کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5853052 | 1130856 | 2011 | 7 صفحه PDF | دانلود رایگان |

To better understand species differences in cisplatin nephrotoxicity, we focused on renal cysteine-S-conjugate β-lyase (C-S lyase), which may play a crucial role in the metabolism of platinum (Pt)-cysteine conjugates. Aminooxyacetic acid hemihydrochloride (AOAA), an inhibitor of C-S lyase, reduced renal injuries due to cisplatin in rats, suggesting involvement of C-S lyase. On day 5 following a bolus cisplatin injection, three species showed in vivo nephrotoxic potentials in the order of rats > mice = rabbits (the highest to lowest), based on body surface. The levels of renal Pt residue at the nephrotoxic dose were in order of rabbits > rats > mice. Meanwhile, the activity of endogenous (basal) mitochondrial aspartate aminotransferase (AST), one of the C-S lyases, in the renal cortex of naive animals was rats > mice = rabbits. In a qualitative Western blot analysis, expression of mitochondrial C-S lyase in the kidney was observed at approximately 37 kDa in all five species used. In in vitro studies, the cytotoxicity of cisplatin was dependent on the expression level of C-S lyase mRNA in the respective renal cells. These results demonstrate that species differences in cisplatin nephrotoxicity are attributable to an interaction of renal Pt transition with C-S lyase activity.
⺠We studied on species differences in cisplatin nephrotoxicity using several animals. ⺠We confirmed the protective action of the C-S lyase inhibitor AOAA on cisplatin nephrotoxicity. ⺠The order of its nephrotoxic potentials was consistent with that of endogenous mitochondrial AST activities in the kidney. ⺠The cytotoxic potential of cisplatin was dependent on the expression level of C-S lyase mRNA in the in vitro system. ⺠Species differences in cisplatin nephrotoxicity were related to an interaction of renal Pt transition with C-S lyase activity.
Journal: Food and Chemical Toxicology - Volume 49, Issue 9, September 2011, Pages 2053-2059