[Effects of reactive oxygen species scavenger and platelet activating factor receptor antagonist on accelerated...

To elucidate the role of reactive oxygen species (ROS) in accelerated nephrotoxic nephritis (NTN), effects of SOD-mimic (Fe-TPAA) and anti-PAF (WEB-2086) on NTN were investigated. Three days after the preimmunization with normal rabbit IgG, anti-GBM rabbit IgG were administered unilaterally to the left kidney in order to examine the effect of circulating inflammatory factors by comparing with the contralateral kidney. Normal rabbit IgG were likewise injected to the control rats. Luminol amplified chemiluminescence (CL) assay of isolated glomeruli, histological examination and monoclonal antibody (anti LC-A Ab, anti PMN Ab, anti M phi Ab) positive-cell counting were performed in both kidneys. After induction of NTN, 3.4 mg/kg/day of Fe-TPAA and 2mg/kg/day of WEB-2086 were respectively administered by continuous injection using Osmotic pump. At day 7, glomerular CL and glomerular cellularity were both increased significantly in anti-GBM perfused kidney. Anti-rabbit IgG were also stained in the contralateral kidney, but clearly in lesser amount as compared with the anti-GBM perfused kidney, suggesting very slight glomerulonephritis may have occurred also in nonperfused kidney. While WEB-administration suppressed glomerular hypercellularity, CL and urinary protein, Fe-TPAA administration did only glomerular CL. Taking into account that dosing amount of Fe-TPAA was limited due to its toxicity, the effective ROS scavenging may not have been obtained. However, another possibility is proposed that WEB-2086 suppressed the development of glomerular lesion by not only inhibiting generation of ROS but also by release of other inflammatory factors.