Potential mechanism of cholagogic effect about Gardenia Jasminoides Ellis (Zhizi)-mediated increase of bile acids urinary excretion in normal rats / 中草药·英文版

Objectives: Gardenia Jasminoides Ellis (Zhizi), belonging to Rubiaceae family, has been traditionally used for treatment cholestasis and jaundice for centuries in Asian countries. In the theory of Traditional Chinese Medicines, Zhizi could dispel dampness and heat via the urine to execute its choleretic effects. However, the potential molecular mechanism has been still poorly clarified. Here, we investigated the effect of different dose of Zhizi aqueous extract powder (0.3 g/kg/d and 0.9 g/kg/d) on urinary excretion of bile acids (BAs), and defined the potential mechanism via renal BAs efflux transporters Mrp2 and Mrp4 in normal rats. Methods: Male Wistar rats were orally administrated with 0.3 or 0.9 g/kg/d dose of Zhizi aqueous extract powder for 2 weeks, then body weight, serum aminotransferase, total BAs concentrations in liver, bile, serum, kidney and urine, 1 h bile flow, 12-h urinary volume, biliary and urinary excretion amount of total BAs as well as protein expression of major renal BAs efflux transporter Mrp2 and Mrp4, were all evaluated. Results: Zhizi especially the high dose of Zhizi aqueous extract powder could reduce hepatic total BAs concentration. Additionally, bile flow and biliary excretion had no significant difference, but the remarkable increasing urinary excretion of BAs and 2 to 3 folds up-regulated renal Mrp2 expression were observed after administrated with Zhizi as compared with the control group. Conclusion: The findings indicate that Zhizi reduces hepatic total BAs level by increasing urinary excretion rather than the biliary excretion of BAs, which, in turn ascribed to elevated protein expression of Mrp2 at apical membrane of renal tubular epithelial cells.

Vital role of transporters in renal drug elimination / 药物评价研究

Transporters are a class of functional membrane proteins which are broadly expressed in the kidney and play a vital role in the reabsorption and secretion of many endogenous and xenobiotic compounds by the kidney.The renal proximal tubule is the primary site of transporter-mediated active transport for many drugs,including organic anion drugs,organic cation drugs and peptide drugs.Transporter-mediated drug-drug interactions may occur in the kidney when some drugs are co-administration.In this review,we focus on the location and function of major transporters in the kidney and summarize their vital role in renal drug elimination.

A Case of Isolated Glycosuria Mediated by an SLC5A2 Gene Mutation and Characterized by Postprandial Heavy Glycosuria Without Salt Wasting

Familial renal glycosuria (FRG) is an inherited disorder characterized by persistent glycosuria in the absence of hyperglycemia. It is caused by mutations in the sodium-glucose co-transporter, leading to increase in the renal excretion of glucose and sodium. However, there have been no studies on the role of fasting and postprandial changes in the urinary sodium excretion in patients with FRG. We report a case of renal glycosuria, which was confirmed by a SLC5A2 mutation via gene sequencing, and compared the postprandial urinary glucose and sodium excretion. A 26-year-old man sometimes experienced glycosuria on routine screening; however, other laboratory findings were normal. His fasting and postprandial urinary glucose excretion levels were 295mg/dL and 2,170mg/dL, respectively. The fasting and postprandial urinary sodium excretion levels were 200mEq/L and 89mEq/L, respectively. In patients with FRG, excessive diuresis might be prevented by a compensatory mechanism that reduces postprandial sodium excretion.

Steviol effect, a glycoside of Stevia rebaudiana, on glucose clearances in rats / O efeito do esteviol, um glicosídeo da Stevia rebaudiana, no clearance da glicose em ratos

Stevia rebaudiana, a South American plant normally used as a natural herbal sweetener, has been suggested as exerting beneficial effects on human health, including as an antihypertensive and antihyperglycemic. The present experiment was undertaken to evaluate the renal excretion of steviol, the aglycone of several natural products extracted from the leaves of S. rebaudiana, and to clarify the actual participation of this compound on the renal excretion of glucose in rats, which has been previously suggested as the preferential action of steviol on the Na+-glucose renal tubular transport system. Steviol was obtained by enzymatic hydrolysis of stevioside with pectinase. Thirty normal male Wistar rats weighing 345 g were used. After a control period, steviol was infused iv at three doses (0.5, 1.0 and 3.0 mg.kg-1/h), according to classical clearance techniques. During all the experiments no significant changes in inulin clearance (Cin) and p-aminohipuric acid clearance (C PAH) were observed. Administration of steviol resulted in a statistically significant increase in the fractional sodium excretion (FeNa+), fractional potassium excretion (FeK+), urinary flow as percent of glomerular filtration rate (V/GFR) and glucose clearance (C G) when compared to controls, but these effects were absent with the dose of 0.5 mg.kg-1/h. The steviol clearance (C S) was higher than the Cin and lower than the C PAH at all the doses employed in this study. The data suggest that steviol is secreted by renal tubular epithelium, causing diuresis, natriuresis, kaliuresis and a fall in renal tubular reabsorption of glucose.

