Arachidonic acid metabolites mediate the radiation-induced increase in glomerular albumin permeability. Exp Biol Med (Maywood) 2006 Jan;231(1):99-106
Date
12/29/2005Pubmed ID
16380650DOI
10.1177/153537020623100112Scopus ID
2-s2.0-30344462388 (requires institutional sign-in at Scopus site) 22 CitationsAbstract
Radiation-induced renal injury is characterized by proteinuria, hypertension, and progressive decline in renal function. We have previously shown that in vivo or in vitro irradiation of glomeruli with a single dose of radiation (9.5 Gy) increases glomerular albumin permeability (P(alb)) within 1 hr. The current studies tested the hypothesis that this early radiation-induced increase in P(alb) is caused by the release of arachidonic acid and by the generation of specific arachidonic acid metabolites. Glomeruli obtained from WAG/Rij/MCW rats and cultured rat glomerular epithelial and mesangial cells were studied after irradiation (9.5 Gy, single dose). Arachidonic acid release and eicosanoid synthesis by glomeruli or cultured glomerular cells were measured after irradiation, and the effect of inhibitors of phospholipase A2 (PLA2) and cyclooxygenase (COX) on the irradiation-induced increase in P(alb) was assessed. Arachidonic acid release was demonstrated within 10 mins of irradiation of isolated glomeruli and monolayer cultures of glomerular epithelial and mesangial cells. Prostaglandin F(2alpha) (PGF(2alpha)) and PGE2 release was increased after irradiation of isolated glomeruli. Blocking arachidonic acid release or COX activity before irradiation completely prevented the increase in P(alb). COX inhibition immediately after irradiation also diminished the radiation-induced increase in P(alb). We conclude that arachidonic acid and its COX metabolites play an essential role in the early cellular changes that lead to the radiation-induced increase in P(alb). Understanding of the early epigenetic effects of irradiation may lead to new intervention strategies against radiation-induced injury of normal tissues.
Author List
Sharma M, McCarthy ET, Sharma R, Fish BL, Savin VJ, Cohen EP, Moulder JEMESH terms used to index this publication - Major topics in bold
AlbuminsAnimals
Arachidonic Acid
Cells, Cultured
Cyclooxygenase 2 Inhibitors
Dinoprostone
Eicosanoids
Epigenesis, Genetic
Epithelial Cells
Kidney Glomerulus
Mesangial Cells
Permeability
Phospholipases A
Phospholipases A2
Radiation Injuries, Experimental
Rats
Whole-Body Irradiation