Is there any effect of renal failure on the hepatic regeneration capacity following partial hepatectomy in rats?

The effects of renal dysfunction on liver regeneration capacity have not been fully elucidated before, although many patients with renal failure are subjected to hepatectomy due to hepatobiliary diseases. In this study, we sought to determine the effects of renal dysfunction on the hepatic regeneration capacity using rat chronic renal failure model. After establishing chronic renal failure (CRF group) by semi-total renal resection, the rats were subjected to 70% partial hepatectomy (PHx). Rats without renal failure were used as control (Sham group). The hepatic regeneration rate, histology of the liver, clearance of indocyanine green into the bile, and the expression of hepatic regeneration-associated genes in the liver were evaluated. The hepatic regeneration rate was lower in CRF group as compared to Sham group on day 1 after PHx. Mitotic index evaluated by histologic examination on day 1 after PHx was also significantly lower in CRF group. However, no difference in these indices was observed on day 2 and 7 between Sham and CRF. Indocyanine green clearance rate was almost identical between Sham and CRF on day 7 following PHx. The baseline expressions of the hepatic regeneration-associated genes, such as IL-6, TNF-alpha, HGF, c-fos, and c-jun, in the liver of CRF were significantly lower than those of Sham. However, the rate of upregulation of these genes was not significantly different between Sham and CRF. These results clearly demonstrate that the renal dysfunction, although initially delays the onset, does not suppress the total hepatic regeneration capacity following partial hepatectomy. The function of the regenerated liver on day 7 after PHx also was not different. Our results provide a possibility that the hepatectomy can be indicated even for the patient with a chronic renal failure.     

Grey-Scale Ultrasound in the Imaging of Urinary Tract Disease

Grey-scale ultrasound defines smaller renal lesions that had previously been appreciated and is able to define associated lesions of the liver such as metastases and cysts. The appropriate technique to delineate the normal anatomy of the kidney is described. Ultrasound plays a central role in the identification and characterization of renal mass lesions thus leading to appropriate further work up. In renal transplant evaluation ultrasound is useful as a complementary modality to other imaging studies permitting the recognition of pelvic fluid collections, rejection, and hydronephrosis. Specific findings are present in renal abscess, perirenal abscess, and in several of the renal cystic diseases. Adrenal lesions can be identified and clarified. In the lower urinary tract, ultrasound can identify bladder and prostatic tumors.Ultrasound provides a rapid, safe and non-invasive modality which is complementary to other imaging techniques in the diagnosis of urinary tract disease.     

眼镜蛇咬伤患者早期肝肾功能、心肌酶的变化

目的观察眼镜蛇咬伤患者早期肝、肾功能及心肌酶的改变,以探讨其临床意义。方法对30例眼镜蛇咬伤患者入院时即抽取静脉血2.0 ml,分离血清,按常规方法行肝、肾功能及心肌酶的测定,并与健康体检者进行比较。结果与对照组比较,眼镜蛇咬伤患者早期肝功能及心肌酶指标显著升高(P0.05);肾功能检测结果差异无显著性(P0.05)。结论通过对眼镜蛇咬伤患者肝、肾功能及心肌酶的测定,了解患者肝脏、肾脏、心肌损害程度,对指导临床治疗具有一定意义。     

Alteration of renal functional, oxidative stress and inflammatory indices following hepatic ischemia-reperfusion

