Kidney Research and Clinical Practice

Korean Society of Nephrology (대한신장학회)
권호 표지

Effects of Supplementation with a Schizandrin C Derivative DDB-mixed Preparation (DWP-04) on Antioxidant Activity in Cisplatin-induced Nephrotoxicity in Rats

Schizandrin C 유도체 DDB 혼합물 DWP-04가 Cisplatin의 신독성 경감기전에 미치는 영향

Choi, Jong-Won;Kang, Hye-Ok;Jung, Yeon-Soon;Rim, Hark;Hur, Bang
최종원;강혜옥;정연순;임학;허방

  • Published : 20100000
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Abstract

Purpose : This study investigated the effect of reducing cisplatin induced nephrotoxicity with DWP-04 that is the compound of Schizandrin C derivative biphenyldimethyl dicarboxylate (DDB), glutathione and selenium. For the purpose of observation is that how DWP-04 has influence on mechanism of reducing cisplatin induced nephrotoxicity with renal function test, free radical formation and detoxification enzyme system in renal tissue. Methods : Five groups of rats were dosed with vehicle, cisplatin (2 mg/kg i.p.), cisplatin+DWP-04 (100, 200 mg/kg po), or cisplatin+sodium thiosulfate (200 mg/kg i.p.) daily for 4 weeks. Results : Serum creatinine, lactate dehydrogenase and activity of hydroxy radical increased in the cisplatin group and suppressed in the cisplatin+DWP-04 group compared to the cisplatin group. The renal tissue concentration of lipid peroxidase and lipofuscin were increased in the cisplatin group compared to the other groups. The activity of aminopyrine N-demethylase, aniline hydroxylase, aldehyde oxidase and xanthine oxidase, of which free radical formation system in kidney was also decreased in the cisplatin+DWP-04 group compared to the cisplatin and cisplatin+sodium thiosulfate group. The activity of detoxification system of free radical, such as glutathione S-transferase, superoxide dismutase, catalase and glutathione peroxidase were markedly increased in the cisplatin+DWP-04 group than the cisplatin and the cisplatin+sodium thiosulfate group (p<0.05). Conclusion : It can be concluded that the mechanism of decreasing cisplatin-induced nephrotoxicity by DWP-04 is that the decreasing of the amount of lipid peroxide and lipofuscin in the renal tissue by increasing activity of the antioxidant defense system and the decreasing of reactive oxygen species by increasing detoxification enzyme activity.

목 적 : Cisplatin 신독성 모델에서 오미자에서 추출된 Sch-zandrin C의 합성물질인 DDB, gluglutathion과 selenium의 복합물질인 DWP-04을 투여하여 신독성 경감효과를 알아보았다. 이 과정에서 신 조직 중 과산화지질 및 활성산소에 관여하는 효소계에 미치는 효과를 조직학적 검사와 병행하여 비교 검토하였다. 방 법 : 백서는 정상 대조군 (n=5), Cisplatin 단독 투여 대조군 (n=10), DWP-04 100 mg/kg 투여군 (n=10), DWP-04 100 mg/kg 투여군 (n=10)과 sodium sulfate 200 mg/kg 투여군 (n=10)으로 나누어 4주간 약물치료 한 후 검체를 얻었다. 결 과 : 혈청 크레아티닌, 혈중 creatinine, lactate dehy-drogenase 및 HR의 활성은 cisplatin 단독투여로 증가되었으며 DWP-04의 동시투여로 억제되었고 혈중 SOD의 활성은 cisplatin 단독투여로 억제되던 것이 DWP-04의 동시투여로 증가되었다. 신조직 중 지질 과산화 및 lipofuscin함량은 cis-platin의 투여로 증가되던 것이 DWP-04의 동시투여로 억제 되었다. 활성산소의 생성계인 AD, AO, AH, XO의 활성은 cisplatin의 단독투여로 증가되던 것이 DWP-04의 동시투여로 억제되었다. 활성산소의 해독계인 GST, SOD, CAT, GPx의 활성은 cisplatin의 단독 투여로 억제되던 것이 DWP-04의 투여로 증가되었다. 결 론 : Cisplatin으로 인해 발생한 신장독성 모델에서 DDB, glutathione과 selenium으로 구성된 DWP-04는 신장독성을 경감시키는 결과를 보였다. 이러한 효과는 LPO 및 lipofus-cin의 함량을 경감시키고 활성산소의 생성계 효소의 감소 및 해독계 효소의 증가를 통해 나타난 것으로 사료된다.

Keywords

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