Increased lipid peroxidation in cyclosporin-treated heart transplant recipients

Chancerelle, Yves; Lorgeril, Michel de; Viret, Roseline; Chiron, B; Dureau, G; Renaud, S.; Kergonou, Jean-François

doi:10.1016/0002-9149(91)90665-8

Cited by 47 publications

(13 citation statements)

References 11 publications

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“…Other results [31] showed that an iron chelator had a pro tective effect in CsA-induced acute nephro toxicity. Recent work of Chancerelle et al [32] provides clinical evidence of chronic in vivo increased lipid peroxidation in cyclospo rin-treated heart transplant recipients, a con dition associated with accelerated coronary atherosclerosis. On the other hand, alteration in calcium homeostasis may influence the for mation of oxygen free radicals and subse quent lipid peroxidation.…”

Section: Possible Role O F Free Radicalsmentioning

confidence: 99%

Effects of Cyclosporin and Cremophor on Working Rat Heart and Incidence of Myocardial Lipid Peroxidation

Tatou

Mossiat²,

Maupoil³

et al. 1996

Pharmacology

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Cyclosporin A (CsA) is widely used as the immunosuppressant of choice for preventing graft rejection. However, its clinical use is hampered by certain side effects, especially its nephrotoxicity and other cardiovascular side effects. CsA for intravenous infusion contains cremophor (Cre) and this vehicle has significant adverse effects on endothelial function and vascular muscle. The present study was aimed at investigating the direct effects of CsA and Cre on isolated and perfused rat hearts in the dosage that closely approximates the peak level achieved for the prevention of graft rejection in the rat. Transplantation is a clinical setting in which the myocardium may be exposed to transient ischemia. In this study, we have shown that the vehicle of CsA, namely Cre, has significant adverse effects on cardiac function. We observed a reduction in coronary flow and aortic output. Addition of CsA appeared to induce a further reduction of aortic flow. We have also shown that a significant increase of thiobarbituric acid reactive substances, considered as an index of lipid peroxidation, occurred in the reperfused heart in the presence of Cre + CsA. Our experimental study shows that Cre turned out to be toxic to myocardium by itself. In the heart, potential Cre-CsA interactions possibly potentiating CsA toxicity could not be excluded. The increase of lipid peroxidation in the heart perfused with CsA suggests that reactive oxygen species may be involved in the detrimental effects of this substance on the heart.

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Section: Possible Role O F Free Radicalsmentioning

confidence: 99%

Effects of Cyclosporin and Cremophor on Working Rat Heart and Incidence of Myocardial Lipid Peroxidation

Tatou

Mossiat²,

Maupoil³

et al. 1996

Pharmacology

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“…In addition, recent evidence has shown that low density lipoproteins (LDL) isolated from renal transplant recipients treated with CsA showed an increased tendency to oxidize in vitro faster than LDL free of CsA [3,11,26,271. On the other hand, Chancellere, et a1 [6] showed that CsA-treated heart transplant recipients had increased levels of oxidized lipids circulating in their blood, suggesting that CsA promoted in vivo oxidation of circulating lipids. Oxidized lipids and oxidized LDL in particular, have several properties which are potentially atherogenic [25].…”

Section: Introductionmentioning

confidence: 99%

“…Hyperlipidemia or dislipidemia, which appears to be one of the strongest non-immunologic risk factors for posttransplant CAD, is common after kidney transplantation, and evidence indicates that immunosuppressive agents like cyclosporine (CsA), [6,8,15,16,21,23,291 and corticosteroids [13] play a role in posttransplant atherosclerosis. In addition, recent evidence has shown that low density lipoproteins (LDL) isolated from renal transplant recipients treated with CsA showed an increased tendency to oxidize in vitro faster than LDL free of CsA [3,11,26,271.…”

Section: Introductionmentioning

confidence: 99%

Tacrolimus, cyclosporine and plasma lipoproteins in renal transplant recipients

et al. 2001

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To compare the effect of tacrolimus (FK506) and cyclosporine (CsA) on plasma lipoproteins in renal transplant recipients receiving maintainance therapy, the following prospective study was undertaken. Blood from nineteen recipients on tacrolimus (FK group) and from twenty-one on CsA (CsA group) was collected at baseline, 3-, 6-, and 10-month intervals. Plasma lipids, lipoproteins and oxidation properties of lipoproteins were determined. Plasma total cholesterol, low density lipoprotein (LDL) cholesterol, and apolipoprotein B (apoB) were substantially increased in both groups, although only the CsA group showed significant differences at all time intervals and at the baseline. High density lipoprotein cholesterol, triglycerides, and apolipoprotein A varied in both groups at time intervals from the baseline, but not significantly. The susceptibility to oxidation of LDL isolated from the FK group at all times was uninfluenced by the tacrolimus treatment, and values were comparable to those obtained from LDL isolated from healthy individuals. A significantly higher susceptibility to oxidation as indicated by the shorter time required to start the formation of conjugated dienes was observed in LDL isolated from the CsA group at 3 and at 6 months of therapy. Tacrolimus-treated patients appear to have less hyperlipidemic and have LDL less susceptible to oxidation than patients treated with CsA.

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“…Therefore, we assume that the increase in lipid peroxide level is probably involved in the development of graft coronary disease. In this regard, Chancerelle et al [24] reported that the level of Schiff bases in the serum was elevated in cyclosporin-treated heart-transplant recipients and suggested that the increased lipid peroxidation was associated with graft coronary disease, though direct evidence for increased lipid peroxide level was not provided. Coles et al [25] reported that the level of myocardial conjugated dienes was increased during the intermediate stage of rejection in weanling piglets.…”

Section: Discussionmentioning

confidence: 99%

Increase in Serum Lipid Peroxide Level and Development of Intimal Proliferation in Graft Coronary Artery after Heart Transplantation in Rats.

Hashimoto

Fuwa

Komura

et al. 1993

J. Clin. Biochem. Nutr.

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SummaryChange in serum lipid peroxide level was examined in rats undergoing acute or chronic rejection of heart transplants, in order to clarify the role of lipid peroxides in the development of graft coronary disease. In the rat heart transplantation model under acute rejection conditions, the serum lipid peroxide level of the recipients did not change. While, in the chronic rejection model the level of the recipients significantly increased on the 15th day after the transplantation as compared with that of sham-operated control rats. Light microscopic observations of an allograft on the 15th day after the operation revealed the presence of inflammatory lesions involving infiltration of lymphocytes into the myocardium, edema, and necrosis. On the 22nd day after the operation, intimal thickening in the coronary artery was observed, and it became more remarkable on the 50th day. These results suggest that the increase in serum lipid peroxide level could be one of the signs of graft coronary disease.

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Increased lipid peroxidation in cyclosporin-treated heart transplant recipients

Cited by 47 publications

References 11 publications

Effects of Cyclosporin and Cremophor on Working Rat Heart and Incidence of Myocardial Lipid Peroxidation

Effects of Cyclosporin and Cremophor on Working Rat Heart and Incidence of Myocardial Lipid Peroxidation

Tacrolimus, cyclosporine and plasma lipoproteins in renal transplant recipients

Increase in Serum Lipid Peroxide Level and Development of Intimal Proliferation in Graft Coronary Artery after Heart Transplantation in Rats.

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