Sodium Citrate Inhibits Endoplasmic Reticulum Stress in Rats with Adenine-Induced Chronic Renal Failure

2015 ◽  
Vol 42 (1) ◽  
pp. 14-21 ◽  
Author(s):  
Yan Ou ◽  
Wenqian Hou ◽  
Shuiqin Li ◽  
Xiaojing Zhu ◽  
Yan Lin ◽  
...  
Keyword(s):  
Renal Failure ◽  
Endoplasmic Reticulum ◽  
Chronic Renal Failure ◽  
Endoplasmic Reticulum Stress ◽  
Western Blot ◽  
Low Dose ◽  
Sodium Citrate ◽  
Control Group ◽  
High Dose ◽  
Model Group

Background/Aims: Endoplasmic reticulum stress (ERS) is an important self-protective cellular response to harmful stimuli that contribute to various diseases, including chronic renal failure (CRF). Sodium citrate plays an important role in antioxidant and cellular immunity, but whether it improves ERS in CRF is unclear. Methods: The rats were randomly divided into five groups: the control group, the sodium citrate control group, the model group, model rats with low dose sodium citrate (216 mg/kg), and model rats with a high dose of sodium citrate (746 mg/kg). The rats were euthanized at 6, 8, 12, and 16 weeks with their blood and renal tissue in detection. Results: The increased concentrations of blood urea nitrogen and serum creatinine in the model group were significantly decreased by sodium citrate treatment. Hematoxylin-eosin and Masson staining showed that sodium citrate treatment apparently improved renal pathological changes in CRF rats. Western blot analysis showed that sodium citrate treatment decreased the protein levels of transforming growth factor-beta 1 and collagen type IV, which were increased in model rats. Moreover, immunohistochemical staining demonstrated that sodium citrate could effectively reduce the protein expression of glucose-regulated protein 78 kDa and CCAAT/enhancer-binding protein homologous protein in the model rats, which was consistent with western blot results. Additionally, the high dose of sodium citrate had a stronger protective effect in CRF rats than the low dose of sodium citrate. Conclusions: Sodium citrate has a protective effect on CRF through its effects on ERS.

scholarly journals Crocin Improves Cognitive Behavior in Rats with Alzheimer's Disease by Regulating Endoplasmic Reticulum Stress and Apoptosis

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Ling Lin ◽  
Guoliang Liu ◽  
Lina Yang
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Western Blot ◽  
Learning And Memory ◽  
Neuronal Apoptosis ◽  
Apoptotic Cell ◽  
Cell Number ◽  
Control Group ◽  
Model Group ◽  
Memory Acquisition

Aim. To investigate the effect of crocin on the learning and memory acquisition of AD rats and its underlying mechanisms. Methods. A total of 48 healthy male SD rats were randomly divided into control group, AD model group, resveratrol group, and crocin group, with 12 rats per group. AD model was established by injecting Aβ25–35 to the lateral ventricle of rats, and thereafter the rats were administrated with resveratrol (40 mg/kg), crocin (40 mg/kg), or PBS daily for 14 days. Y-maze test and sucrose preference test were used to detect the learning and memory acquisition of rats. Neuronal apoptosis was detected by TUNEL staining and Western blot for apoptosis-related proteins Bax, Bcl-2, and Caspase-3. Immunofluorescence staining and Western blot tests were used to detect the expression of glucose regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) in hippocampal CA1 region (Hippo) and prefrontal cortical neurons (PFC). Results. The learning and memory abilities of AD rats were significantly decreased, which was significantly rescued by resveratrol and crocin. The apoptotic cell number of Hippo and PFC neurons in AD model group was significantly higher than that in control group (P<0.01), while resveratrol and crocin significantly decreased the apoptotic cell number in AD group (P<0.01). Compared with the control group, the expression of Bcl2 in PFC and hippo of AD model group was significantly decreased (P<0.01), while those of Bax, Caspase3, GRP78, and CHOP were significantly increased (P<0.01). Resveratrol and crocin could significantly reverse the expression of these proteins in AD rats (P<0.05). Conclusion. Crocin can improve the learning and memory ability of AD rats possibly by reducing endoplasmic reticulum stress and neuronal apoptosis.

