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논문분류	춘계학술대회 초록집
제목	PARP activation during cisplatin nephrotoxicity in zebrafish and mice
저자	Jinu Kim, Myoung-Jin Kim, Jehee Lee
출판정보	2019; 2019(1):
키워드	Zebrafish \| screening \| PARP \| cisplatin \| nephrotoxicity
초록	Cisplatin treatment in cancer therapy has a major side effect in that it causes nephrotoxic acute kidney injury, leading to a high mortality. Here, we developed a novel model to induce cisplatin nephrotoxicity in adult zebrafish of AB wild-type. We measured cisplatin-induced proximal tubular dysfunction using fluorescein-labeled dextran uptake and alkaline phosphatase stain in zebrafish. We also measured histological injury of kidney tubules using tubular injury score of periodic acid-Schiff-stained kidney sections in zebrafish. We demonstrated that intraperitoneal administration of cisplatin caused a decline of kidney proximal tubular function. We also showed that cisplatin-induced a histological injury of kidney tubules. As shown in a C57BL/6 mouse model of cisplatin nephrotoxicity, the activation of poly (ADP-ribose) polymerase (PARP), an enzyme implicated in cisplatin-induced cell death, was markedly increased after injecting cisplatin to zebrafish. Furthermore, pharmacological inhibition of PARP using specific PARP inhibitor PJ34 or 3-aminobenzamide ameliorated kidney proximal tubular function and histological structure in cisplatin-injected adult zebrafish kidneys, showing an additive effect after combination treatment with both inhibitors. This combination effect was also confirmed in the mouse model of cisplatin nephrotoxicity. These data suggest that adult zebrafish is not only suitable for drug screening, but also useful as a model to study the pathophysiology of cisplatin nephrotoxicity. (NRF-2016R1C1B2012080)
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