[논문]Preventive effect of fermented black ginseng against cisplatin-induced nephrotoxicity in rats

Jung, Kiwon; An, Jun Min; Eom, Dae-Woon; Kang, Ki Sung; Kim, Su-Nam

doi:10.1016/j.jgr.2016.03.001

[국내논문] Preventive effect of fermented black ginseng against cisplatin-induced nephrotoxicity in rats 원문보기

Journal of ginseng research = 高麗人參學會誌, v.41 no.2, 2017년, pp.188 - 194

Jung, Kiwon (College of Pharmacy, CHA University) , An, Jun Min (GINSENG BY PHARM Co., Ltd.) , Eom, Dae-Woon (Department of Pathology, University of Ulsan College of Medicine, Gangneung Asan Hospital) , Kang, Ki Sung (College of Korean Medicine, Gachon University) , Kim, Su-Nam (Natural Products Research Institute, Korea Institute of Science and Technology)

Abstract ▼ AI-Helper

Background: Fermented black ginseng (FBG) is processed ginseng by the repeated heat treatment and fermentation of raw ginseng. The protective effect and mechanism of FBG on cisplatin-induced nephrotoxicity was investigated to evaluate its therapeutic potential. Methods: The free radical scavenging activity of FBG was measured using 1,1-diphenyl-2-picrylhydrazyl (DPPH). In addition, the protective effect against cisplatin-induced renal damage was tested in rats. FBG was orally administered every day at a dose of 150 mg/kg body weight for 10 d, and a single dose of cisplatin was administered intraperitoneally (7.5 mg/kg body weight) with 0.9% saline on the $4^{th}$ d. Results: The DPPH radical-scavenging activity of FBG ($IC_{50}=384{\mu}g/mL$) was stronger than that of raw ginseng. The improved DPPH radical-scavenging activity was mediated by the generation phenolic compounds. The decreased cell viability by cisplatin was recovered significantly after treatment with FBG in a dose-dependent manner. Then, the protective effect of FBG on cisplatin-induced oxidative renal damage was investigated in rats. The decreased creatinine clearance levels, which are a reliable marker for renal dysfunction in cisplatin-treated rats, were reduced to the normal level after the administration of FBG. Moreover, FBG showed protective effects against cisplatin-induced oxidative renal damage in rats through the inhibition of $NF-{\kappa}B/p65$, COX-2, and caspase-3 activation. Conclusion: These results collectively show that the therapeutic evidence for FBG ameliorates the nephrotoxicity via regulating oxidative stress, inflammation, and apoptosis.

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문제 정의

Although the efficacy of FBG is poorly understood, augmentation of antioxidant activity and its beneficial effect on vascular dementia have recently been reported [28,29]. The objective of this study is to evaluate how FBG shows renoprotective efficacy against cisplatin-induced renal oxidative stress.

제안 방법

FBG (250–500 μg/mL) ameliorated cisplatin-induced nephrotoxicity up to 80% of the control level, and further in vivo studies were carried out with FBG.

데이터처리

The quantitative data were expressed as means ± standard deviation. Statistical significance was determined using the analysis of variance followed by a multiple comparison test with a Bonferroni adjustment. A p value < 0.

이론/모형

18M EDTA, which were then centrifuged at 3,000 g for 5 min at 4℃. The plasma creatinine levels were determined using a rate-blanked kinetic Jaffe method. Creatinine clearance was calculated on the basis of the urinary creatinine (Cr), serum Cr, urine volume, and body weight using the following equation:
(C) Effects on cisplatin-induced damage in LLC-PK1 cells. The total phenolic contents and antioxidant effects of samples were determined using the FolineCiocalteu and DPPH radical scavenging assays. LLC-PK1 cells were pretreated with various concentrations (up to 500 μg/mL) of the ginsengs for 2 h, and then 25μM cisplatin was further treated for 24 h.
LLC-PK1 cells were pretreated with various concentrations (up to 500 μg/mL) of the ginsengs for 2 h, and then 25μM cisplatin was further treated for 24 h. Cell viability was assessed using the MTT assay. * p < 0.
The total phenolic contents of samples were determined using the Folin–Ciocalteu method [30].

성능/효과

Therefore, caspase inhibitors have the potential to minimize uncontrolled apoptosis in cisplatin-induced nephropathy [43]. Our results also showed significant increases in cleaved caspase-3 expression levels of the cisplatin-treated rat kidney, but its elevated level was significantly reduced after FBG administration. Similarly, the elevated NF-κB/p65 and COX-2 protein expressions, which are reliable markers of inflammation in cisplatin-treated rat kidney [44], were lowered nearly back to its normal levels.

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