In this study, we investigated the kidney protective effects of eipoxyeicosatrienoic acid analog (EET-A) in experimental radiation nephropathy caused by total body irradiation (TBI) of 11 Gray (Gy). Male WAG/RijCmcr rats were divided into four groups: normal rats (control), TBI rats treated with vehicle (TBI-V), TBI rats treated with EET-A (10 mg/kg/d, TBI-EET-A) or captopril (30 mg/kg/d, TBI-Cap) in drinking water. Urine and plasma samples were collected after 12-week treatment to assess kidney protective effects of EET-A and captopril by determining blood urea nitrogen (BUN), proteinuria, albuminuria, nephrinuria, and histopathological examination. 12-week post TBI blood samples demonstrate elevated BUN level in TBI-V compared to control group (44±5 vs. 18±1 mg/dL, P&lt;0.001). EET-A and captopril treatments reduced BUN levels compared to TBI-V group (EET-A: 27±3 mg/dL and TBI-Cap: 18±1 mg/dL, P&lt;0.01). The TBI-V group had elevated urinary albumin (310±50 mg/d) compared to control (0.9±0.1 mg/d), and both EET-A and captopril treatments reduced it (P&lt;0.001). Moreover, TBI-V group demonstrate elevated urinary nephrin level (5.7±0.9 mg/d) compared to control (0.07±0.01 mg/d), and EET-A as well as captopril treatments attenuated this (P&lt;0.001). In brief, we demonstrate that the captopril and EET-A treatments mitigate kidney injury in radiation nephropathy, and EET analog could be a new therapeutic target to treat radiation nephropathy.

Epoxyeicosatrienoic acid analog mitigates kidney injury in experimental radiation nephropathy

249th National Meeting (2015)

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