scholarly journals Gengnianchun Recipe Protects Ovarian Reserve of Rats Treated by 4-Vinylcyclohexene Diepoxide via the AKT Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Fangui Zhao ◽  
Wenjun Wang
Keyword(s):  
Ovarian Reserve ◽  
Low Dose ◽  
Control Group ◽  
High Dose ◽  
Model Group ◽  
Menopausal Syndrome ◽  
Primordial Follicles ◽  
Akt Phosphorylation ◽  
Vinylcyclohexene Diepoxide ◽  
Sd Rats

Diminished ovarian reserve (DOR) refers to a decrease in the number and quality of oocytes. Western treatment of DOR does not improve the ovarian reserve fundamentally, and the effect is limited. Gengnianchun recipe (GNC) is a traditional Chinese medicine formula originally applied to treat menopausal syndrome but is also found to be effective in treating clinical DOR patients. Here we aim to examine the effect of GNC in a DOR rat model induced by 4-vinylcyclohexene diepoxide (VCD), a chemical that selectively destroys ovarian small preantral follicles, and further investigate the possible mechanisms. Female SD rats were randomly divided into four groups: control group (C), model group (M), high-dose GNC group (H), and low-dose GNC group (L). Rats in M, H, and L were administered with VCD and normal saline, high-dose GNC, and low-dose GNC separately. Rat ovaries were harvested either to conduct HE staining for follicle count, immunohistochemistry, or western blot. We found that high dose of GNC significantly increased the ovarian index and sustained the number of primordial follicles and primary follicles in VCD treated rats. Moreover, high dose of GNC significantly increased the ovarian protein expression of mouse vasa homologue (MVH), anti-Müllerian hormone (AMH), follicle-stimulating hormone receptor (FSHR), and estrogen receptor β (ERβ) compared with that in the model group. Besides, high-dose GNC significantly increased ovarian AKT phosphorylation and the expression of downstream forkhead box O3 (FOXO3a). Proapoptosis proteins of Bax, cleaved caspase-3, and poly ADP-ribose polymerase (PARP) were significantly decreased after high-dose GNC treatment compared with those in the model group. Taken together, these findings suggest that high-dose GNC could protect ovarian reserve against VCD-induced toxicity via the activation of the AKT signaling pathway and reduced cell apoptosis in SD Rats. This effect could either be induced by the increased FSHR signaling or by the nontranscriptional activation of ERβ, which requires further investigation.

scholarly journals Effect of Berberine from Coptis chinensis on Apoptosis of Intestinal Epithelial Cells in a Mouse Model of Ulcerative Colitis: Role of Endoplasmic Reticulum Stress

2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Shen Yan ◽  
Liu Yingchao ◽  
Wang Zhangliu ◽  
Ruan Xianli ◽  
Li Si ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Endoplasmic Reticulum ◽  
Epithelial Cells ◽  
Endoplasmic Reticulum Stress ◽  
Caspase 3 ◽  
Intestinal Epithelial Cells ◽  
High Dose ◽  
Intestinal Epithelial ◽  
Model Group ◽  
Caspase 12

The purpose of this study was to verify the effect of berberine (BBR) on endoplasmic reticulum stress (ERS) and apoptosis of intestinal epithelial cells (IECs) in mice with ulcerative colitis (UC). BALB/c mice were randomly divided into five groups as follows: blank control, model, and low-, medium-, and high-dose BBR. A dextran sodium sulfate- (DSS-) induced model of UC was prepared, and the low-, medium-, and high-dose BBR groups were simultaneously gavaged with a BBR suspension for 7 d. Disease activity index (DAI) was assessed, and tissue damage index (TDI) was assessed from colon samples after the last administration. TUNEL assays were used to detect apoptosis of IECs. Immunohistochemistry and/or real-time PCR were applied to determine the expression of GRP78, caspase-12, and caspase-3. In all BBR treatment groups, clinical symptoms of colitis and histopathological damage were significantly reduced. The high-dose BBR group exhibited particularly pronounced decrease (p<0.01) in both DAI (0.48 ± 0.36) and TDI (1.62 ± 0.64) relative to the model group (1.50 ± 0.65 and 3.88 ± 0.04, respectively). In colon tissues of the model group, the number of apoptotic IECs was significantly increased; the expression of GRP78, caspase-12, and caspase-3 proteins was significantly increased; and the expression of the GRP78 mRNA was upregulated. In low-, medium-, and high-dose BBR groups, the number of apoptotic IECs was significantly reduced. Moreover, GRP78 and caspase-3 expression levels were significantly decreased in the medium- and high-dose BBR groups, caspase-12 expression was significantly decreased in the high-dose BBR group, and the GRP78 mRNA expression level was significantly decreased in the high-dose BBR group. BBR can effectively reduce the rate of IEC apoptosis in UC mice and alleviate the inflammatory response in the colon. The underlying mechanism seems to involve ERS modulation and inhibition of ERS-mediated activation of the caspase-12/caspase-3 apoptosis signaling pathway.