Stevia rebaudiana, uma planta da América do Sul usada como adoçante natural, parece exercer efeitos benéficos para a saúde humana, incluindo ação anti-hipertensiva e anti-hiperglicêmica. No presente trabalho objetivamos avaliar a excreção renal do esteviol, uma aglicona extraída das folhas de S. rebaudiana, e elucidar a participação deste composto na excreção renal de glicose em ratos, o qual foi sugerido agir no sistema de transporte tubular renal Na+-glicose. O esteviol foi obtido por hidrólise enzimática com pectinase. Foram usados 30 ratos Wistar machos e pesando 345 g. Após um período controle, o esteviol foi infundido iv em três doses (0,5, 1,0 e 3,0 mg.kg-1/h) de acordo com técnicas clássicas de clearance. Durante os experimentos não houve alterações significantes no clearance da inulina (Cin) e do ácido-aminohipúrico (C PAH). A administração de esteviol resultou em um aumento estatisticamente significante na excreção fracional de sódio (FeNa+) e potássio (FeK+ ), no fluxo urinário como porcentagem da taxa de filtração glomerular (V/GFR) e do clearance de glicose (C G) quando comparados aos animais controles, embora estes efeitos estivessem ausentes na dose de 0,5 mg.kg-1/h. O clearance de esteviol (C S) foi maior que o Cin e menor que o C PAH em todas as doses usadas nos experimentos. Os dados sugerem a secreção de esteviol pelo epitélio tubular renal, causando diurese, natriurese, caliurese e uma redução na reabsorção tubular renal de excreção de glicose.

Comparison between Kidney and Hemoperfusion for Paraquat Elimination

The mortality rate of acute paraquat (PQ) poisoning depends on the PQ concentration in the blood. It has been shown that the kidneys eliminate PQ effectively. However, early renal function deterioration is frequently observed in acute PQ intoxication. This study is designed to compare the efficacy of PQ elimination with hemoperfusion (HP) and kidneys, taking into account the functional deterioration of the kidneys. The amount of renal and HP excretion of PQ were measured during the procedure of HP in patients with acute PQ intoxication. The PQ clearance and the actual amount of PQ elimination by the HP cartridge during the HP procedure were 111+/-11 mL/min (range; 13.2-162.2 mL/min) and 251.4+/-506.3 mg (range; 4.6- 1,655.7) each. While, the renal clearance and actual amount of renal elimination of PQ was 79.8+/-56.0 mL/min (range; 9.7-177.0) and 75.4+/-73.6 mg (range; 4.9- 245.8). As the creatinine clearance decreased, the PQ elimination by HP was as effective as or more effective than the renal elimination. In conclusion, early HP must be provided for life saving treatment in patients with acute PQ intoxication.

Renal Excretion and Distribution of Platinum of 3 Kinds of Platinum Preparation in Rats:A Comparative Study / 中国药房

OBJECTIVE:To study the mechanism of renal toxicity of platinums in rats.METHODS:A total of 12 rats were equally assigned to receive cisplatin,carboplatin,or dicycloplatin i.v with the dosage of platinum at 10 mg?kg-1.The cumulative excretion rate of platinum in urine in 4 h and the concentration of platinum in renal tissue were measured by atom absorption method.RESULTS:The total excretion percent of platinum in urine in the first 4 h after injection of cisplatin,carboplatin,and dicycloplatin were(33.7?5.7)%,(89.1?8.5)% and(70.1?9.8)% respectively.The renal platinum concentration were 70.6?31.6,217.7?97.6,and(278.8?112.0)?g?g-1,respectively.CONCLUSIONS:Both the renal excretion speed and renal concentrations of platinum were higher for dicycloplatin and carboplatin than for cisplatin.The nephrotoxicity of platinum drugs probably has no direct relationship with the renal concentration of platinum.

