005). When added in vitro, AMD failed to inhibit T4 deiodination to T3 whereas IA induced a significant (P<0·005) decrease in T3 generation. Deiodination of [125I]T3 by heart homogenates was not altered by AMD or IA. While the expected increase in circulating T4 (P< 0·001) and decrease in T3 (P< 0·001) did occur after AMD or IA treatment, plasma TSH in AMD-treated rats was decreased (P<0·001), while in IA-treated animals it was increased (P< 0·001), thus indicating that AMD did not inhibit pituitary type-II 5′-monodeiodinase. In summary, these data suggest that the hypometabolism induced by AMD in rat myocardium through a decrease in the supply of T3 is not responsible for the anti-arrhythmic activity of this drug since IA, which is not an anti-arrhythmic compound, elicited the same effect on cardiac T3. It follows that inhibition of 5′-deiodinase and the anti-arrhythmic activity of AMD are independent properties. Journal of Endocrinology (1989) 121, 431–434

Lipophilic Extract and Tanshinone IIA Derived from Salvia miltiorrhiza Attenuate Uric Acid Nephropathy through Suppressing Oxidative Stress-Activated MAPK Pathways

2020 ◽  
Vol 48 (06) ◽  
pp. 1455-1473
Author(s):  
Xiao-Wei Zhang ◽  
Mei Zhou ◽  
Lin An ◽  
Ping Zhang ◽  
Ping Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Uric Acid ◽  
Salvia Miltiorrhiza ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Renal Tissue ◽  
Tanshinone Iia ◽  
Mapk Pathways ◽  
Uric Acid Nephropathy

Uric acid nephropathy (UAN) is caused by excessive uric acid, which results in the damage of renal tissue via urate crystals deposition in the kidneys. The roots and rhizomes of Salvia miltiorrhiza Bunge (S. miltiorrhiza) have been clinically used in many prescriptions to treat uric acid-induced renal damage. This study investigates the uricosuric and nephroprotective effects of the ethyl acetate extract of S. miltiorrhiza (EASM) and tanshinone IIA (a major component of S. miltiorrhiza, Tan-IIA) on UAN and explores the underlying molecular mechanism. Both EASM and Tan-IIA significantly decreased serum uric acid (SUA), serum creatinine (SCR), urine uric acid (UUA), and increased urine creatinine (UCR), and blood urea nitrogen (BUN) levels in experimental UAN mice. In adenine and potassium oxonate-induced mice, EASM and Tan-IIA treatment alleviated renal dysfunction and downregulated the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Moreover, EASM treatment significantly prevented excessive reactive oxygen species (ROS) production in uric acid-induced HK-2 cells and suppressed the expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4). EASM also suppressed ROS-activated mitogen-activated protein kinases (MAPKs) in vivo and in vitro. These results suggest that both EASM and Tan-IIA demonstrated inhibitory effects on UAN through relieving NOX4-mediated oxidative stress and suppressing MAPK pathways activation.

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