Effect of Pioglitazone on endoplasmic reticulum stress regarding in situ perfusion rat model

2021 ◽  
pp. 1-15
Author(s):  
Vivien Telek ◽  
Luca Erlitz ◽  
Ibitamuno Caleb ◽  
Tibor Nagy ◽  
Mónika Vecsernyés ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Western Blot ◽  
Rat Model ◽  
Ischemia Reperfusion ◽  
Effective Dosage ◽  
Control Group ◽  
Histopathological Changes ◽  
In Situ Perfusion

BACKGROUND: Ischemia-reperfusion injury (IRI) can cause insufficient microcirculation of the transplanted organ and results in a diminished and inferior graft survival rate. OBJECTIVE: This study aimed to investigate the effect of different doses of an anti-diabetic drug, Pioglitazone (Pio), on endoplasmic reticulum stress and histopathological changes, using an in situ perfusion rat model. METHODS: Sixty male Wistar rats were used and were divided into six groups, consisting of the control group, vehicle-treated group and four Pio-treated groups (10, 20, 30 and 40 mg/kg Pio was administered). The rats were perfused through vena cava and an outflow on the abdominal aorta occurred. Following the experiment, kidneys and livers were collected. The level of the endoplasmic reticulum stress markers (XBP1 and Caspase 12) was analyzed using Western blot and histopathological changes were evaluated. RESULTS: Histopathological findings were correlated with the Western blot results and depict a protective effect corresponding to the elevated dosage of Pioglitazone regarding in situ perfusion rat model. CONCLUSIONS: In our study, Pioglitazone can reduce the endoplasmic reticulum stress, and the most effective dosage proved to be the 40 mg/kg Pio referencing the kidney and liver samples.

scholarly journals Effects of Resveratrol on the Mechanisms of Antioxidants and Estrogen in Alzheimer’s Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Danli Kong ◽  
Yan Yan ◽  
Xiao-Yi He ◽  
Huihuang Yang ◽  
BiYu Liang ◽  
...  
Keyword(s):  
Protein Expression ◽  
Western Blot ◽  
Brain Tissue ◽  
Low Dose ◽  
Mrna Level ◽  
High Dose ◽  
Model Group ◽  
Protein Levels ◽  
Mda Content ◽  
The Brain

Objective. To observe the effects of resveratrol (Res) on the antioxidative function and estrogen level in an Alzheimer’s disease (AD) mouse model. Methods. First, we examined the effects of Res on an AD mice model. SAMP8 mice were selected as the model, and normal-aging SAMR1 mice were used as the control group. The model mice were randomly divided into three groups: a model group, high-dose Res group (40mg/kg, intraperitoneal (ip)), and low-dose Res group (20mg/kg, ip). After receiving medication for 15 days, the mice were subjected to the water maze test to assess their spatial discrimination. The spectrophotometric method was used to detect the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) as well as the malondialdehyde (MDA) content. Quantitative PCR (q-PCR) was used to detect SOD, GSH-Px, CAT, and heme oxygenase-1 (HO-1) mRNA level changes. Western blot analysis detected HO-1 and Nrf2 protein expression. Second, we researched the effect of Res on the estrogen level in the SAMP8 model mice. The model mice were randomly divided into four groups: a model group, estrogen replacement group (0.28 mg/kg, intramuscular (im), estradiol benzoate), high-dose Res group (5 mg/kg, im), and low-dose Res group (2.5 mg/kg, im). The mice were injected, once every three days, for 5 weeks. Q-PCR was used to detect brain tissue mRNA expression changes. Western blot analysis detected ERα, ERβ, and ChAT protein expression. An enzyme-linked immunosorbent assay (ELISA) kit was used to detect the expression of E2 and amyloid β protein (Aβ) in brain tissue. Results. Compared with the control treatment, Res could improve the spatial abilities of the mice to a certain extent and also increase the expression of SOD, GSH-Px, CAT, and HO-1 at the mRNA level (P<0.05). In addition, enhanced SOD, GSH-Px, and CAT activities and HO-1 protein levels and decreased MDA content (P<0.05) were detected in the brain tissue of the Res-treated mice. The cytoplasmic Nrf2 content in the Res-treated mice was also decreased while the nuclear Nrf2 content and the nuclear translation rate of Nrf2 were increased (P<0.05). Res could decrease the expression of ERβ in the brain tissue at the mRNA and protein levels and the expression of Aβ in the brain tissue at the protein level. Res could also increase the mRNA and protein expression of ERα and ChAT and the protein expression of estradiol in the brain tissue. Conclusion. Res can increase the antioxidant capacity of AD models through the Nrf2/HO-1 signaling pathway. In addition, Res can enhance estrogen levels in an AD model. These findings provide a new idea for the treatment of AD.

