scholarly journals Antioxidant Traits and Protective Impact of Vorinostat against Cisplatin Induced Hepatoxicity in Rats

2020 ◽  
pp. 58-73
Author(s):  
Hala Salah Abdel Kawy Eweis ◽  
Omnyah Mohammad Omar Bashraf ◽  
Ahmed Shaker Ali ◽  
Soad Shaker Ali
Keyword(s):  
Low Dose ◽  
Caspase 3 ◽  
Liver Toxicity ◽  
Control Group ◽  
Histopathological Analysis ◽  
Protective Effects ◽  
Tnf Α ◽  
Male Wistar Rats ◽  
Group Ii ◽  
Inflammatory Effect

Background and Aim: Cisplatin "cis diamminedichloroplatinum [II] (CDDP) is the most widely used drug in cancer chemotherapy and hepatotoxicity is one of its major side effects. Vorinostat (VST) has been recognized to have an antioxidant and anti-inflammatory effect in low doses. The present study aimed to explore the potential protective effects of low dose VST against CDDP induced-liver toxicity in male Wistar rats. Methods: The rats were randomly divided into 4 groups (10 rats each); I-control group, II-CDDP group (7.5 mg/kg I.P. single dose 5 days before the end of the experiment) III-, VST group (15 mg/kg/day by gastric gavage for 28 days) and IV-CDDP + VST group (as in group II & III). Blood and livers samples were collected at the day 28th for biochemical and histopathological examinations. Results: Administration of CDDP significantly decrease hepatic GSH levels and increase serum alanine transaminase, aspartate transaminase and hepatic MDA, p53, TNF-α, and NF-κB levels compared to control. Pretreatment with VST significantly attenuated all unfavorable changes in these parameters. Histopathological analysis showed that VST significantly decreased liver inflammatory and degenerative changes induced by CDDP. VST also significantly increased Bcl-2 and decreased Caspas-3 immunoexpression in hepatic tissues. Conclusion: VST alleviates CDDP induced hepatic toxicity in rats by modulating MDA, p53, TNF-α, and NF-κB. It also significantly increased Bcl-2 and decreased Caspase-3.

THE POTENTIAL MODULATORY EFFECT OF RUTIN ON TITANIUM DIOXIDE NANOPARTICLES-INDUCED RENAL INJURY IN MALE MICE

2020 ◽  
pp. 17-21
Author(s):  
HEBA A. M. MOUSA
Keyword(s):  
Renal Injury ◽  
Caspase 3 ◽  
Titanium Dioxide Nanoparticles ◽  
B Cell Lymphoma ◽  
Control Group ◽  
Protective Effects ◽  
Group Iii ◽  
Group I ◽  
Tnf Α ◽  
Factor Α

Objective: This study aimed to investigate the possible protective effect of rutin in management of TiO2NPs-induced renal injury in mice. Methods: Forty male Swiss albino mice were randomly divided into four groups (n=10). Group (I) served as a control group, group (II) received 100 mg/kg body weight (b. wt) of rutin (orally), group (III) received 70 mg/kg b. wt of TiO2NPs,injected intraperitoneally (i. p.), Group (IV) received 70 mg/kg b. wt of TiO2NPs plus 100 mg/kg b. wt of rutin; for 14 successive days. The renal toxicity was determined through evaluating the renal function biomarkers (serum creatinine, urea, and uric acid) and the levels of malondialdehyde (MDA), reduced glutathion (GSH), nuclear factor kappa B (NF-kB), tumor necrosis factor-α (TNF)-α, B-cell lymphoma (BCL)-2 and caspase-3 in renal tissues. Results: Administration of TiO2NPs plus rutin prevented the deleterious effect of TiO2NPs on mice kidneys through improving the renal functions, and alleviating the increase in MDA, NF-kB, TNF-α, and caspase-3 levels, as well as the decrease in GSH andBCL-2 levels, in renal tissues. Conclusion: Taken together, these findings suggested that rutin plays a role in alleviating TiO2NPs-induced oxidative stress, inflammation, and apoptosis, and exerts renal protective effects.

