Lipoprotein oxidation and cytotoxicity: Effect of probucol on streptozotocin-treated rats

Chisolm, Guy M.; Morel, Diane W.

doi:10.1016/s0002-9149(88)80046-8

Cited by 50 publications

(21 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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: 97%

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

View full text Add to dashboard Cite

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...

show abstract

Section: H Ypertriglyceridemia and Hypercholesterolemiamentioning

confidence: 97%

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

View full text Add to dashboard Cite

show abstract

“…In particular, lipid peroxide is considered to be a factor in the progression of diabetic nephropathy 15) . Probucol was developed as a cholesterol-lowering agent and was found to have antioxidant effects [16][17][18] . Probucol has been reported to reduce lipid peroxide 19) ; urinary 8-hydroxy-2'-deoxyguanosine, which is an oxidative stress marker 20) ; and radical oxygen species in the glomeruli of diabetic rats 21) .…”

Section: Blood and Urine Samplingmentioning

confidence: 99%

“…We reported that probucol reduced urinary 8-hydroxy-2'-deoxyguanosine, a known marker of oxidative stress, in diabetic patients 20) . Other investigators have also reported that probucol possessed antioxidant as well as cholesterol-lowering effects [16][17][18][19] . Ban et al 29) demonstrated that probucol suppressed the expression of NADPH oxidase and reactive oxygen species in mesangial cells modulated by 7-ketocholesterol and high glucose.…”

Section: Renal Dysfunction and Other Eventsmentioning

confidence: 99%

Probucol Suppresses Initiation of Chronic Hemodialysis Therapy and Renal Dysfunction-Related Death in Diabetic Nephropathy Patients: Sakura Study

Endo

Saiki

Yamaguchi

et al. 2013

JAT

View full text Add to dashboard Cite

Aim: Probucol has antioxidant as well as cholesterol-lowering effects. We examined the effect of probucol on the progression of diabetic nephropathy. We named this study 'Sakura Study' after our hospital and city. Methods: We performed a randomized, open trial on 162 type 2 diabetic patients with clinical albuminuria (urinary albumin excretion ＞300 mg/g creatinine). Eighty patients were assigned to probucol treatment (500 mg/day) and 82 patients to no probucol treatment. All patients were followed for five years. The primary outcome was the time to renal dysfunction events, defined as the initiation of chronic hemodialysis therapy and renal dysfunction-related death. Results: Probucol decreased total cholesterol, HDL-cholesterol, and LDL-cholesterol compared to the control group. The serum creatinine increase rate was significantly lower (p = 0.015) in the probucol group (0.066 mg/dL/month) than in the non-probucol group (0.116 mg/dL/month). Renal dysfunction events occurred in 72 patients during this study. The 69 patients who were initiated on chronic hemodialysis comprised 42 in the non-probucol group and 27 in the probucol group. Three patients in the non-probucol group, but no patients in the probucol group died of renal dysfunction. The renal dysfunction event-free survival rate was significantly higher (log-rank: p = 0.02) in the probucol group than in the non-probucol group. Conclusion: Probucol suppressed the progression of diabetic nephropathy and renal dysfunction events.

show abstract

“…There is an increasing body ofevidence that oxidative modification of LDL may play a significant role in atherogenesis (4)(5)(6)(7)(8)(9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Minimally modified low density lipoprotein is biologically active in vivo in mice.

Liao¹,

Berliner²,

Mehrabian³

et al. 1991

J. Clin. Invest.

202

100

View full text Add to dashboard Cite

show abstract

Lipoprotein oxidation and cytotoxicity: Effect of probucol on streptozotocin-treated rats

Cited by 50 publications

References 19 publications

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

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

Probucol Suppresses Initiation of Chronic Hemodialysis Therapy and Renal Dysfunction-Related Death in Diabetic Nephropathy Patients: Sakura Study

Minimally modified low density lipoprotein is biologically active in vivo in mice.

Contact Info

Product

Resources

About