Dexmedetomidine protects human renal tubular epithelial HK-2 cells against hypoxia/reoxygenation injury by inactivating endoplasmic reticulum stress pathway

2019 ◽  
Author(s):  
Mingyu Zhai ◽  
Mingming Han ◽  
Xiang Huang ◽  
Fang Kang ◽  
Chengwei Yang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Western Blot ◽  
Cell Viability ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Control Group ◽  
Sod Activity ◽  
Renal Tubular ◽  
Hypoxia Reoxygenation

Abstract Background: The study was aimed to explore the effects and potential mechanisms of Dexmedetomidine (Dex) on hypoxia/reoxygenation (H/R) injury in human renal tubular epithelial HK-2 cells. Methods: Human renal tubular epithelial HK-2 cells were divided into four groups: control group, Dex group, H/R group, and Dex + H/R group. After treatment, cell viability rate and cell apoptosis rate were measured by MTT assay and flow cytometry, respectively. Afterwards, the expressions of Hypoxia-inducible factor 1 (HIF-1α), glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), caspase-12 and cleaved caspase-3 were determined by western blot. Malondialdehyde (MDA) concentration and Superoxide Dismutase (SOD) activity were determined by assay kits. Results: Compared with control group, the cell viability rate was decreased and cell apoptotic was increased in H/R group. Besides, cell viability rate was increased, and cell apoptotic rate of HK-2 cells was decreased in Dex + H/R group, compared with H/R group. Western blot analysis showed that the expression of HIF-1α was up-regulated, and the expressions of GRP78, CHOP, capase-12 and cleaved caspase-3 were down-regulated in Dex + H/R group. In addition, the concentrations of MDA in Dex + H/R group and H/R group were 1.68 ± 0.22 nmol/mgprot and 0.85 ± 0.16 nmol/mgprot, which showed a 49.4% decrease in Dex + H/R group. However, after Dex treatment, the SOD activity was rose to 121 ± 11 U/L, which was more than twice larger than that in H/R group (57 ± 10 U/L). Conclusions: Dex could inhibit cell apoptosis by up-regulating the expression of HIF-1α, reducing endoplasmic reticulum stress and regulating oxidative stress, thus ameliorating the H/R injury.

The Study of Interference with Ruyanneixiao Cream on Hemorheology and Mammary Microcirculation of Mammary Precancer Rats

2012 ◽  
Vol 554-556 ◽  
pp. 1789-1793
Author(s):  
Gui Juan Zhang ◽  
De Hui Li ◽  
Rui Liao ◽  
Bi Zhu Tan ◽  
Yu Bin Liu ◽  
...  
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Plasma Viscosity ◽  
Control Group ◽  
High Dose ◽  
Model Group ◽  
Blank Control Group ◽  
Whole Blood Viscosity ◽  
Sd Rats ◽  
The Status

