Novel epoxyeicosatrienoic acid analog ameliorates renal injury in a rat model of radiation nephropathy (690.7)

Abstract

Arachidonic acid metabolites epoxyeicosatrienoic acids (EETs) protect the kidney in different pathologies. This study investigated the ability of a novel EET analog, EET‐A to mitigate experimental radiation nephropathy caused by total body irradiation (TBI, 11 Gy). Four groups of rats, normal male WAG/RijCmcr rats, TBI rats treated with vehicle (TBI‐V), EET‐A (10mg/kg/d p.o.) treated TBI rats (TBI‐EET‐A), and Captopril (30mg/kg/d p.o.) treated TBI rats (TBI‐Cap) were studied. Kidney damage was assessed from blood urea nitrogen (BUN), albuminuria, nephrinuria, and histopathological changes 12 weeks post TBI. The TBI‐V group had a 3‐fold increase in BUN level compared to control (158±14 vs 50±3 mg/dL). BUN level was lower in TBI‐EET‐A (85±6 mg/dL) and TBI‐Cap (52±2 mg/dL) compared to TBI‐V group. Albumin/creatinine ratio increased 94‐fold in TBI‐V group compared to control (6451±800 vs 20±5 μg/mg), and was reduced in TBI‐EET‐A (1652±382 μg/mg) and TBI‐Cap (103±28 μg/mg) groups. Nephrinuria increased 30‐fold in the TBI‐V compared to control group (15390±1897 vs 48±9 μg/d), and EET‐A (7071±2122) and captopril (222±107) decreased it. Moreover, renal tubular and glomerular injury was reduced in TBI‐EET‐A and TBI‐Cap groups compared to TBI‐V group. These data demonstrate that a novel EET‐analog, EET‐A reduces kidney injury in experimental radiation nephropathy caused by TBI.