The Effects of L-Arginine on Liver Damage in Experimental Acute Cholestasis an Immunohistochemical Study

Obstructive jaundice damages critical functions in the liver. Nitric oxide modulation would influence liver damage induced by biliary obstruction, and little is known about it Acute cholestasis was induced by bile duct ligation (BDL) in two groups of male Sprague-Dawley rats. L-Arginine or serum physiologic was administered to treatment and control group. Histopathological and immunohistochemical iNOS expression was investigated in hepatic tissue. Plasma enzyme activities were increased in acute cholestasis, and that L-arginine treatment partially but significantly prevented the elevation of these markers of liver damage (P< .05). Also histopathology scoring showed that the liver injury was prevented and immunohistochemical iNOS activity was increased significantly in L-arginine group (P< .05). This study shows that, after 7 days of biliary obstruction, liver damage is well established and exogenous L-arginine treatment partially but significantly prevented the liver injury in acute cholestasis.

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Synergistic suppression of pre-perfusion of donor livers with recipient serum and cobra venom factor treatment on hyperacute rejection following liver xenotransplantation

Acta Cirurgica Brasileira ◽

10.1590/s0102-86502012000500004 ◽

2012 ◽

Vol 27 (5) ◽

pp. 301-305 ◽

Cited By ~ 1

Author(s):

Baohua Zhu ◽

Chuanming Tong ◽

Weitao Guo ◽

Rong Pu ◽

Guoping Zhang ◽

...

Keyword(s):

Survival Time ◽

Hyperacute Rejection ◽

Cobra Venom ◽

Control Group ◽

Sprague Dawley ◽

Donor Liver ◽

Cobra Venom Factor ◽

Sd Rats ◽

Sprague Dawley Rats ◽

And Control

PURPOSE: To investigate synergistic suppression of donor liver pre-perfusion with recipient serum (RS) and cobra venom factor (CVF) treatment on hyperacute rejection (HAR) following liver xenotransplantation. METHODS: Guinea-pigs (GP, n=24) and Sprague-Dawley rats (SD, n=24) were recruited. Before transplantation, serum was collected from SD rats and used for preparation of inactivated complements. GP and SD rats were randomly assigned into four groups (n=6), respectively: RS group, CVF group, RS+CVF group and control group. Orthotopic liver xenotransplantation was performed with modified two-cuff technique. The survival time and liver function of recipients, morphological and pathological changes in rat livers were investigated. RESULTS: There was no piebald like change in the recipient livers in all experiment groups. The survival time of recipients in all experiment groups was longer than that in control group (p<0.05). Moreover, the survival time in the RS+CVF group was markedly longer than that in the RS group (p<0.01) and CVF group (p<0.05). The serum ALT level in all experiment groups were lower than that in the control group (p<0.05). Furthermore, the ALT level in the RS+CVF group was significantly lower than that in the CVF group (p<0.05) and RS group (p<0.01). The histological damages were significantly improved when compared with the control group, and the histological damages in the RS+CVF group were milder than those in the remaining groups (p<0.05) CONCLUSION: Pre-perfusion of donor liver with recipient serum and cobra venom factor treatment can exert synergistic suppressive effects on the hyperacute rejection following liver xenotransplantation.

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Experimental Study of the Effects of Hypoxia Simulator on Osteointegration of Titanium Prosthesis in Osteoporotic Rats

10.21203/rs.3.rs-379490/v1 ◽

2021 ◽

Author(s):

Jiangfeng Liu ◽

Huijun Kang ◽

Jiangfeng Lu ◽

Yike Dai ◽

Fei Wang

Keyword(s):

