• The Journal of Internal Korean Medicine
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• v.31 no.3
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• pp.620-630
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• 2010

Purpose : The object of this study was to observe the nephroprotective effects of Manjeonmoktong-san(MJMTS), which has traditionally been used as Korean medicine for treating various renal diseases, on cisplatin-induced rat acute renal failure. Methods : At first, three different dosages of MJMTS extract were orally administered once a day for 28 days. On the 23rd day after MJMTS extract treatment, cisplatin was treated. Then, 5 days after cisplatin treatment, all the rats (6 groups of 8 rats each) were checked in the present study. The changes to the body weight, kidney weight, serum BUN and creatinine levels were observed with changes on the kidney MDA and GSH contents. The results were compared with captopril 100mg/kg in which the effects on cisplatin-induced acute renal failures were already confirmed. Results : It showed dramatical decrease on the body weight, increase of serum BUN and creatinine levels were detected in cisplatin control as compared with intact control. In addition marked increase of kidney MDA contests and decrease of kidney GSH contents were also detected in cisplatin control as compared with intact control. it means that cisplatin induced ARF are induced by oxiidative stress and related lipid peroxidation in the present study. However, these ARFs and inhibition of antioxidant effects induced by cisplatin were dose-dependently reduced by treatment of all three different dosages of MJMTS extracts. Conclusion : This study suggests that MJMTS extracts have favorable effects on the cisplatin-induced rat ARF.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.3
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• pp.261-268
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• 2016

$Foxp3^+$ $CD25^+CD4^+$ regulatory T (Treg) cells are crucial for the maintenance of immunological self-tolerance and are abundant in tumors. Most of these cells are chemo-attracted to tumor tissues and suppress anti-tumor responses inside the tumor. Currently, several cancer immunotherapies targeting Treg cells are being clinically tested. Cisplatin is one of the most potent chemotherapy drugs widely used for cancer treatment. While cisplatin is a powerful drug for the treatment of multiple cancers, there are obstacles that limit its use, such as renal dysfunction and the development of cisplatin-resistant cancer cells after its use. To minimize these barriers, combinatorial therapies of cisplatin with other drugs have been developed and have proven to be more effective to treat cancer. In the present study, we evaluated the effect of the combination therapy using methyl gallate with cisplatin in EL4 murine lymphoma bearing C57BL/6 mice. The combinatorial therapy of methyl gallate and cisplatin showed stronger anti-cancer effects than methyl gallate or cisplatin as single treatments. In Treg cell-depleted mice, however, the effect of methyl gallate vanished. It was found that methyl gallate treatment inhibited Treg cell migration into the tumor regardless of cisplatin treatment. Additionally, in both the normal and cisplatin-treated tumor-bearing mice, there was no renal toxicity attributed to methyl gallate treatment. These findings suggest that methyl gallate treatment could be useful as an adjuvant method accompanied with cisplatin therapy.

• Journal of Haehwa Medicine
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• v.26 no.1
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• pp.25-32
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• 2017

Objectives : The purpose of this study is to investigate the effects of Hyangsayangwi-tang (Xiangshayangwei-tang) intravenous herbal acupuncture (HYT-IVHA) on emesis and gastric hypomotility induced by chemotherapy in rats. Methods : The experimental animals were randomly allocated into six groups (normal, cisplatin, saline, HYT-1, HYT-2, HYT-3), and each group included five rats. The rats in the normal group did not receive any treatment. Those in the cisplatin group had no additional treatment after intraperitoneal injection of cisplatin (7 mg/kg). Those in the saline group were injected with saline $0.4m{\ell}$ via the tail vein after the injection of cisplatin. Those in the HYT-1 group, HYT-2 group, HYT-3 group were injected with $0.4m{\ell}$ of Hyangsayangwi-tang (Xiangshayangwei-tang) intravenous herbal acupuncture solution (HYT-IVHAS) via tail vein after the injection of cisplatin, and the concentrations were 0.199 g/kg, 0.066 g/kg, 0.022 g/kg respectively. Then we measured body weight, food intake and kaolin consumption before and at 12h, 24h and 36h after the injection of cisplatin. The remaining amount of food within the rat's stomach was also measured at 36h after cisplatin injection. Results : Kaolin consumption was significantly increased in the cisplatin group compared to the normal group, while significantly reduced in HYT-1, HYT-2, HYT-3 groups compared to the cisplatin group. The remaining amount of food in stomach was significantly increased in the cisplatin group and HYT-1 group compared to the normal group, but significantly reduced in the HYT-3 group compared to the cisplatin group. Conclusions : HYT-IVHA has an therapeutic effect on chemotherapy-induced emesis and gastric hypomotility.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.6
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• pp.1664-1671
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• 2006