Objective: to probe the interference of Ruyanneixiao cream for hemorheology and mammary microcirculation of mammary precancer rats. Methods: 48 virginal female SD rats were randomly allocated into 6 groups, A: Blank control group (8); B: Mammary precancer model group (8); C: Tamoxifen (TAM) group (8); D: High dose group of Ruyanneixiao cream (8); E: Middle dose group of Ruyanneixiao cream (8); F: Low dose group of Ruyanneixiao cream (8). The changes of hemorheology and mammary microcirculation were recorded when the rats were executed after 60d. Result: compared with the Blank control group, the whole blood viscosity and plasma viscosity of mammary precancer model group was higher (P<0.05) and the perfusion of mammary microcirculation was lower (P<0.01). Compared with mammary precancer model group, the hemorheological parameters and perfusion of mammary microcirculation of each dose group of Ruyanneixiao cream were improved (P<0.05). Conclusion: Ruyanneixiao cream can improve the status of hemorheology, increase the perfusion of mammary microcirculation. And it may be one of mechanism to treat and prevent mammary precancer disease.

Acetaminophen: Neonatal hepatotoxicity due to late pregnancy exposure

1987 ◽  
Vol 45 ◽  
pp. 718-719
Author(s):  
G.A. Miranda ◽  
M.A. Arroyo ◽  
C.A. Lucio ◽  
M. Mongeotti ◽  
S.S. Poolsawat
Keyword(s):  
Low Dose ◽  
Fetal Liver ◽  
Late Pregnancy ◽  
Toxic Chemicals ◽  
Control Group ◽  
High Dose ◽  
Over The Counter ◽  
Liver And Kidney ◽  
Neonatal Liver ◽  
Childbearing Women

Exposure to drugs and toxic chemicals, during late pregnancy, is a common occurrence in childbearing women. Some studies have reported that more than 90% of pregnant women use at least 1 prescription; of this, 60% used more than one. Another study indicated that 80% of the consumed drugs were not prescribed, and of this figure, 95% were “over-the-counter” drugs. Acetaminophen, the safest of all over-the-counter drugs, has been reported to induce fetal liver necrosis in man and animals and to have abortifacient and embryocidal action in mice. This study examines the degree to which acetaminophen affects the neonatal liver and kidney, when a fatty diet is simultaneously fed to the mother during late pregnancy.Timed Swiss Webster female mice were gavaged during late pregnancy (days 16-19) with fat suspended acetaminophen at a high dose, HD = 84.50 mg/kg, and a low dose, LD = 42.25 mg/kg; a control group received fat alone.

Variations in the Lipid Profile of Patients with Chronic Renal Failure, Treated with Folic Acid

2003 ◽  
Vol 73 (3) ◽  
pp. 215-220 ◽  
Author(s):  
de Gómez Dumm ◽  
Giammona ◽  
Touceda
Keyword(s):  
Renal Failure ◽  
Folic Acid ◽  
Chronic Renal Failure ◽  
Density Lipoprotein ◽  
Plasma Homocysteine ◽  
Lipid Profiles ◽  
Erythrocyte Membranes ◽  
Favorable Effect ◽  
High Dose ◽  
Acid Therapy

Dyslipidemia and increases in plasma homocysteine usually occur at end-stage renal disease; both are recognized as risk factors for atherosclerosis. Folate administration reduces homocysteine concentration. In this study we determined the effect of a high dose of folic acid (40 mg intravenous injection three times a week) on plasma and red blood cell lipid profiles in twelve chronic renal failure patients on regular hemodialysis. Fasting blood samples were taken at the beginning of the study (baseline) and after 21, 42, and 64 days of treatment. Folic acid supplementation decreased plasma homocysteine. Plasma triglyceride levels decreased whereas polyunsaturated fatty acid values increased after 21 days; then they returned to baseline levels at the end of treatment. Total cholesterol and low-density lipoprotein (LDL) cholesterol were higher than those of the baseline during all the study, whereas high-density lipoprotein (HDL) cholesterol was reduced. In erythrocyte membranes, folic acid therapy enhanced cholesterol/phospholipid ratios and the fluorescence anisotropy of diphenyl-hexatriene. We conclude that large doses of folic acid produce a favorable effect, reducing plasma homocysteine levels and protecting patients from atherosclerosis. However, as this therapy induces significant alterations in both plasma and erythrocyte membrane lipid profiles, plasma lipid values should be controlled throughout the treatment of patients with renal failure.

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