scholarly journals Protective Effects of Taurine Against Inflammation and Apoptosis in Cadmium-Induced Hepatotoxicity

2021 ◽  
Author(s):  
Jiaming Zheng ◽  
Guobin Qiu ◽  
Yewen Zhou ◽  
Kezhe Ma ◽  
Sheng Cui
Keyword(s):  
Caspase 3 ◽  
Liver Toxicity ◽  
Animal Health ◽  
Inflammatory Factor ◽  
Protective Effects ◽  
Nuclear Condensation ◽  
Vacuolar Degeneration ◽  
Protective Function ◽  
Tnf Α ◽  
Metal Contaminant

Abstract Cadmium (Cd), a heavy metal contaminant,which seriously threatens human and animal health. Taurine (Tau) has been used to against hepatotoxicity caused by different environmental toxins. However, it has not been elucidated whether Tau exerts its protective function against Cd-induced hepatotoxicity. The aim of this study was thus to evaluate the ameliorative function of Tau on Cd-induced liver toxicity in mice. The histopathologic and ultrastructure changes, as well as alterations in indexes related to liver function, antioxidant biomarkers, inflammatory and apoptosis were evaluated. The results showed that Tau alleviated the vacuolar degeneration, nuclear condensation, mitochondria swelling and cristae lysis of hepatocytes induced by Cd. In addition, Tau treatment significantly restored the ALT, AST levels in serum, and inflammatory factor TNF-α and IL-1β in liver tissue. Furthermore, Tau treatment decreased the Bax/Bcl-2 ratio and cleaved caspase-3 protein expression levels. Taken together, these observations demonstrate that Tau has important hepatic protective function against the inflammation and apoptosis induced by Cd.

scholarly journals Newly Developed Recombinant Antithrombin Protects the Endothelial Glycocalyx in an Endotoxin-Induced Rat Model of Sepsis

2020 ◽  
Vol 22 (1) ◽  
pp. 176
Author(s):  
Toshiaki Iba ◽  
Jerrold H. Levy ◽  
Koichiro Aihara ◽  
Katsuhiko Kadota ◽  
Hiroshi Tanaka ◽  
...  
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Leukocyte Adhesion ◽  
Endothelial Glycocalyx ◽  
High Dose Group ◽  
Control Group ◽  
High Dose ◽  
Protective Effects ◽  
Circulating Levels

(1) Background: The endothelial glycocalyx is a primary target during the early phase of sepsis. We previously reported a newly developed recombinant non-fucosylated antithrombin has protective effects in vitro. We further evaluated the effects of this recombinant antithrombin on the glycocalyx damage in an animal model of sepsis. (2) Methods: Following endotoxin injection, in Wistar rats, circulating levels of hyaluronan, syndecan-1 and other biomarkers were evaluated in low-dose or high-dose recombinant antithrombin-treated animals and a control group (n = 7 per group). Leukocyte adhesion and blood flow were evaluated with intravital microscopy. The glycocalyx was also examined using side-stream dark-field imaging. (3) Results: The activation of coagulation was inhibited by recombinant antithrombin, leukocyte adhesion was significantly decreased, and flow was better maintained in the high-dose group (both p < 0.05). Circulating levels of syndecan-1 (p < 0.01, high-dose group) and hyaluronan (p < 0.05, low-dose group; p < 0.01, high-dose group) were significantly reduced by recombinant antithrombin treatment. Increases in lactate and decreases in albumin levels were significantly attenuated in the high-dose group (p < 0.05, respectively). The glycocalyx thickness was reduced over time in control animals, but the derangement was attenuated and microvascular perfusion was better maintained in the high-dose group recombinant antithrombin group (p < 0.05). (4) Conclusions: Recombinant antithrombin maintained vascular integrity and the microcirculation by preserving the glycocalyx in this sepsis model, effects that were more prominent with high-dose therapy.