Control Group ◽

Osteoporotic Bone ◽

Mrna Levels ◽

Micro Ct ◽

Sprague Dawley ◽

Pull Out ◽

Sprague Dawley Rats ◽

Bone To Implant Contact ◽

Polymerase Chain ◽

And Control

Abstract Purpose: Poor osseointegration is the key reason for implant failure after arthroplasty, whether in osteoporotic or normal bone conditions. To date, osseointegration remains a major challenge. Recent studies have shown that deferoxamine(DFO) can accelerate osteogenesis by activation of the hypoxia signal pathway. The purpose of this study is to test the following hypothesis: after knee replacement, intra-articular injection of DFO will promote osteogenesis and osseointegration with titanium prosthesis in the bones of osteoporotic rats.Materials and Methods: 90 female sprague-dawley rats were used for the experiment. Ovariectomy and knee arthroplasty were performed. Then, the rats were randomly divided into DFO and control group(n=40 per group). The two groups were treated by intraarticular injection of DFO and saline respectively. After 2 weeks, polymerase chain reaction(PCR) and immunohistochemistry were used to evaluate the levels of HIF-1a, VEGF and CD31. After 12 weeks, the specimens were examined by micro CT, biomechanics and histopathology to evaluate osteogenesis and osseointegration.Results: The results of PCR showed mRNA levels of VEGF and CD31 in DFO group were significantly higher than those in control group. The immunohistochemistry results indicated positive cell expressions of HIF-1a, VEGF and CD31 in DFO group were also higher. Compared to control group, the microCT parameters of BMD, BV/TV, TB.N, TB.Th were significantly higher. The maximal pull-out force and the bone-to-implant contact (BIC) value were also higher . Conclusions: The local administration of DFO which is used to activate HIF-1a signaling pathway can promote osteogenesis and osseointegration with the prosthesis in osteoporotic bone.

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Possible Association Between DHEA and PKCε in Hepatic Encephalopathy Amelioration: A Pilot Study

Frontiers in Veterinary Science ◽

10.3389/fvets.2021.695375 ◽

2021 ◽

Vol 8 ◽

Author(s):

Alessandro Di Cerbo ◽

Luca Roncati ◽

Carlotta Marini ◽

Gianluca Carnevale ◽

Manuela Zavatti ◽

...

Keyword(s):

Hepatic Encephalopathy ◽

Neuroprotective Effect ◽

Brain Area ◽

Control Group ◽

Sprague Dawley ◽

Kinase C ◽

Sprague Dawley Rats ◽

Protein Kinase C Epsilon ◽

Neuronal Functions ◽

And Control

Objective: Hepatic encephalopathy (HE) is a neuropsychiatric syndrome caused by liver failure and by an impaired neurotransmission and neurological function caused by hyperammonemia (HA). HE, in turn, decreases the phosphorylation of protein kinase C epsilon (PKCε), contributing to the impairment of neuronal functions. Dehydroepiandrosterone (DHEA) exerts a neuroprotective effect by increasing the GABAergic tone through GABAA receptor stimulation. Therefore, we investigated the protective effect of DHEA in an animal model of HE, and the possible modulation of PKCε expression in different brain area.Methods: Fulminant hepatic failure was induced in 18 male, Sprague–Dawley rats by i.p. administration of 3 g/kg D-galactosamine, and after 30 min, a group of animals received a subcutaneous injection of 25 mg/kg (DHEA) repeated twice a day (3 days). Exploratory behavior and general activity were evaluated 24 h and 48 h after the treatments by the open field test. Then, brain cortex and cerebellum were used for immunoblotting analysis of PKCε level.Results: DHEA administration showed a significant improvement of locomotor activity both 24 and 48 h after D-galactosamine treatment (****p < 0.0001) but did not ameliorate liver parenchymal degeneration. Western blot analysis revealed a reduced immunoreactivity of PKCε (*p < 0.05) following D-galactosamine treatment in rat cortex and cerebellum. After the addition of DHEA, PKCε increased in the cortex in comparison with the D-galactosamine-treated (***p < 0.001) and control group (*p < 0.05), but decreased in the cerebellum (*p < 0.05) with respect to the control group. PKCε decreased after treatment with NH4Cl alone and in combination with DHEA in both cerebellum and cortex (****p < 0.0001). MTS assay demonstrated the synergistic neurotoxic action of NH4Cl and glutamate pretreatment in cerebellum and cortex along with an increased cell survival after DHEA pretreatment, which was significant only in the cerebellum (*p < 0.05).Conclusion: An association between the DHEA-mediated increase of PKCε expression and the improvement of comatose symptoms was observed. PKCε activation and expression in the brain could inhibit GABA-ergic tone counteracting HE symptoms. In addition, DHEA seemed to ameliorate the symptoms of HE and to increase the expression of PKCε in cortex and cerebellum.