The Effect of Bilateral Renal Pedicle Ligatin on the Action of Mivacurium in Rabbits / 대한마취과학회지

Mivacurium, a new neuromuscular blocking agent, is known not to rely greatly on the renal function for its elimination, therefore, is recommended for the renal failure patient. In these studies, we investigated neuromuscular blocking action of mivacurium in case of bilateral ligation of renal pedicles to prevent the renal excretion and compared its action to that of pancuronium, which is mainly excreted by the kidney. Rabbits were divided into 4 groups: the mivacurium control group, the mivacurium group, the pancuronium control group, and the pancuronium group. Both renal arteries were ligated in the mivacurium group and the pancuronium group. After intravenous administration of mivacurium or pancuronium, the6neuromuscular blocking actions were observed. The results were as follows: 1.There was no significant difference in onset time between the mivacurium group(77+/-18.6 sec) and the mivacurium control group(100+/-36 sec). No significant difference between the pancuronium group(90+/-42 sec) and the pancuronium control group(101+/-43.8 sec), too. And no significant difference in change of onset time was found between the mivacurium group and the pancuronium group. 2.There was no significant difference in duration of action between the mivacurium group ,(664+/-85.2 sec) snd the mivacurium control group(500+/-134.4 sec). But significant difference was found between the pancuronium group(3453+/-1088.4 sec) and the pancuronium control group(1041+/-304.2 sec)(P<0.05). In the pancurounium group, the prolongation of duration of action was significantly greater than that in the mivacurium group(P<0.05). 3.There was no significant difference in recovery index between the mivacurium group (316+/-99.6 sec) and the mivacurium control group(230+/-66.3 seo). But there was significant difference between the pancuronium group(676+/-162.3 sec) and the pancuronium control group(274+/-92 sec)(P<0.05). The prolognation of recovery index in the pancuronium group was significantly greater than that in the mivacurium group(P<0.05).

Renal Excretion of Pancreatic Enzyme in Dogs / 대한비뇨기과학회지

It is generally accepted that in acute pancreatitis, the enzymes normally excreted by the pancreas are released from the disrupted parenchyma into the extraductal space and taken up by way of the lymphatics and capillaries. The enzymes in the blood stream may appear in high concentration in the serum. Therefore, serum amylase and lipase determinations has long been a mainstay in the diagnosis of acute pancreatitis and other pancreatic diseases. However, many investigators have claimed that the urinary output of amylase may be elevated more consistently in acute pancreatitis than in the serum concentration of either amylase or lipase, and urinary amylase measurement is a more sensitive reflection of the presence of pancreatitis and of its clinical course than is the measurement of serum amylase or lipase. Clinically, one of the ominous signs which may develop during the early course of acute pancreatitis is severe hypotension. But, no agreement has been reached among investigators as to the cause of the hypotension, although several investigators have implicated a blood volume deficiency resulting form inflammatory process, and hypercalcemia. Perhaps, the majority have attributed the hypotension to systemic effect of some of the pancreatic enzymes, especially trypsin. Nevertheless, the correction of these factors sometimes fail to restore a normal blood pressure clinically. The purpose of the present investigation was to observe the relationships between serum concentration and urinary output of pancreatic enzymes, and to determine the degree of hypotension resulting from the systemic administration of pancreatic enzymes. These experimental procedures, consisted of heteroinfusion of human pancreatic juice and homoinfusion of canine pancreatic emulsion intravenously, and pancreatic ductal ligation in dogs. Blood and urine samples for the enzyme analysis were collected serially thorough the femoral vein and ureteral catheter before and after the procedure. Blood pressure was measured consistently by the kymograph before and after infusion of pancreatic juice. Activities of amylase and lipase were determined by methods of Nelson and, Cherry and Crandall, respectively. The results obtained are summarized as follows; 1. Following intravenous infusions of pancreatic juice exogenously. serum and urine concentrations of amylase and lipase increased rapidly, but these enzymes decreased rapidly in urinary excretion and gradually in serum concentration. Urinary recovery of amylase was approximately 10% of the total infused amount of pancreatic juice at the end of 4 hours. 2. Following ligation of the pancreatic duct, the amylase and lipase levels of serum rose gradually and reached the maximum at 24-48 hours after ligation and then gradually fell. The output of these enzymes in the urine were relatively constant while serum enzymes were increased. 3. When the human pancreatic juice was infused, hypotension was pronounced, and it was deeper and more prolonged in hypotensive effect with infusion of highly concentrated juice in the enzyme activities. With human pancreatic juice, a more sustained hypotension occurred than was observed after infusion of canine pancreatic emulsion. As a result of this investigation, it is felt that the hypotension in acute pancreatitis is probably the result of pancreatic enzymes itself. 4. In postinfusion period, the urine volume was markedly decreased following hypotension, and the urine volume was increased following blood pressure to normal level. This suggests that urine volume may diminish resulting from transient acute renal failure due to hypotensive effect by pancreatic enzymes.