Liver ischemia/reperfusion (IR) injury is a complex phenomenon that may cause local as well as remote organ injuries. Reactive oxygen species (ROS) along with many pro- and anti- inflammatory cytokines are implicated in the development of organ injury. The renal functional, histological, oxidative stress and inflammatory indices were studied during a short and a longer period of liver IR. Rats were subjected to either sham operation or 90 min partial liver ischemia followed by 4 or 24 h of reperfusion. Serum ALT, AST, ALK and LDH levels, BUN and creatinine, renal MDA level, SOD and catalase activities were evaluated as well as serum IL-6 and IL-10 concentrations along with renal histological evaluation. Ninety minutes liver ischemia /4 h reperfusion caused an increase in BUN and renal MDA levels and a decrease in SOD and catalase activities. It also caused an increase in serum IL-6 and IL-10 levels. 24 h liver reperfusion resulted in a reduction in BUN levels and lower oxidative damages demonstrated by a decrease in renal MDA levels and an increase in renal SOD and catalase activities comparing to 4 h reperfusion group. Evaluations indicated improvement in histology such as less cytoplasmic vacuolation and lower tubular debris. Serum inflammatory indices (IL-6 and IL-10 levels) were also reduced. This study showed that liver IR damage causes renal injury including functional, inflammatory and oxidative status changes. The remote kidney damage was then improved by continuing reperfusion from 4 to 24 h.     

Regulation of epithelial cell morphology and functions approaching to more in vivo-like by modifying polyethylene glycol on polysulfone membranes

Cytocompatibility is critically important in design of biomaterials for application in tissue engineering. However, the currently well-accepted "cytocompatible" biomaterials are those which promote cells to sustain good attachment/spreading. The cells on such materials usually lack the self-assembled cell morphology and high cell functions as in vivo. In our view, biomaterials that can promote the ability of cells to self-assemble and demonstrate cell-specific functions would be cytocompatible. This paper examined the interaction of polyethylene glycol (PEG) modified polysulfone (PSf) membranes with four epithelial cell types (primary liver cells, a liver tumor cell line, and two renal tubular cell lines). Our results show that PSf membranes modified with proper PEG promoted the aggregation of both liver and renal cells, but the liver cells more easily formed aggregates than the renal tubular cells. The culture on PEG-modified PSf membranes also enhanced cell-specific functions. In particular, the cells cultured on F127 membranes with the proper PEG content mimicked the in vivo ultrastructure of liver cells or renal tubules cells and displayed the highest cell functions. Gene expression data for adhesion proteins suggest that the PEG modification impaired cell-membrane interactions and increased cell-cell interactions, thus facilitating cell self-assembly. In conclusion, PEG-modified membrane could be a cytocompatible material which regulates the morphology and functions of epithelial cells in mimicking cell performance in vivo.     

HO-1 在肝肾疾病中的作用研究进展

血红素氧合酶是血红素降解的限速酶,与酶解产物胆红素、CO-道,共同发挥着抗氧化、抗炎、抑制细胞凋亡、改善组织微循环等作用。血红素氧合酶1是血红素氧合酶的诱导型在脓毒血症、高血压、急性肺损伤等多种疾病中均呈现适应性诱导表达并产生相应的细胞保护作用在肝脏缺血再灌注损伤、肝硬化、肝衰竭、肝移植、急性肾损伤、移植肾损伤等疾病中也发挥着细胞保护作用。本文综述了近年来血红素氧合酶1在肝肾疾病中作用的研究进展,以期为未来治疗方法带来新突破。     

Alterations in the physicochemical properties of renal cortical membranes in rats with experimental cirrhosis of the liver.

Changes in the major component of renal cortical membranes as well as membrane fluidity and Na+, K+, ATPase activity have been studied in membranes from the renal cortex of rats with experimental liver cirrhosis, which show renal sodium and water retention, and in normal animals. Rats with cirrhosis of the liver show a decrease in cholesterol, phospholipid and protein content, without changes in cholesterol/phospholipid molar ratio. In addition there is a small decrease in 14:0 and 18:2 and an increase in 20:4 content, without differences in unsaturation degree. Membrane fluidity was decreased in renal membranes from cirrhotic rats when compared with normal ones. Na+, K+, ATPase activity was higher in cirrhotic than in normal renal membranes could be related with the changes in renal water and electrolyte changes shown by cirrhotic rats.     