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Cell Activation and Function Alteration in Rat Livers Induced by Repeated Aluminum Oxide Nanoparticles Exposure

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.486.75 ◽

2012 ◽

Vol 486 ◽

pp. 75-79

Author(s):

Xiao Bo Li ◽

Hao Zheng ◽

Ran Liu ◽

Ge Yu Liang

Keyword(s):

Aluminum Oxide ◽

Cell Activation ◽

Control Group ◽

Oxide Nanoparticles ◽

Sprague Dawley ◽

Aluminum Oxide Nanoparticles ◽

Liver Macrophages ◽

Sprague Dawley Rats ◽

And Function ◽

And Control

Liver is a major target of nanoparticles accumulation. Here we have analyzed the liver function and activation of liver macrophages, which are sensitive to alteration of liver internal environment after repeated exposure to aluminum oxide nanoparticles. Sprague-Dawley rats where intraperitoneally injected very two days for 60 dyas with aluminum oxide nanoparticles (50mg/kg), non-nanoaluminum oxide (50mg/kg) and saline. After 60 days exposure, the concentrations of alanine aminotransferase and aspartic transaminase in plasma were significantly higher in nanoaluminum oxide group than non-nanoaluminum oxide and control groups. The number of ED-1+and GFAP+cells in liver of nanoaluminum oxide and non-nanoaluminum oxide groups increased significantly than control group. Compared with non-nanoaluminum oxide, aluminum oxide nanoparticles display potential adverse effects on the hypatocytes and biliary tract of rat liver and less stimulus to macrophages in liver than non-nanoaluminum oxide. It is suggested that part aluminum oxide nanoparticles avoided from phagocytosis by liver macrophages. The effects of aluminum oxide nanoparticles exposure should be assessed for its potential hepatic toxicology.

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Chronic Variable Stress Induces Hepatic Fe(II) Deposition by Up-Regulating ZIP14 Expression via miR-181 Family Pathway in Rats

Biology ◽

10.3390/biology10070653 ◽

2021 ◽

Vol 10 (7) ◽

pp. 653

Author(s):

Shuxia Jiang ◽

Taining Guo ◽

Shihui Guo ◽

Jiang Gao ◽

Yingdong Ni ◽

...

Keyword(s):

Body Weight ◽

Liver Damage ◽

Weight Ratio ◽

Luciferase Reporter ◽

Control Group ◽

Hepatic Iron ◽

Sprague Dawley ◽

Reporter System ◽

Sprague Dawley Rats ◽

Chronic Variable Stress

It is well-known that hepatic iron dysregulation, which is harmful to health, can be caused by stress. The aim of the study was to evaluate chronic variable stress (CVS) on liver damage, hepatic ferrous iron deposition and its molecular regulatory mechanism in rats. Sprague Dawley rats at seven weeks of age were randomly divided into two groups: a control group (Con) and a CVS group. CVS reduces body weight, but increases the liver-to-body weight ratio. The exposure of rats to CVS increased plasma aspartate aminotransferase (AST), alkaline phosphatase (ALP) and hepatic malondialdehyde (MDA) levels, but decreased glutathione peroxidase (GSH-Px) activity, resulting in liver damage. CVS lowered the total amount of hepatic iron content, but induced hepatic Fe(II) accumulation. CVS up-regulated the expression of transferrin receptor 1 (TFR1) and ZRT/IRT-like protein 14 (ZIP14), but down-regulated ferritin and miR-181 family members. In addition, miR-181 family expression was found to regulate ZIP14 expression in HEK-293T cells by the dual-luciferase reporter system. These results indicate that CVS results in liver damage and induces hepatic Fe(II) accumulation, which is closely associated with the up-regulation of ZIP14 expression via the miR-181 family pathway.

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Supplementation with Fermented Rice Bran Attenuates Muscle Atrophy in a Diabetic Rat Model

Nutrients ◽

10.3390/nu12082409 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2409 ◽

Cited By ~ 1

Author(s):

Tubagus Bahtiar Rusbana ◽

Afifah Zahra Agista ◽

Wahyu Dwi Saputra ◽

Yusuke Ohsaki ◽

Kouichi Watanabe ◽

...