scholarly journals Hepatoprotective effect of galangin on carbon tetrachloride-induced hepatotoxicity via the LKB1/AMPK pathway

2021 ◽  
Vol 19 ◽  
pp. 205873922110008
Author(s):  
Meng Chen ◽  
Xinyan Song ◽  
Jifang Jiang ◽  
Lei Xing ◽  
Pengfei Wang
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Toxicity ◽  
Corn Oil ◽  
Histopathological Examination ◽  
Hepatoprotective Effect ◽  
Control Group ◽  
Group Model ◽  
Protective Effects ◽  
Model Group ◽  
Expression Levels

To investigate the protective effects of galangin on liver toxicity induced by carbon tetrachloride (CCl4) in mice. Mouse hepatotoxicity model was established by intraperitoneal injection (i.p.) of 10 ml/kg body weight CCl4 that diluted with corn oil to a proportion of 1:500 on Kunming mice. The mice were randomly divided into five groups named control group, model group, and 1, 5, and 10 mg/kg galangin group. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed by ELISA. Liver histopathological examination was observed via optical microscopy. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), and glutathion (GSSG) were analyzed to assess oxidative stress. Finally, western blot assay was carried out to analyse the expression levels of total AMP-activated protein kinase (AMPK), phospho-AMPK (p-AMPK), total liver kinase B1 (LKB1), and phospho-LKB1 (p-LKB1). Compared with the control group, in the model group, the levels of AST, ALT, MDA, and GSSG increased significantly ( p < 0.01); the activity of SOD and GSH decreased significantly ( p < 0.01); and the histopathological examination revealed liver necrosis. However, treatment with galangin (5 and 10 mg/kg) significantly reversed these CCl4-induced liver damage indicators. Furthermore, treatment with galangin (10 mg/kg) significantly increased the p-AMPK and p-LKB1 expression levels ( p < 0.01). This study supports the hepatoprotective effect of galangin against hepatotoxicity, perhaps occurring mainly through the LKB1/AMPK-mediated pathway.

Effect of Curculigo orchioides on Reflux Esophagitis by Suppressing Proinflammatory Cytokines

2012 ◽  
Vol 40 (06) ◽  
pp. 1241-1255 ◽  
Author(s):  
Sae-Kang Ku ◽  
Jae-Soo Kim ◽  
Young-Bae Seo ◽  
Yong-Ung Kim ◽  
Seung-Lark Hwang ◽  
...  
Keyword(s):  
Reflux Esophagitis ◽  
Group Treatment ◽  
Control Group ◽  
Esophageal Mucosa ◽  
Dependent Manner ◽  
Protective Effects ◽  
Model Group ◽  
Curculigo Orchioides ◽  
Intact Group ◽  
Tnf Α

This study was performed to investigate effects of Curculigo orchioides rhizome (curculiginis rhizome) on acute reflux esophigitis (RE) in rats that are induced by pylorus and forestomach ligation operation. Proinflammatory cytokine, as well as tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were all assayed and the expression of TNF-α and COX2 analyzed by RT-PCR. The esophagic tissue damage of reflux esophagitis rat was increased compared to that of normal intact group. However, the esophagic damage percentage from the extract of curculiginis rhizoma (ECR) 600 mg/kg and ECR 300 mg/kg were significantly lower than that of the RE control group. Administration of α-tocopherol (30 mg/kg) and ECR (600 mg/kg, 300 mg/kg, and 150 mg/kg) had a significant effect on the gastric acid pH in rats with induced reflux esophagitis (p < 0.05). The treatment with ECR significantly reduced the production of cytokines TNF-α, IL-1β and IL-6 levels compared to the model group (p < 0.05). The expression of TNF-α and COX2 in the intact esophageal mucosa was low while those of the RE control group were significantly higher due to an inflammatory reaction in the esophagus. Compare to the model group, treatment with α-tocopherol or ECR significantly inhibited the expression levels of COX2 and TNF-α in a dose-dependent manner. These results suggest that anti-inflammatory and protective effects of ECR could attenuate the severity of reflux esophagitis and prevent esophageal mucosal damage.