Signaling pathway factors expression in renal tissue of apoE-knockout mice

Abstract

Apolipoprotein E (apoE) is regarded as one of the major plasma lipoproteins, and it plays an important role in the transport and metabolism of lipids. apoE can be found in multiple tissues, such as liver, kidney, jejunum, urinary bladder, ileum, colon, brain, adrenal glands, lung, ovary, spleen, pancreas, and testis, etc. As a secreted protein, it plays an important role in the systemic lipoprotein metabolism and vascular wall homeostasis and in the pathogenesis of renal diseases. apoE-knockout (apoE(?/?)) mice is a classic model of atherosclerosis and renal diseases. However, no review summed up the signaling pathway factors expression in renal tissue of apoE-knockout mice. The literatures were searched extensively and this review was performed to review the signaling pathway factors expression in renal tissue of apoE-knockout mice.     

安南龟肝脏和肾脏的组织学观察

采用常规石蜡切片对安南龟的肝脏和肾脏进行了组织学观察。研究结果发现,肝脏分为3叶,肝实质内结缔组织少。肝脏由无数肝小叶构成,肝小叶分界不清。肝细胞为多角形的腺上皮细胞,细胞核圆球形,位于中央。胆小管沿着肝细胞索向肝小叶四周放射并连成细长的微细管道。肾脏由肾小体、颈段、近曲小管、中间段、远曲小管和收集管6部分构成,肾小体由肾小球和肾小囊组成,在肾小体附近可见致密斑样结构,未见髓袢结构。肾小球由盘曲的毛细血管构成。肾小囊是肾小管的起始端,由内、外两层壁层构成,内层与肾小球的毛细血管紧贴,外层为单层扁平上皮细胞。     

Benzoate modulates renal and extrarenal nitrogen flow: metabolic mechanisms.

The mechanism by which benzoate enhances total nitrogen excretion was investigated in-situ and in separated rat renal proximal tubules. Orally administered benzoate augmented NH4+, urea and hippurate excretion 2, 1.9 and 76 fold respectively, as compared to baseline for control. Hippurate had similar effects. Benzoate augmented renal blood flow, glutamine extraction and total NH4+ production. Arterio-venous concentration differences of glutamine, glutamate, and NH4+ across the kidney, liver and gut demonstrated an increase in glutamine uptake by the kidney despite reduced release and uptake by the liver and gut, respectively; glutamate release by the kidney and gut was increased; NH4+ handling was unchanged at these three organs. Studies in separated rat renal proximal tubules demonstrated that benzoate stimulated glutamine dependent ammonia-genesis by activation of gamma-glutamyltransferase, via the synthesis of hippurate. The results demonstrate that benzoate can modulate the interorgan partitioning of nitrogen metabolites across several organs, the net effect of which is physiologically expressed as enhanced NH4+ , urea and hippurate excretion.     

D-半乳糖致衰老模型大鼠肝肾功能和自由基代谢与中药的干预作用

目的观察D-半乳糖致衰老模型大鼠血糖血脂、肝肾功能和自由基代谢的变化,探讨中药的干预作用及其抗衰老的机制。方法大鼠每日皮下注射D-半乳糖,连续造模7周,建立大鼠衰老模型,造模同时,用抗衰老片和首乌延寿片进行干预,测定试验大鼠的血糖血脂、肝肾功能和SOD、MDA、Na＋-K＋-ATPase和Ca＋＋-Mg＋＋-ATPase等自由基代谢指标。结果造模7周后,模型对照组衰老大鼠TG、BUN明显升高（P〈0.05,P〈0.01）,AST、ALP、CREA呈上升趋势（P〉0.05）,肝、肾组织SOD活性明显降低（P〈0.05）,肾组织MDA含量明显升高（P〈0.05）,肝组织Na＋-K＋-ATPase和Ca＋＋-Mg＋＋-ATPase活性均显著降低（P〈0.05,P〈0.01）;给予抗衰老片和首乌延寿片后,衰老大鼠TG、AST、BUN、CREA和UA均显著降低（P〈0.05,P〈0.01）,肝、肾组织MDA含量显著降低（P〈0.05）,SOD活性显著升高（P〈0.05,P〈0.01）,肝组织Na＋-K＋-ATPase和Ca＋＋-Mg＋＋-ATPase活性均显著升高（P〈0.01）。结论D-半乳糖致衰老大鼠模型的血脂上升、肝肾功能异常和抗脂质过氧化的能力下降;给予抗衰老片和首乌延寿片后,可有效改善衰老大鼠的糖脂代谢和肝肾功能,提高肝肾组织的抗脂质过氧化的能力,提示中药的抗衰老作用可能与其抗氧化作用有关。     

