The Lowering Effect of Probucol on Plasma Lipoprotein and Proteinuria in Puromycin Aminonucleoside-Induced Nephrotic Rats

Hirano, Tsutomu; Mamo, John; Nagano, Seishi; Sugisaki, Tetsuzo

doi:10.1159/000186385

Cited by 26 publications

(19 citation statements)

References 15 publications

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“…A third explanation for the failure to gain more weight during the high salt diet may be the significant proteinuria that occurred in recipients of an SHRSP kidney. In a recent study in rats, 35 puromycin aminonucleoside-induced proteinuria of 400-500 mg/day accounted for a deficit in body mass of approximately 50 g. Although in our study proteinuria was far less severe, it may still be partly responsible for the failure of sodium-retaining recipients of an SHRSP kidney to gain more body weight during a high salt diet than recipients of an F,H or WKY kidney.…”

Section: Resultscontrasting

confidence: 51%

Sodium retention and hypertension after kidney transplantation in rats.

Maser-Gluth

Keizer

et al. 1993

Hypertension

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The present study was designed to investigate the development of blood pressure and renal sodium handling in recipients of renal grafts from adult stroke-prone spontaneously hypertensive rats (SHRSP), normotensive Wistar-Kyoto (WKY) rats, and borderline hypertensive F, hybrids bred from SHRSP and WKY rats. Unilaterally nephrectomized F, hybrids served as renal graft recipients. The second native kidney was removed 7 days after transplantation. Starting on the day of transplantation, renal graft recipients were put on a standard diet for 7 days followed by a low salt diet (0.18% salt) for 10 days and a high salt diet (1.8% salt) for another 14 days. In recipients of a renal graft from SHRSP donors, systolic blood pressure rose progressively from 140±4 mm Hg before to 190±7 mm Hg 4 weeks after transplantation. In contrast, in recipients of a renal graft from WKY rat donors, blood pressure fell during the same time from 139 ±7 mm Hg to 120 ±4 mm Hg. Blood pressure did not change significantly in recipients of a renal graft from F, hybrid donors (132±4 versus 138±7 mm Hg). With transition from a low salt to high salt diet, all rats exhibited renal sodium retention. The accumulating amount of sodium retained by the renal graft was significantly higher in recipients of an SHRSP kidney than in recipients of a WKY rat kidney at all days on the high salt diet. It was also higher in recipients of an SHRSP kidney versus recipients of an F, hybrid kidney on days 8 through 14 on the high salt diet and in recipients of an F, hybrid kidney versus recipients of a WKY rat kidney on days 1 through 5 on the high salt diet. On the low salt diet, urinary aldosterone excretion was lower in recipients of an SHRSP kidney compared with recipients of a WKY rat kidney. On the high salt diet, it was similar in both groups. Urinary corticosterone excretion was similar in both groups on the low salt diet and increased significantly on the high salt diet in recipients of an SHRSP kidney but not in recipients of a WKY rat kidney. At the end of the protocol, glomerular filtration rate, renal plasma flow, plasma sodium concentration, and fractional sodium excretion were not significantly different among groups. These results confirm our previous finding that recipients of a renal graft from SHRSP donors developed posttransplantation hypertension, whereas blood pressure actually decreased in recipients of a renal graft from WKY rat donors. In addition, the data demonstrate that posttransplantation hypertension in recipients of an SHRSP kidney is associated with increased renal sodium retention. (Hypertension 1993;21:724-730)

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Section: Resultscontrasting

confidence: 51%

Sodium retention and hypertension after kidney transplantation in rats.

Maser-Gluth

Keizer

et al. 1993

Hypertension

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“…Although the hypocholesterolemic effect of probucol has been well characterized in various species of ex perimental animal, as well as in human patients, the antioxi dant properties of the drug have recently received increased attention. The antiatherogenic properties of probucol, espe cially those related to its antioxidant properties, have been demonstrated in vivo in the Watanabe heritable hyperlipidemic rabbit [31,40], as well as in cholesterol-fed rabbits [41], The favorable effects of probucol, related to its antioxi dant properties, on renal diseases have also been proposed in rats with bilateral ureteral obstruction [42], in rats with puromycin aminonucleoside-induced nephrosis [43], and in rats with subtotal kidney ablation [44], In most of these studies probucol was administered at 1% by weight in the diet. In a preliminary study, we also examined the effects of administration of probucol at 1% and 2% on renal injury in the ExHC rat (the number of rats examined was 5 in each case).…”