Cisplatin is a anti-neoplastic agent which is commonly used for the treatment of solid tumor. Cisplatin activates multiple signal transduction pathways involved in the stress-induced apoptosis in a variety of cell types. Cytotoxicity of cisplatin was detected in rat mesangial cells and the value of $IC_{50}$ is about 20 ${\mu}M$. The treatment of cisplatin to rat mesangial cells showed the apoptotic bodies and DNA fragmentation. The activation of caspase-3, -8, and -9 and proteolytic cleavage of PARP were observed in the rat mesangial cells treated time-dependently with cisplatin. The activation of ERK, p38 and JNK was also observed in the apoptosis induced by cisplatin in rat mesangial cells. The ethanol extract of Bojungbangam-tang (EBJT), a new hergal prescription composed of nine crude drugs, inhibited cisplatin-induced apoptosis in rat mesangial cells. EBJT reduced sub-G1 peak (apoptotic peak) in cisplatin-treated rat mesangial cells. The cisplatin-induced ERK and JNK activation in rat mesangial cells were blocked by EBJT, but EBJT had no effect on p38 activation. Taken together, these results con suggest that EBJT prevents cisplatin-induced apoptotic cell death in rat mesangial cells through inhibition of ERK and JNK activation.

• The Journal of Internal Korean Medicine
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• v.35 no.1
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• pp.92-105
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• 2014

Objectives : Cisplatin is a widely used cancer therapy drug. However, nephrotoxicity resulting in increased oxidative stress is a major side effect of cisplatin chemotherapy, thereby limiting its chemotherapeutic use. Lycium chinense Miller (LCM) has been used as a traditional herbal medicine in various febrile and inflammatory diseases such as night sweat, cough, nosebleed, bronchitis, pulmonary tuberculosis, etc. In this study we investigated the protective and antioxidative potential of LCM against cisplatin-induced nephrotoxicity in rats. Methods : Twenty-four 8-week-old male Wistar rats were divided into four groups: normal untreated; cisplatin treatment only; LCM 10 mg/kg plus cisplatin treatment; and LCM 30 mg/kg plus cisplatin treatment. Twenty-four hours after the last cisplatin injection, all the rats were sacrificed, and serological changes were evaluated. The levels of NF-${\kappa}B$ activity and NOX-4, $p47^{phox}$, $p22^{phox}$, COX-2, iNOS, SOD, catalase expressions were analyzed in Western blot analysis. Results : Cisplatin injection caused an increase in the BUN level, which is a reliable indicator of renal toxicity. The levels of BUN, renal ROS, and renal TBARS were significantly reduced in the LCM groups compared with the cisplatin-only groups. The levels of $p47^{phox}$ and $p22^{phox}$, which are NADPH oxidase subunits, were increased in the cisplatin-only groups, whereas they were decreased in the LCM groups. The levels of renal NF-${\kappa}B$ activity and COX-2, iNOS expressions were increased significantly in the cisplatin-only groups compared with the normal groups, whereas they were decreased in the LCM groups. Compared with the cisplatin-only groups, renal GSH and GSH/GSSG increased in the LCM groups. Also, the administration of LCM increased levels of SOD and catalase as compared with the cisplatin-only groups. Conclusions : These results suggest that LCM protects cisplatin-induced nephrotoxicity via a mechanism that may involves the inhibition of oxidative stress by the activation of antioxidants.

• Journal of Applied Biological Chemistry
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• v.59 no.2
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• pp.113-124
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• 2016

Red ginseng is known to have many beneficial effects. Cisplatin, an effective antineoplastic drug, can cause many side effects like irreversible sensorineural hearing loss and serious tinnitus in humans. This study is aimed to reduce a cisplatin's side effect, nephrotoxicity by fermentated korean red ginseng. Korea ginseng was produced by steaming and dring and fermentation. And mice were divided into 4 groups- (A) normal mice, (B) Vehicle treated cisplatin mice, (C) RG0F0-treated cisplatin mice, (D) RG8F3-treated cisplatin mice. C and D groups were feed each material 200 mg/kg/day during 4 days. And cisplatin 20 mg/kg injected to B, C, and D groups as abdominal injection. After 24 h, blood sample was collected. The kidneys were harvested for histological, immuno histochemical and western blot analysis. 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity was depended on steaming hours. RG0F0 and RG8F3 (ginseng-8 h steamed and fermented by Saccharomyces cerevisiae) were showed antioxidants effect in DPPH and ABTS radical scavenging activity. Component amounts according to steaming hours. 8 h steamed red ginseng had the most ingredients of ginsenoside. Treatments with RG8F3 reduced cisplatin-induced nephrotoxicity in the mice resulting in increase of GSH and decrease of ROS, BUN, creatinine, and inflammatory mediators. This result seems to be involved with the restriction of the inflammation in the kidney. Therefore, fermented red ginseng might have therapeutic efficacy in reduce kidney injury induced by cisplatin treatment.