scholarly journals Effects of low-dose aspirin on the osseointegration process in rats

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ana Carolina Lupepsa ◽  
Paula Vargas-Sanchez ◽  
Marcella Goetz Moro ◽  
Leomar Emanuel Almeida Mecca ◽  
Marcela Claudino ◽  
...  
Keyword(s):  
Low Dose ◽  
Inhibitory Effect ◽  
Control Group ◽  
Implant Placement ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Male Wistar Rats ◽  
Bone To Implant Contact ◽  
Bone Deposition

Abstract Background Several drugs are capable of promoting changes in bone metabolism. The aim of this study was to evaluate the effect of long-term low-dose aspirin (LDA) therapy on implant osseointegration. Methods Male Wistar rats were divided into 4 groups (n = 8/group) according to oral gavage solution received prior (42 days) to the implant surgery on the tibia. The control group was treated with saline solution for 7 (CG-7) and 28 (CG-28) days. The use of low-dose aspirin was performed in AG groups (6.75 mg/kg of aspirin) for 7 (AG-7) and 28 (AG-28) days. After experimental periods, histomorphometric evaluation of bone-to-implant contact (BIC) and the bone area between threads (BABT) was performed. Results Reduced BIC values were detected in AG-7 (62.8% ± 17.1) group compared to AG-28 (91.9% ± 5.4), CG-7 (82.7% ± 15.2), and CG-28 (89.9% ± 9.7). BABT evaluation revealed lower values in AG-7 (70.9% ± 15.2) compared to AG-28 (95.4% ± 3.7) and CG-28 (87.1% ± 10.2) groups. Conclusions The treatment with low doses of aspirin promoted a discrete inhibitory effect in the early stages (7 days) of repair after implant placement, specifically in the bone deposition. However, these effects were not detected in the late stages (28 days), considering BIC and BABT parameters.

scholarly journals Histopathological analysis of gangliosides use in peripheral nerve regeneration after axonotmesis in rats

2008 ◽  
Vol 23 (4) ◽  
pp. 364-371 ◽  
Author(s):  
Camila Maria Beder Ribeiro ◽  
Belmiro Cavalcanti do Egito Vasconcelos ◽  
Joaquim Celestino da Silva Neto ◽  
Valdemiro Amaro da Silva Júnior ◽  
Nancy Gurgel Figueiredo
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Schwann Cells ◽  
Peripheral Nerve Regeneration ◽  
Cell Activity ◽  
Control Group ◽  
Histopathological Analysis ◽  
Male Wistar Rats ◽  
The Right

PURPOSE: To analyze the action of gangliosides in peripheral nerve regeneration in the sciatic nerve of the rat. METHODS: The sample was composed of 96 male Wistar rats. The animals were anaesthetized and, after identification of the anaesthesic plane, an incision was made in the posterior region of the thigh, followed by skin and muscle divulsion. The right sciatic nerve was isolated and compressed for 2 minutes. Continuous suture of the skin was performed. The animals were randomly divided into two groups: the experimental group (EG), which received subcutaneous injection of gangliosides, and the control group (CG), which received saline solution (0.9%) to mimic the effects of drug administration. RESULTS: No differences were observed between the experimental and control groups evaluated on the eighth day of observation. At 15 and 30 days the EG showed an decrease in Schwann cell activity and an apparent improvement in fibre organization; at 60 days, there was a slight presence of Schwann cells in the endoneural space and the fibres were organized, indicating nerve regeneration. At 15 and 30 days, the level of cell reaction in the CG had diminished, but there were many cells with cytoplasm in activity and in mitosis; at 60 days, hyperplastic Schwann cells and mitotic activity were again observed, as well as nerve regeneration, but to a lesser extent than in the EG. CONCLUSION: The administration of exogenous gangliosides seems to improve nerve regeneration.

