Presenter: Aleena George 
Mentor: Carmen De Miguel, Ph.D.

ABSTRACT
The vasoactive peptide endothelin-1 (ET-1) is critical in lung and kidney injury. Renal damage and hyperoxia-induced lung disease are more prevalent in males than females. Aurothioglucose (ATG), inhibitor of thioredoxin reductase-1, attenuates hyperoxia-induced lung injury in mice; however, the effects of hyperoxia and/or ATG treatment on the kidney ET-1 system remain unknown. We hypothesized that hyperoxia would activate the renal ET-1 system and that ATG treatment would attenuate this activation. Male and female adult C57B/6 mice received a single injection of saline or ATG (25mg/Kg, i.p.) and were exposed to room air (RA) or >90% O2 for 72 hours. Kidney and spleen were collected for assessment of the ET-1 system by RT-PCR, glomerular morphology and immune cell infiltration. In males, hyperoxia reduced the cortical expression of ET-1 (RA vs. hyperoxia: 1 ± 0.05 vs. 0.34 ± 0.04, p<0.05; n=3-4/group) and ameliorated ETA expression. ATG treatment in RA significantly halved ET-1 and ETB expression, but had no effect in hyperoxia. Contrarily, hyperoxic females showed a 3-fold upregulation of cortical ETB expression that was prevented by ATG (saline vs. ATG: 2.80 ± 0.37 vs. 0.95 ± 0.27, p<0.05). ATG treatment in hyperoxic females decreased expression of ET-1 and ETA. No changes in cortical inflammation and glomerular morphology were observed. In hyperoxia, splenic ET-1 expression increased by 4-fold and 7-fold with ATG treatment. These results demonstrate sex differences in the effects of hyperoxia and ATG treatment in the renal ET-1 system and highlight it as possible therapeutic target to attenuate hyperoxia-induced kidney damage.