Glomerular filtration rate and kidney blood flow in alloxan and streptozotocin diabetic rats

Foy, J. M.; Salih, A. K. M.

doi:10.1007/bf01949956

Cited by 6 publications

(2 citation statements)

References 16 publications

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“…Based on the CL R values of metformin based on plasma data (Table 3), reported renal blood flow rate of 54.8 (34) and 42.3 (40) mL/min/kg for the control and DMIA rats, respectively, and hematocrit and kidney weight (Table 1), the renal extraction ratios of metformin (CL R of metformin / renal plasma flow rate; only for urinary excretion of unchanged drug) were estimated. The renal blood flow rates were estimated to be 707 and 418 mL/min/100 g kidney weight for the controls and 7-day alloxan (50 mg/kg) diabetic male CFE rats, respectively (40). The renal extraction ratios of metformin thus estimated were 39.0 and 46.2% for the control and DMIA rats, respectively, suggesting that the metformin is an intermediate renal extraction drug for both groups of rats.…”

Section: Discussionmentioning

confidence: 90%

Effects of Diabetes Mellitus Induced by Alloxan on the Pharmacokinetics of Metformin in Rats: Restoration of Pharmacokinetic Parameters to the Control State by Insulin Treatment

Lee

Choi²,

Lee³

2008

J Pharm Pharm Sci

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PURPOSE. To test the effect of insulin treatment on the pharmacokinetics of metformin in rats with diabetes mellitus induced by alloxan (DMIA rats). The following results were reported from other studies. Metformin was metabolized via hepatic CYP2C11, 2D1, and 3A1/2 in rats. In DMIA rats, the protein expression and mRNA levels of hepatic CYP2C11 and 3A1/2 decreased and increased, respectively. In rat model of diabetes mellitus induced by streptozotocin, the protein expression of hepatic CYP2D1 was not changed. The increase in hepatic CYP1A2, 2B1, and 2E1, and decrease in hepatic CYP2C11 in DMIA rats was returned to the controls by insulin treatment. METHODS. Metformin (100 mg/kg) was administered intravenously and orally to the control rats, DMIA rats, and DMIA rats with insulin treatment for 3 weeks (DMIA rats with insulin). RESULTS. After intravenous administration of metformin to the DMIA rats, the CL R and CL NR of the drug were significantly slower than the controls. After oral administration of metformin to the DMIA rats, the AUC of the drug was also significantly greater than the controls. After intravenous administration of metformin to the DMIA rats with insulin, the significantly slower CL NR of the drug in the DMIA rats was returned to the controls. The altered pharmacokinetic indices observed following intravenous and oral administration of metformin to DMIA rats returned to the control values in the DMIA rats with insulin. CONCLUSIONS. The significantly slower CL NR of metformin in the DMIA rats could be due to the decrease in hepatic CYP2C11 than the controls. The comparable CL NR of metformin between the DMIA rats with insulin and the control rats could be due to restoration of hepatic CYP enzyme changes in DMIA rats to the controls.

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Section: Discussionmentioning

confidence: 90%

Effects of Diabetes Mellitus Induced by Alloxan on the Pharmacokinetics of Metformin in Rats: Restoration of Pharmacokinetic Parameters to the Control State by Insulin Treatment

Lee

Choi²,

Lee³

2008

J Pharm Pharm Sci

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“…Such an increase was already observed at 1 week after the STZ injection, but not in nonresponding rats. The K/B ratio may be a good indicator of experi mental diabetes, where hyperfunction of the kidneys occurs [4], In the studies on tissue fibrinolysis, sig nificant increases of direct nonplasmin fibri nolytic activity in the lung and spleen, and of plasminogen-activator activity in the lung were observed. The direct fibrinolytic activ ity was derived from a serine protease differ ent from plasmin [12].…”

Section: Discussionmentioning

confidence: 99%

Increase of Nonplasmin Fibrinolytic Activity in the Lung and Spleen of Streptozotocin-Induced Diabetic Rats

Okamoto

Nagamatsu

Yamamoto

et al. 1987

Pathophysiol Haemos Thromb

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In streptozotocin-induced diabetes in rats, nonplasmin fibrinolytic activity was found to be significantly increased in the lung and spleen, but not in the liver and kidney. The plasminogen-activator activities, either soluble or insoluble, were almost simultaneously increased in the lung, suggesting the possible release of plasminogen-activator from the lung to the blood. It seems likely that plasminogen-activator of the usual type and nonplasmin protease are also involved in thrombotic disorders in the experimental diabetes.

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Zur Morphologie und Pathogenese der diabetischen Glomerulosklerose

Romen

1980

Klin Wochenschr

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The diabetic glomerulosclerosis as a consequence of the abnormal metabolic state is characterized by an uniform thickening of the glomerular basement membrane (GBM) and an augmentation of the mesangial matrix. Both alterations begin already few years after the onset of the diabetes and are observed in all glomeruli to the same extent (=diffuse type). Later on, nodular deposits of glycoproteins are additionally found in the mesangium (=nodular type). Only these nodules are morphologically specific for the diabetic disorder. In association with both the diffuse and the nodular glomerulosclerosis, insudation of plasma can be seen in the afferent and efferent vessels and the glomerular capillary loops. The mechanism of the increase in the amount of GBM-material is not known, since contradictory data have been reported with regards to both the chemical composition and metabolism of the GBM in human and experimental diabetes. Some postulate that the abnormal deposition of GBM-mateiral is due to an excessive synthesis (anabolic disorder), others argue that a further decrease in the normally slow breakdown and disposal (catabolic disorder) might be responsible. This review presents the different pathogenetic concepts of the glomerulosclerosis and attemps to explain the possible causes for the current discrepancies.

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Glomerular filtration rate and kidney blood flow in alloxan and streptozotocin diabetic rats

Abstract: Glomerular filtration rate (GFR), cardiac output, regional blood flow and kidney weight were measured in alloxan and streptozotocin diabetic rats at different times after the administration of diabetogen. A high GFR was found together with increased kidney weight and reduced blood flow.

Cited by 6 publications

References 16 publications

Effects of Diabetes Mellitus Induced by Alloxan on the Pharmacokinetics of Metformin in Rats: Restoration of Pharmacokinetic Parameters to the Control State by Insulin Treatment

Effects of Diabetes Mellitus Induced by Alloxan on the Pharmacokinetics of Metformin in Rats: Restoration of Pharmacokinetic Parameters to the Control State by Insulin Treatment

Increase of Nonplasmin Fibrinolytic Activity in the Lung and Spleen of Streptozotocin-Induced Diabetic Rats

Zur Morphologie und Pathogenese der diabetischen Glomerulosklerose

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