Keyword(s):

Muscle Atrophy ◽

Rice Bran ◽

Rat Model ◽

Muscle Size ◽

Diabetic Rat ◽

Control Group ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

And Control ◽

Diabetic Rat Model

Fermented rice bran (FRB), a prospective supplement, has been proven to ameliorate certain medical conditions. However, its nutraceutical effect on muscle atrophy has never been investigated. The present study aimed to evaluate the effect of FRB on muscle atrophy in a streptozotocin (STZ)-induced diabetic rat model. Three groups of Sprague-Dawley rats, namely the control, STZ, and FRB groups, were treated as follows. The diabetic groups (STZ and FRB) were injected intraperitoneally with STZ (40 mg/kg BW), whereas the control group was injected with the vehicle. The STZ and control groups were fed the AIN93M diet, and the FRB group was fed 10% of FRB based on the AIN93M diet. The diabetic groups had reduced muscle size compared to the control group; however, these changes were alleviated in the FRB group. Moreover, the FRB group had a significantly lower expression of FBXO32/Atrogin-1 and TRIM63/MuRF1 (p < 0.05) due to blocked NF-κB activation. In conclusion, the anti-inflammatory effect of FRB may be beneficial for ameliorating muscle atrophy in diabetic conditions.

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Chilean Strawberry Consumption Protects against LPS-Induced Liver Injury by Anti-Inflammatory and Antioxidant Capability in Sprague-Dawley Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/320136 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 12

Author(s):

Sebastian Molinett ◽

Francisca Nuñez ◽

María Alejandra Moya-León ◽

Jessica Zúñiga-Hernández

Keyword(s):

Liver Injury ◽

Aqueous Extract ◽

Inflammatory Responses ◽

Animal Health ◽

Antioxidant Properties ◽

Serum Levels ◽

Control Group ◽

Sprague Dawley ◽

Sprague Dawley Rats

The Chilean strawberry fruit has high content of antioxidants and polyphenols. Previous studies evidenced antioxidant properties byin vitromethods. However, the antioxidant effect and its impact as functional food on animal health have not been evaluated. In this study, rats were fed with a Chilean strawberry aqueous extract (4 g/kg of animal per day) and then subjected to LPS-induced liver injury (5 mg/kg). Transaminases and histological studies revealed a reduction in liver injury in rats fed with strawberry aqueous extract compared with the control group. Additionally, white strawberry supplementation significantly reduced the serum levels and gene expression of TNF-α, IL-6, and IL-1βcytokines compared with nonsupplemented rats. The level of F2-isoprostanes and GSH/GSSG indicated a reduction in liver oxidative stress by the consumption of strawberry aqueous extract. Altogether, the evidence suggests that dietary supplementation of rats with a Chilean white strawberry aqueous extract favours the normalization of oxidative and inflammatory responses after a liver injury induced by LPS.

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Extrahepatic angiogenesis hinders recovery of portal hypertension and collaterals in rats with cirrhosis resolution

Clinical Science ◽

10.1042/cs20171370 ◽

2018 ◽

Vol 132 (6) ◽

pp. 669-683 ◽

Cited By ~ 2

Author(s):

Shao-Jung Hsu ◽

Ming-Hung Tsai ◽

Ching-Chih Chang ◽

Yu-Hsin Hsieh ◽

Hui-Chun Huang ◽

...

Keyword(s):

Portal Hypertension ◽

Portal Pressure ◽

Treatment Strategies ◽

Vascular Complications ◽

Control Group ◽

No Production ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Duct Ligation ◽

Window Area

Liver cirrhosis is characterized by portal hypertension. However, the alteration of portal hypertension-related derangements during cirrhosis resolution is not well known. The present study aimed to establish animal models with cirrhosis resolution and to investigate the relevant changes during this process. Male Sprague–Dawley rats were applied. In reverse thioacetamide (rTAA) model, rats were randomly allocated into four groups with control, thioacetamide (TAA) cirrhosis and rTAA groups that discontinued TAA for 4 or 8 weeks after cirrhosis induction. In reverse bile duct ligation (rBDL) model, rats received choledochoduodenal shunt surgery upon the establishment of cirrhosis and 4, 8, or 16 weeks were allowed after the surgery. At the end, portal hypertension-related parameters were evaluated. Cirrhosis resolution was observed in rTAA groups. Portal pressure (PP) decreased after cirrhosis resolution but remained higher than control group (control, TAA, rTAA4, rTAA8 (mmHg): 5.4 ± 0.3, 12.9 ± 0.3, 8.6 ± 0.4, 7.6 ± 0.6). Further survey found the increased splanchnic blood flow did not reduce during cirrhosis resolution. The extrahepatic pathological angiogenesis was not ameliorated (% of mesenteric window area: 1.2 ± 0.3, 7.3 ± 1.1, 8.3 ± 1.0, 11.3 ± 2.7). In collateral system, the shunting degree reduced while the vessels structure remained. The vascular contractility of all systems and nitric oxide (NO) production were normalized. In rBDL series, PP decreased in rBDL16 groups but the extrahepatic angiogenesis persisted. In conclusion, cirrhosis resolution attenuates but not completely normalizes portal hypertension because of persistently high splanchnic inflow and angiogenesis. In clinical setting, vascular complications such as varices could persist after cirrhosis resolution and further investigation to define the follow-up and treatment strategies is anticipated.

