Possible Interaction: Antioxidants and Cyclosporine

“Co-treatment with antioxidants significantly abrogated cyclosporin A –induced endothelial cell activation.”

“This work identifies a previously undescribed mechanism underlying a significantly adverse …-target effect of cyclosporin A and suggests that co-treatment with antioxidants would inhibit the …-promoting effects of cyclosporin A. Implications: Targeting the proangiogenic effects of cyclosporin A may be useful in the management of transplant-associated cancers.”

“Supplementation with anti-oxidants Vitamin C and E decreases cyclosporine A trough-levels in renal transplant recipients.”

“So, the use of antioxidants seems to be a useful tool in attempting to reduce CsA adverse effects.”

“Although there are few data in humans treated with CsA, the possibility exists that antioxidants can also neutralize CsA nephrotoxicity and LDL oxidation.”

“ Antioxidant nutrients (e.g. Vitamins E and C) can neutralize some of the effects that CsA produced in the kidney.”

“ Antioxidants can also improve renal function and histological damage produced by CsA administration.”

“ Antioxidants have been shown to be protective in cyclosporine A nephrotoxicity.”

“Co-administration of CsA with the antioxidant N-acetylcysteine significantly decreased lipid peroxidation and also partially corrected the CsA-induced unfolded protein response.”

“Although more detailed pharmacokinetic analysis is necessary to clarify the exact mechanism of this interaction, physicians who take care of transplant recipients should be aware that more frequent CsA concentration monitoring is warranted after initiating these anti-oxidant agents.”

“ Antioxidant supplementation resulted in a significant decrease (…<0.05) in blood trough CsA by 24% (mean+/-SD, pre- 127.3+/-38.9, post- 97.2+/-30.7 microg/ml) compared with no change while taking the placebo (pre- 132.2+/-50.6, post- 138.6+/-56.0 microg/ml).”

“Furthermore, we observed that the inhibition of apoptosis by antioxidants correlated with an increased cell proliferation, suggesting that the immunomodulation of both DXM and CsA may be related to induction of apoptosis.”

“In con¬trast, therapeutic concentrations of CSA cause Bcl‐2 up‐regulation and modification of EC morphology, both effects blocked by antioxidants.”