Imaging Mass Spectrometry Reveals Acyl-Chain- and Region-Specific Sphingolipid Metabolism in the Kidneys of Sphingomyelin Synthase 2-Deficient Mice

Obesity was reported to cause kidney injury by excessive accumulation of sphingolipids such as sphingomyelin and ceramide. Sphingomyelin synthase 2 (SMS2) is an important enzyme for hepatic sphingolipid homeostasis and its dysfunction is considered to result in fatty liver disease. The expression of SMS2 is also high in the kidneys. However, the contribution of SMS2 on renal sphingolipid metabolism remains unclear. Imaging mass spectrometry is a powerful tool to visualize the distribution and provide quantitative data on lipids in tissue sections. Thus, in this study, we analyzed the effects of SMS2 deficiency on the distribution and concentration of sphingomyelins in the liver and kidneys of mice fed with a normal-diet or a high-fat-diet using imaging mass spectrometry and liquid chromatography/electrospray ionization-tandem mass spectrometry. Our study revealed that high-fat-diet increased C18–C22 sphingomyelins, but decreased C24-sphingomyelins, in the liver and kidneys of wild-type mice. By contrast, SMS2 deficiency decreased C18–C24 sphingomyelins in the liver. Although a similar trend was observed in the whole-kidneys, the effects were minor. Interestingly, imaging mass spectrometry revealed that sphingomyelin localization was specific to each acyl-chain length in the kidneys. Further, SMS2 deficiency mainly decreased C22-sphingomyelin in the renal medulla and C24-sphingomyelins in the renal cortex. Thus, imaging mass spectrometry can provide visual assessment of the contribution of SMS2 on acyl-chain- and region-specific sphingomyelin metabolism in the kidneys.     

Localization of the fructose 1,6-bisphosphatase at the nuclear periphery

The localization of fructose 1,6-bisphosphatase (D-Fru-1,6-P₂-1-phosphohydrolase, EC 3.1.3.11) in rat kidney and liver was determined immunohistochemically using a polyclonal antibody raised against the enzyme purified from pig kidney. The immunohistochemical analysis revealed that the bisphosphatase was preferentially localized in hepatocytes of the periportal region of the liver and was absent from the perivenous region. Fructose-1,6-bisphosphatase was also preferentially localized in the cortex of the kidney proximal tubules and was absent in the glomeruli, loops of Henle, collecting and distal tubules, and in the renal medulla. As indicated by immunocytochemistry using light microscopy and confirmed with the use of reflection confocal microscopy, the enzyme was preferentially localized in a perinuclear position in the liver and the renal cells. Subcellular fractionation studies followed by enzyme activity assays revealed that a majority of the cellular fructose-1,6-bisphosphatase activity was associated to subcellular particulate structures. Overall, the data support the concept of metabolic zonation in liver as well as in kidney, and establish the concept that the Fructose-1,6-bisphosphatase is a particulate enzyme that can not be considered a soluble enzyme in the classical sense. © 1996 Wiley-Liss, Inc.     

Dietary cadmium decreases lipid peroxidation in the liver and kidneys of the bank vole (Clethrionomys glareolus).

The effect of elevated levels of dietary cadmium on lipid peroxidation in the liver and kidneys of a small rodent, the bank vole, was determined in the present study. Males and females, aged 1 month, were given diets containing 0.40 and 80 mg Cd per kg; liver and kidneys were removed for TBA-RS as well as iron, copper, zinc, cadmium and metallothionein analyses at the end of 6 weeks. Dietary Cd significantly decreased the TBA-RS level in the liver and kidneys of both sexes; however, this effect appeared to be dose-dependent only for the male liver. The changes in hepatic and renal TBA-RS paralleled closely those of tissue iron. Copper concentration decreased significantly only in the male liver, while hepatic and renal zinc were not influenced by dietary Cd. The concentrations of Cd and metallothionein in the liver and kidneys increased significantly in a dose-dependent fashion. Regression analysis confirmed that TBA-RS in both organs correlated closely with iron. The data suggest that dietary Cd decreases hepatic and renal lipid peroxidation indirectly, through lowering the tissue iron concentration.     