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Methane-Rich Saline Counteracts Cholestasis-Induced Liver Damage via Regulating the TLR4/NF-κB/NLRP3 Inflammasome Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/6565283 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13 ◽

Cited By ~ 4

Author(s):

Zeyu Li ◽

Dongdong Chen ◽

Yifan Jia ◽

Yang Feng ◽

Cong Wang ◽

...

Keyword(s):

Liver Fibrosis ◽

Liver Injury ◽

Inflammatory Cells ◽

Protective Mechanism ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Duct Ligation ◽

Associated Proteins ◽

Anti Inflammatory ◽

Cholestatic Liver Injury

Cholestatic liver injury, due to obstruction of the biliary tract or genetic defects, is often accompanied by progressive inflammation and liver fibrosis. Methane-rich saline (MRS) has anti-inflammatory properties. However, whether MRS can provide protective effect in cholestatic liver injury is still unclear. In this study, Sprague-Dawley rats received bile duct ligation (BDL) to generate a cholestatic model followed by MRS treatment (10 mL/kg, ip treatment) every 12 h after the operation to explore the potential protective mechanism of MRS in cholestatic liver injury. We found that MRS effectively improved liver function, alleviated liver pathological damage, and localized infiltration of inflammatory cells. MRS treatment decreased the expression of hepatic fibrosis-associated proteins to alleviate liver fibrosis. Furthermore, MRS treatment suppressed the TLR4/NF-κB pathway and further reduced the levels of proinflammatory factors. Downregulation of NF-κB subsequently reduced the NLRP3 expression to inhibit pyroptosis. Our data indicated that methane treatment prevented cholestatic liver injury via anti-inflammatory properties that involved the TLR4/NF-κB/NLRP3 signaling pathway.

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Inhibition of Toll-like receptor 4 suppresses liver injury induced by biliary obstruction and subsequent intraportal lipopolysaccharide injection

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00366.2013 ◽

2014 ◽

Vol 306 (3) ◽

pp. G244-G252 ◽

Cited By ~ 14

Author(s):

Shingo Oya ◽

Yukihiro Yokoyama ◽

Toshio Kokuryo ◽

Masanori Uno ◽

Kohei Yamauchi ◽

...

Keyword(s):

Liver Injury ◽

Liver Damage ◽

Kupffer Cells ◽

Biliary Drainage ◽

Biliary Obstruction ◽

Sham Group ◽

Sham Operation ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Duct Ligation

The objective of this study was to elucidate the role of Toll-like receptor 4 (TLR4) in liver injury induced by biliary obstruction and subsequent intraportal lipopolysaccharide (LPS) infusion in rats. Biliary obstruction often leads to the development of bacterial translocation. Rats were subjected to either a sham operation (Sham group) or bile duct ligation for 7 days (BDL group). Seven days after each operation, LPS (0.5 μg) was injected through the ileocecal vein. In other experiments, rats that had undergone BDL were pretreated, before LPS challenge, with internal biliary drainage (Drainage group); intravenous TAK-242, a TLR4 inhibitor (TAK group); or intravenous GdCl3, a Kupffer cell deactivator (GdCl3group). The expression of the TLR4 protein and the number of Kupffer cells in the liver were significantly increased in the BDL group compared with the Sham group. These changes were normalized after biliary drainage. The expression of TLR4 colocalized with Kupffer cells, which was confirmed by double immunostaining. Serum levels of liver enzymes and proinflammatory cytokines after intraportal LPS injection were significantly higher in the BDL group than in the Sham group. However, pretreatment with TAK-242 or GdCl3strongly attenuated these changes to levels similar to those seen with biliary drainage. These results imply that blocking TLR4 signaling effectively attenuates liver damage to the same level as that observed with biliary drainage in rats with BDL and subsequent intraportal LPS infusion. TAK-242 treatment may be used for patients who are susceptible to liver damage by biliary obstruction and endotoxemia.

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