TY - JOUR
T1 - Lipid peroxidation accompanies cyclosporine nephrotoxicity
T2 - Effects of vitamin E
AU - Wang, Chunyou
AU - Salahudeen, Abdulla K.
AU - Mcclain, Matthew
AU - Whitehead, Jacqueline
N1 - Funding Information:
This work was supported by a Baxter extramural grant to AKS. We
PY - 1995/3
Y1 - 1995/3
N2 - Cyclosporine A (CsA) has been demonstrated to induce renal microsomal lipid peroxidation in vitro. To examine whether CsA induces lipid peroxidation in vivo, uninephrectomized rats were gavaged with vehicle, CsA 12.5 or 25 mg/kg/day for four weeks. CsA-induced reduction in GFR and RBF was associated with a dose-related increase in renal cortical malondialdehyde (MDA) and conjugated diene, as well as a similar increase in arterial MDA. The latter was apparent within two hours of a single intraperitoneal injection of 25 mg/kg CsA and preceded the acute fall in GFR. To address whether lipid peroxidation contributed to CsA nephrotoxicity, rats were gavaged with vehicles, CsA 25 mg/kg/day or CsA plus vitamin E 25 mg/kg/day for eight weeks. Vitamin E, a lipid radical scavenger, inhibited MDA rise and reduced CsA-induced renal damage. Conversely, CsA administration to vitamin E and selenium deficient rats was accompanied by a greater increase in arterial MDA and fall in GFR. These novel findings, that CsA nephrotoxicity is associated with lipid peroxidation and that a chain-breaking antioxidant ameliorates whereas its deficiency exacerbates, indicate a role for lipid peroxidation, presumably free radical-mediated, in CsA toxicity.
AB - Cyclosporine A (CsA) has been demonstrated to induce renal microsomal lipid peroxidation in vitro. To examine whether CsA induces lipid peroxidation in vivo, uninephrectomized rats were gavaged with vehicle, CsA 12.5 or 25 mg/kg/day for four weeks. CsA-induced reduction in GFR and RBF was associated with a dose-related increase in renal cortical malondialdehyde (MDA) and conjugated diene, as well as a similar increase in arterial MDA. The latter was apparent within two hours of a single intraperitoneal injection of 25 mg/kg CsA and preceded the acute fall in GFR. To address whether lipid peroxidation contributed to CsA nephrotoxicity, rats were gavaged with vehicles, CsA 25 mg/kg/day or CsA plus vitamin E 25 mg/kg/day for eight weeks. Vitamin E, a lipid radical scavenger, inhibited MDA rise and reduced CsA-induced renal damage. Conversely, CsA administration to vitamin E and selenium deficient rats was accompanied by a greater increase in arterial MDA and fall in GFR. These novel findings, that CsA nephrotoxicity is associated with lipid peroxidation and that a chain-breaking antioxidant ameliorates whereas its deficiency exacerbates, indicate a role for lipid peroxidation, presumably free radical-mediated, in CsA toxicity.
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U2 - 10.1038/ki.1995.138
DO - 10.1038/ki.1995.138
M3 - Article
C2 - 7752594
AN - SCOPUS:0028913181
SN - 0085-2538
VL - 47
SP - 927
EP - 934
JO - Kidney International
JF - Kidney International
IS - 3
ER -