• Natural Product Sciences
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• v.6 no.4
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• pp.165-169
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• 2000

In vitro cytotoxic activities of cisplatin combined with Chungpesagan-tang or puerarin, which were treated with or without human intestinal bacteria, were measured. When cisplatin was combined with Chungpesagan-tang and its ingredient treated without intestinal bacteria, they did not affect the in vitro cytotoxicity of cisplatin against tumor cell lines. However, when cisplatin was combined with intestinal bacteria-treated Chungpesagan-tang and its ingredients, the cytotoxicities against SNU C4, L1210, A549 and P388 tumor cell lines were synergistically increased. Puerarin, which was isolated from Puerariae Radix, did not show in vitro cytotoxicity. However, its metabolite, daidzein, showed potent cytotoxicity against tumor cell lines and was synergistic by the combined usage of cisplatin. These results suggest that natural glycosides are not only prodrugs which can be transformed to active compounds by intestinal microflora, but the combined usage of cisplatin with natural components, such as daidzein, and herbal medicinal polyprescriptions, such as Chungpesagan-tang, may be a new method for prevention and minimization of the toxicity of cisplatin.

• Journal of Korean Academy of Nursing
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• v.43 no.3
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• pp.361-369
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• 2013

Purpose: The purpose of this study was to examine the effect of anorexia and neuropathic pain induced by cisplatin on hindlimb muscles of rats. Methods: Adult male Sprague-Dawley rats were divided into two groups, a cisplatin-treated group (n=10) and a control group (n=10). In the cisplatin-treated group, cisplatin at a dose of 2 mg/kg was injected intraperitoneally two times a week up to a cumulative dose of 20 mg/kg over 5 weeks, and in the control group saline (0.9% NaCl) was injected intraperitoneally at the same dose and duration as the cisplatin-treated group. At 34 days all rats were anesthetized, after which the soleus and plantaris muscles were dissected. Withdrawal threshold, body weight, food intake, activity, muscle weight, Type I and II fiber cross-sectional areas and myofibrillar protein content of the dissected muscles were determined. Results: Compared with the control group, the cisplatin-treated group showed significant decreases (p<.05) in withdrawal threshold, activity, food intake, body weight, Type I and II fiber cross-sectional areas, myofibrillar protein content and weight of the soleus and plantaris muscles. Conclusion: Muscular atrophy in hindlimb occurs due to anorexia and neuropathic pain induced by the cisplatin treatment.

• Journal of Acupuncture Research
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• v.21 no.2
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• pp.155-166
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• 2004

Objective : The present study was carried out to determine if Semen Plantaginis Herbal-Acupuncture exerts beneficial effect against the cisplatin-induced acute renal failure in rabbits. Method : Semen Plantaginis was selected in the basis of invigorating kidney-QI which can eliminate pathogens. The oxidative stability determined by the Rancimat technique showed higher antioxidative index when compared with control. Rabbits were treated with Semen Plantaginis Herbal-Acupuncture on Shin-shu point for 3 days, followed by cisplatin injection(5mg/kg body weight). Results : Cisplatin injection caused an increase in serum creatinine level, which was accompanied by a reduction in GFR. The fractional excretion of $Na^{+}$, $K^{+}$, glucose and phosphate increased in cisplatin-induced animals, which was partially prevented by Semen Plantaginis Herbal-Acupuncture treatment. Cisplatin injection increased lipid peroxidation, which was not prevented by Semen Plantaginis Herbal-Acupuncture. Conclusions : These results indicate that lipid peroxidation plays a critical role in cisplatin-induced acute renal failure. Semen Plantaginis Herbal-Acupuncture exerts the protective effect against acute renal failure induced by cisplatin, and its effect may be attribued to an antioxidant action.

• The Journal of Internal Korean Medicine
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• v.30 no.4
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• pp.821-831
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• 2009

Purpose : This study was to observe the nephroprotective effects of the traditional prescription, Daebuncheong-eum (DBCE). DBCE has generally been used for treating various renal diseases, including renal failure. Methods : Three different dosages of DBCE extract were orally administered once a day for 28 days. At the 23rd day after DBCE extract treatment, cisplatin was also treated. Then, 5 days after cisplatin treatment, all rats (6 groups of 8 rats each) were sacrificed. Changes on the body weight, kidney weight, serum BUN and creatinine levels were observed, along with changes to the kidney MDA and GSH contents. The results were compared with captopril 100mg/kg, from which the effects on cisplatin-induced acute renal failures have already been confirmed. Results : Cisplatin induced ARF are induced by oxidative stress and related lipid peroxidation in the present study. However, these ARFs and inhibition of antioxidant effects induced by cisplatin were dose-dependently reduced by treatment of all three different dosages of DBCE extracts. Conclusion : This study suggests that DBCE extracts show favorable effects on cisplatin-induced rat ARF.