Membrane lipid changes in erythrocytes, liver and kidney in acute and chronic experimental liver disease in rats

Lipid molecules in lipoprotein surfaces exchange with their counterparts in cell plasma membranes. In human or experimental liver disease, plasma lipoprotein surfaces are enriched in cholesterol and deficient in arachidonate; corresponding alterations occur in membrane lipids of erythrocytes. To determine whether similar changes take place in membranes of nucleated cells, the lipid content of plasma and of erythrocyte, liver and kidney membranes was measured in rats with acute (3-day) galactosamine-induced hepatitis or chronic (3-week) biliary obstruction. In both models of liver injury the cholesterol:phospholipid ratio in plasma and in erythrocytes was significantly increased (P less than 0.001). Although this ratio was also elevated in liver and kidney microsomes, only in liver microsomes of obstructed rats was the increase significant (P less than 0.001). However, the cholesterol:phospholipid ratio of kidney brush-border membranes, was significantly higher in bile-duct-ligated rats; presumably, compensating mechanisms limit cholesterol accumulation in intracellular membranes. Kidney brush-border membranes from obstructed rats were deficient in arachidonate as were plasma and erythrocytes. However, arachidonate levels were unchanged in kidney microsomes; renal delta 6-desaturase, the rate-limiting enzyme in the conversion of linoleic acid to arachidonic acid, was increased by 50% (P less than 0.001) and may have counteracted a reduced supply of exogenous lipoprotein arachidonate. We conclude that in experimental liver disease lipoprotein-induced lipid abnormalities can occur in renal membranes, although compensatory mechanisms may operate; the alterations seen, cholesterol accumulation and arachidonate depletion, would be expected to interfere with sodium transport and prostaglandin production, respectively. Our findings support the hypothesis that lipid abnormalities in kidney membranes contribute to the renal dysfunction which is a frequent complication of human liver disease.     

The fatty acid composition of the tissues of streptozotocin-diabetic rats

The authors studied acute changes in the fatty acid composition of the tissues of streptozotocin-diabetic rats. They found that streptozotocin diabetes led to changes in the total lipids fatty acid spectrum in serum and in tissues (liver, adipose tissue, renal cortex diaphragm). After only 7 days' diabetes there was an increase in the percentual proportion of saturated fatty acids and a decrease in the amount of polyene fatty acids in the serum and in all the above tissue of diabetic animals. Palmitic acid (16:0) participated in the increase in the proportion of saturated fatty acids in all the given tissues, while stearic acid (18:0) played a role in the increase in the renal cortex and the serum. Among the monoene acids, there was a drop in the proportion of palmitoleic acid (16:1) in the adipose tissue and serum and in the amount of oleic acid (18:1) in the renal cortex, liver and muscle. Linoleic acid (18:2) played a role in the decrease in the proportion of polyene acids in all the given tissues and the serum, while arachidonic acid (20:4) was involved in the drop in the renal cortex, liver and muscle. The results show that diabetes leads to changes in the fatty acid composition of the renal cortex and muscle, as well as of the liver and adipose tissue. At present it is not yet clear whether there is an absolute decrease in the proportion of essential fatty acids, or whether diabetes is characterized by an increase in the amount of lipids in both serum and tissues.     

Plasma netrin-1 is a diagnostic biomarker of human cancers

Context:?The axon guidance cues netrin-1 is a secreted protein overexpressed in many different cancer tissues.

Objectives:?To determine whether plasma netrin-1 can be used as a diagnostic biomarker of human cancer.