Section: Discussionmentioning

confidence: 99%

Probucol Reduces Renal Injury in the ExHC Rat

Hattori¹,

Ito²,

Kawaguchi³

et al. 1994

Nephron

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To investigate the potential roles of oxidized lipoproteins and glomerular macrophages in the pathogenesis of lipid-induced glomerular injury, we examined the effects of administration of probucol on the development of renal injury in ExHC rats. ExHC rats are derived from the Sprague-Dawley strain and are highly susceptible to dietary hypercholesterolemic stimuli. We reported previously that ExHC rats fed a cholesterol-supplemented diet (HCD) develop proteinuria and characteristic glomerular lesions. These lesions include marked accumulation of numerous lipid-filled foam cells, which have a surface marker that identifies them as macrophages, within mesangial regions, as well as segmental clusters of foam cells that are associated with capsular adhesions, the destruction of glomerular tufts and glomerular sclerosis. ExHC rats were maintained on an HCD or on an HCD supplemented with 5% (wt/wt) probucol for 8 weeks. Probucol reduced the extent of renal injury, as evidenced by proteinuria and segmental glomerular lesions, in ExHC rats fed an HCD, in the absence of any significant reduction in plasma cholesterol levels. Both low-density lipoprotein and β-very-low density lipoprotein isolated from the plasma of probucol-treated rats were found to be resistant to oxidative modification by cupric ions. Both the size and the number of foam cells within glomeruli in the probucol-treated rats were significantly reduced as compared to those of foam cells in the untreated rats. Probucol might reduce renal injury in ExHC rats by limiting the oxidative modification of lipoproteins and, subsequently, by restricting the foam cell transformation of macrophages within glomeruli and by inhibiting the recruitment of macrophages into glomeruli. The results of the present study may be interpreted to indicate that local glomerular oxidative modification of lipoproteins might occur in vivo, and both oxidized lipoproteins and glomerular macrophages may play important roles in the pathogenesis of lipid-induced glomerular injury.

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“…Probucol has been shown to decrease oxidation of LDL and VLDL in streptozotocin diabetic rats and in VLDL from nephrotic rats. 9 - 10 In this study we report the effects of probucol on the clearance from plasma and on organ uptake of triglyceride-rich lipoproteins in normal and diabetic rats.…”

Section: H Ypertriglyceridemia and Hypercholesterolemiamentioning

confidence: 98%

Effect of probucol on plasma clearance and organ uptake of chylomicrons and VLDLs in normal and diabetic rats.

Mamo

Elsegood

Umeda

et al. 1993

Arterioscler Thromb

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Probucol was given to rats made diabetic by streptozotodn. Compared with diabetic rats not receiving probucol or with nondiabetic rats, probucol lowered the plasma concentrations of trigrycerkies, phospholipids, cholesterol, and apolipoproteln B. The concentrations of serum chylomicrons and very low density lipoprotein (VLDL) were also reduced. In control and diabetic rats, probucol enhanced the clearance of endogenoushy radiolabeled VLDL from the plasma. Clearances from the plasma of rat lymph chylomicrons or chylomicronlike lipkJ emulsions were slow in diabetic rats. Probucol normalized chyiomicron clearance in diabetic rats primarily by restoring hepatic uptake of remnants, which was decreased in diabetes. In diabetic rats, uptake of chyiomicron remnants was increased in a number of extrahepatic tissues, including the heart and kidney. Probucol significantly decreased uptake in some extrahepatic tissues. Increased plasma clearance of VLDL and chylomicrons was associated with an increase in the apolipoprotein CH/Clll and apolipoprotein E/C ratios. Orally administered probucol was specifically incorporated into lymph chylomicrons, and clearance of probucol from the plasma exactly paralleled the clearance of chyiomicron remnants, as traced with radiolabeled cholesteiyl esters. Chylomicron-like emulsions incorporating probucol were exclusively cleared from the plasma by the liver in normal rats. We conclude that in streptozotodn diabetic rats, probucol is an effective hypolipidemic agent because it promotes the clearance of the trigiyceride-rich lipoproteins. are frequently found in patients with diabetes mellitus. The hyperlipidemia primarily reflects slow clearance of plasma lipoproteins, although overproduction of lipoproteins may also be a contributing factor in non-insulin-dependent diabetes.1 A defective clearance from the plasma of chylomicrons and very low density lipoproteins (VLDLs) has been reported in human diabetic patients (for a review, see Howard 1 ) and in animal models of this disease.2 " 4 Hydrolysis of triglycerides may be compromised by severe insulin deficiency because insulin maintains the synthesis and secretion of lipoprotein lipase in some tissues.5 Posthydrolysis clearance of the remnant particles is also delayed, 6 although the reasons for this are unclear. Elevated plasma concentrations of triglycerides and cholesterol are thought to contribute to the high incidence of atherosclerosis in diabetic patients, and so it is desirable to reduce the concentrations of these lipids. Probucol is a potent hypolipidemic agent that reduces serum cholesterol level principally by increasing the fractional catabolic rate of low density lipoprotein (LDL). 7 ? Probucol is an effective lipid antioxidant, but it is not clear whether its pharmacological actions on the metabolism of LDL are related to the prevention of oxidation. Lipoproteins from diabetic donors show increased amounts of oxidative products compared with lipoproteins of nondiabetic origin. Probucol has been shown to decrease oxidation of...

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The Lowering Effect of Probucol on Plasma Lipoprotein and Proteinuria in Puromycin Aminonucleoside-Induced Nephrotic Rats

Cited by 26 publications

References 15 publications

Sodium retention and hypertension after kidney transplantation in rats.

Sodium retention and hypertension after kidney transplantation in rats.

Probucol Reduces Renal Injury in the ExHC Rat

Effect of probucol on plasma clearance and organ uptake of chylomicrons and VLDLs in normal and diabetic rats.

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