scholarly journals Perfluorooctanoic Acid Exposure in Early Pregnancy Induces Oxidative Stress in The Uterus and Liver in Mice

2021 ◽  
Author(s):  
Yan Zhang ◽  
Linchao Zhang ◽  
JiaLu Bao ◽  
LianTao Liu ◽  
Xiaodan Wang
Keyword(s):  
Early Pregnancy ◽  
Caspase 3 ◽  
Liver Toxicity ◽  
Liver Weight ◽  
Perfluorooctanoic Acid ◽  
Control Group ◽  
Dependent Manner ◽  
Subsequent Increase ◽  
Decidual Cells ◽  
Pregnant Mice

Abstract To investigate the mechanism perfluorooctanoic acid (PFOA)’s toxicity on the uterus and liver of the mice during early pregnancy, pregnant mice were given 0, 1, 5, 10, 20, 40 mg/kg PFOA daily by gavage from gestational day (GD) 1-7, and sacrificed on GD 9. Uterus and liver weight were recorded, liver and uterine indexes were calculated, histopathological changes of the liver and uterus were examined, and levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) in liver were detected by spectrophotometric method. Expression of FAS, FASL, Bax, Bcl-2, and Caspase-3 in decidual cells were detected by immunohistochemistry and the TUNEL method was used to detect apoptotic uterine cells. Results showed that liver weight increased, and the uterus index was significantly reduced at 40 mg/kg compared with the control group. With increasing doses of PFOA, levels of SOD and GSH-PX were significantly decreased, and MDA significantly increased in liver tissue. 20 mg/kg and 40 mg/kg of PFOA caused greater harm to the uterus and congestion and resorption may occur. Expression of FAS, FASL, Bax, and Caspase-3 in decidual cells of the uterus in PFOA treatment groups significantly increased in a dose-dependent manner. The expression of Bcl-2 was down-regulated, which decreased the ratio of Bcl-2/Bax. It is therefore proposed that oxidative damage may be one of the mechanisms by which PFOA induces liver toxicity, and a subsequent increase in uterine cell apoptosis may induce embryo loss or damage.

scholarly journals Effectiveness of Vitamin C and Vitamin E Antioxidant Combination on Caspase-3 Expression in Wistar White Rat Pulmonum Contusion

2020 ◽  
Vol 3 (1) ◽  
pp. 31-44
Author(s):  
Bermansyah ◽  
Gama Satria ◽  
Ahmad Umar
Keyword(s):  
Cell Death ◽  
Vitamin E ◽  
Vitamin C ◽  
Wistar Rats ◽  
Caspase 3 ◽  
Cell Function ◽  
Pulmonary Contusion ◽  
Tnf Α ◽  
Male Wistar Rats

Introduction.Pulmonary contusions can cause a progressive inflammatory response. Activation of TNF-α cytokines and reactive oxygen species (ROS) can cause pulmonary cell death. Antioxidants can have the potential to neutralize ROS. The purpose of this study is to determine the effectiveness of antioxidant administration in maintaining pulmonary cell function in wistar rats that have been induced to experience pulmonary contusions through caspase-3 levels. Methods.This study was an in vivo experimental study conducted on thirty male wistar rats and divided into five groups (n = 6): control, pulmonary contusion + asthaxanthine 5 mg/kgBW, pulmonary contusion + vitamin C and E 50 mg/kgBW, pulmonary contusion + vitamin C and E 100 mg/kgBW, pulmonary contusion + vitamin C and E 200 mg/kgBW. The value of Caspase-3 is evaluated by the IHC. All data analyzes used SPSS 18. Results. Low doses of antioxidants have the potential to reduce pulmonary cell death in wistar rats induced by pulmonary contusions.Conclussion. Vitamin C and E effective to reduce polmonary cell death in pulmonary contusion.Keywords: antioxidants, vitamin C, vitamin E, pulmonary contusions animal model, apoptosis, caspase-3

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