Materials and Methods:?A total of 300 cancer plasma samples from breast, renal, prostate, liver, meningioma, pituitary adenoma, glioblastoma, lung, pancreatic and colon cancer patients were compared against 138 control plasma samples. Netrin-1 levels were quantified by ELISA and immunohistochemistry.

Results:?Plasma netrin-1 levels were significantly increased in breast, renal, prostate, liver, meningioma, pituitary adenoma, and glioblastoma cancers as compared to control samples.

Discussion and Conclusion:?Our results suggest that plasma netrin-1 can be used as a diagnostic biomarker for many human cancers.     

On rat renal aminolevulinate transport and metabolism in experimental Fanconi syndrome

Hereditary tyrosinemia, an autosomal recessive disease of human infants, is characterized by severe liver disease, a renal Fanconi syndrome, and urinary excretion of large quantities of both aminolevulinate (ALA) and succinylacetone (SA). The latter is a metabolic end-product of tyrosine catabolism in affected individuals, produced by both liver and kidney, and is a potent inhibitor of aminolevulinate dehydratase (ALAD) in liver. This inhibition has been assumed to result in release of large amounts of aminolevulinate from liver into the circulation, with subsequent urinary excretion. In the present report we examine the effects of succinylacetone on rat renal cortical tubular handling of ALA and the relationship to tubular heme content, demonstrating a marked impairment of each. In contrast, maleic acid was found to have no effect on either renal ALAD or heme content. Thus, we conclude that renal handling of ALA in SA-treated rat renal cortex may indicate a contribution by the kidney to the increased net ALA excretion observed in hereditary tyrosinemia.     

Metal composition of human hepatic and renal metallothionein

This article is based on data on the levels of metals (Cd, Zn, Cu) and metallothionein (MT) determined radiochemically with²⁰³Hg in renal cortex and liver of 137 autopsy cases. From this number, for 23 cases, the gel filtration of the cytoplasmic fraction of the organs was performed. The molar content of metals in the MT fraction (Sephadex G-50) amounted to 46.9, 50.2, and 2.0% for Cd, Zn, and Cu in renal cortex, respectively, and to 8.3, 83.6, and 9.1% for Cd, Zn, and Cu in the liver, respectively. In parallel with the increase of Cd and MT in renal cortex, increasing saturation was found of the MT fraction by Cd, occurring at the expense of Zn and Cu. Equimolar amounts of Cd and Zn in the MT fraction are found at Cd level of 0.5 μmol Cd/g wet wt of renal cortex. In the liver, analogous dependency (elevation of %Zn, depression of %Cd and %Cu) were observed in relation to Zn and MT levels in this organ. The basic level of Zn (not bound with MT) was estimated at 0.5 μmol/g for both renal cortex and liver. A deficit of non-MT Zn in kidneys is proposed as an alternative mechanism of toxic Cd action.     

Molecular signaling mechanisms of renal gluconeogenesis in nondiabetic and diabetic conditions

The kidneys are as involved as the liver in gluconeogenesis which can significantly contribute to hyperglycemia in the diabetic condition. Substantial evidence has demonstrated the overexpression of rate-limiting gluconeogenic enzymes, especially phosphoenolpyruvate carboxykinase and glucose 6 phosphatase, and the accelerated glucose release both in the isolated proximal tubular cells and in the kidneys of diabetic animal models and diabetic patients. The aim of this review is to provide an insight into the mechanisms that accelerate renal gluconeogenesis in the diabetic conditions and the therapeutic approaches that could affect this process in the kidney. Increase in gluconeogenic substrates, reduced insulin concentration or insulin resistance, downregulation of insulin receptors and insulin signaling, oxidative stress, and inappropriate activation of the renin–angiotensin system are likely to participate in enhancing renal gluconeogenesis in the diabetic milieu. Several studies have suggested that controlling glucose metabolism at the renal level favors effective overall glycemic control in both type 1 and type 2 diabetes. Therefore, renal gluconeogenesis may be a promising target for effective glycemic control as a therapeutic strategy in diabetes.