The Change of Glutathione Metabolism in Liver and Kidney of Cisplatin treated Rats

Cisplatin 투여 후 백서의 간 및 신장에서 Glutathione 대사의 변화

Glutathione (GSH) is a well-known antioxidative cellular component which is ubiquitous in nature. Several enzymes involved in GSH metabolism and recycling have been found to play important roles in detoxification of xenobiotics and free radicals. In this study, total GSH content, activity of GSH peroxidase and GSH reductase were measured in liver and kidney of cisplatin treated rats. Total GSH content (mM/g protein) of liver was higher in cisplatin treated rats ($1.51{\pm}0.28$) than of nontreated control ($0.95{\pm}0.28$), and in kidney, it was also higher in cisplatin treated rats ($0.87{\pm}0.20$) than that of control ($0.68{\pm}0.14$). The activity of GSH peroxidase (${\mu}M/mg$ protein/min) was lower in liver of cisplatin treated rats ($348.0{\pm}18.54$) than that of control ($415.5{\pm}53.15$), in kidney it was increase din cisplatin treated rats ($380.5{\pm}51.86$) compared to control ($327.3{\pm}20.36$). The activity of GSH reductase (${\mu}M/mg$ protein/min) was higher in liver of cisplatin treated rats ($3.09{\pm}0.88$) than that of control ($2.28{\pm}0.61$), in kidney it was also higher in cisplatin treated rats ($8.50{\pm}2.62$) than that of control ($3.30{\pm}1.10$). In summary, detoxification of ciplatin was revealed lesser effect in kidney as show increasion of GSH peroxidase and reductase and detoxification of cisplatin was expressed effectively in liver by increasing of GSH content and decreasing GSH peroxidase.

Cisplatin을 투여한 흰쥐의 간장 및 신장에서GSH의 역할을 관찰하고자 총 GSH의 농도, GSH peroxidase 및 GSH reductase이 효소활성도를 관찰하여 다음과 같은 결과를 얻었다. 총 GSH의 양(mM/g protein)은 간에서는 cisplatin을 투여한 군($1.51{\pm}0.28$)이 대조군(0.95+0.28)에 비해 현저히 증가하였으며 (p<0.01), 신장에서도 cisplatin 투여군(0$0.87{\pm}0.20$)이 대조군($0.60{\pm}0.14$)에 비해 유의하게 증가하였다(p<0.05). GSH peroxidase의 활성도(${\mu}M$ NADPH/mg protein/min)는 간장에서 cisplatin을 투여한 군($348.0{\pm}18.54$)이 대조군(415.5+53.15)에 비해 현저히 감소하였으며(p<0.01), 신장에서도 cisplatin 투여군($380.5{\pm}51.86$)이 대조군($327.2{\pm}20.36$)에 비해 유의하게 증가하였다(p<0.01). GSH reductase의 활성도(${\mu}M$ NADPH/mg protein/min)는 간장에서 cisplatin 투여군($3.09{\pm}0.88$)이 대조군(2.28+0.61)에 비해 현저히 증가하였으며(p<0.01), 신장에서도 cisplatin 투여군($3.30{\pm}1.01$)에 비해 cisplatin 투여군($8.50{\pm}2.62$)이 현저히 증가하였다(p<0.01). Cisplatin 투여로 인한 해독작용은 간에서는GSH의 양이 신장과 비교시 현저히 증가하였고 GSH reductase의 증가 및 GSH peroxidase의 감소로cisplatin해독에 GSH가 많이 이용되어 해독작용이 신장보다 더 잘 일어났으며 신장에서는 GSH가 증가하였으나 두 효소 모두 증가하였으므로 GSH가 일부 산화형으로 이용되어 간에서 보다는 해독작용이 적게 나타난 것으로 생각된다.