Inhibition of lipid peroxidation down regulates inflammatory cytokines and inducible nitric oxide synthase (iNOS) in cold-preserved syngenic transplanted rat kidneys along with functional protection

Other Article (Journal Article)

Transplanted organs, which invariably undergo ischemia-reperfusion injury, upregulate the expression of inflammatory cytokines and iNOS. Such upregulations are causally linked to rejection episodes. Since lipid peroxidation contributes to ischemia-reperfusion-induced organ injury, we investigated the effect of inhibiting lipid peroxidation on the expression of cytokines and iNOS in the kidneys transplanted between Wistar-Furth rats. AS group received kidneys from donors injected intravenously with AS (10 mg/kg) just prior to harvest. AS was administered also to the recipient 30′ prior to reperfusion of the transplanted kidney. Kidneys were kept cold-preserved in UW solution for 24 hr prior to transplantation. Plasma malondialdehyde (MDA) was measured 15′ after reperfusion. The contralateral kidney and the graft were removed 4 and 6 days respectively. Control group underwent same procedure except vehicle was administered. AS group had better renal function and reduced lipid peroxidation (* p<0.05 vs. control): n=6 Plasma MDA (nmol/ml) Serum Creatinine (mg/dl) Control (UW) 10.7±0.6 2.8±0.2 AS (UW+AS) 6.8±0.6* 1.9±0.2* The control kidneys, transplanted without antioxidant coverage, demonstrated strong expression of iNOS mRNA (RT-PCR, n=2), which was completely inhibited by AS therapy. Cytokine expression was marked in the transplanted kidney for IL2 and IL6 (RT-PCR, n=2), and reduced with AS therapy. Transplantation-induced expression of TNF ∝ was, however, unaffected by AS. Taken together, the novel but preliminary findings herein support the view that oxidative injury, particularly lipid peroxidation, may stimulate the activation of cytokines-NO cascades, and their inhibition with antioxidants may limit further injury well as reduce the potential for triggering transplant rejection.

Duke Authors

Cited Authors

  • Wang, C; Hale, E; Lagoo-Deenadayalan, S; Barber, H; Salahudeen, A

Published Date

  • January 1, 1996

Published In

Volume / Issue

  • 44 / 1

International Standard Serial Number (ISSN)

  • 1708-8267

Citation Source

  • Scopus