유제한성 병기의 소세포 폐암에서 3주 간격으로 시행된 irinotecan과 cisplatin을 이용한 과다분할 방사선 동시 요법

이정은 ( Jeong Eun Lee ),박희선 ( Hee Sun Park ),정성수 ( Sung Soo Jung ),김주옥 ( Ju Ock Kim ),조문준 ( Moon June Cho ),김진환 ( Jin Hwan Kim ),이충식 ( Choong Sik Lee ),김선영 ( Sun Young Kim ) 대한결핵 및 호흡기학회 2007 Tuberculosis and Respiratory Diseases Vol.63 No.2

배경: Irinotecan hydrochloride는 topoisomerase I inhibitor로서 소세포 폐암에 효과적인 약제로 알려져 있다. Irinotecan은 cisplatin과 더불어 방사선감작물질로 작용하기도 한다. 본 연구는 이전에 치료받은 경험이 없는 제한성 병기의 소세포 폐암 환자에서 irinotecan과 cisplatin(IP)의 방사선 동시화학요법의 효과를 평가하기 위하여 시행되었다. 방법: 2002년 12월부터 2004년 11월까지 충남대학교 병원에서 새로이 제한성 병기의 소세포 폐암으로 진단된 24명의 환자들을 대상으로 하였다. Irinotecan 60 mg/m2을 제 1일과 제 8일째 투여하였고 cisplatin 60 mg/m2을 제 1일째 투여하였으며 매 3주 간격으로 시행되었다. 제 3차 항암화학요법을 시작하는 날과 동시에 과다 분할방사선 치료(twice-daily thoracic irradiation; 45 Gy total)을 시작하였다. 예방적 전 뇌 방사선 조사(Prophylactic cranial irradiation)가 방사선 동시화학요법이 끝난 후 완전반응(complete response)을 나타낸 환자에서 시행되었다. 제 2차 항암요법과 제 6차 항암요법이 끝난 후에 흉부 전산화 단층촬영과 기관지경 등을 통한 병기의 재평가가 이루어졌다. 결과: 병기의 재평가는 19명의 환자에게 이루어졌다. 중앙 추적관찰기간은 12.5개월이고 전체 99회의 항암치료가 시행되었다. 평균 한 환자당 5.2회의 항암치료가 시행되었다. 실제 용량강도는 cisplatin 19.6 mg/m2/week과 irinotecan 38.2 mg/m2/week이었다. 9명의 환자가 완전반응을 보였고 10명의 환자가 부분반응(partial response)을 보여서 전체 반응률은 95%였다. 3에서 4도의 혈액학적 독성은 백혈구 감소증(35% of cycles), 빈혈(7% of cycles), 혈소판 감소증(7% of cycles) 등으로 나타났다. 3에서 4도의 비 혈액학적 독성은 설사(5% of cycles)였다. 3에서 4도의 방사선 식도염(10% of patients)을 제외하고는 과다 분할 방사선 치료를 이용한 방사선 동시 화학요법의 기존의 방법과 독성 면에서는 큰 차이가 없었다. 치료와 관련된 사망은 관찰되지 않았다. 평가가 가능한 환자들에서 1년 생존율과 2년 생존율은 각각 89% (16/18)와 47% (9/18)였다. 결론: 3주 간격으로 시행된 irinotecan과 cisplatin을 이용한 과다분할 방사선 동시 요법은 제한성 병기의 소세포 폐암 환자에서 부작용은 높지 않으면서 효과적인 치료법으로 고려될 수 있을 것이다. (Tuberc Respir Dis 2007; 63: 154-164) Background: Irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against small-cell lung cancer. Irinotecan also can act as a potential radiation sensitizer along with cisplatin. To evaluate efficacy and toxicity of irinotecan plus cisplatin (IP) with concurrent thoracic radiotherapy, we conducted a phase II study of IP followed by concurrent IP plus hyperfractionated thoracic radiotherapy in patients with previously untreated limited-stage small-cell lung cancer. Methods: Twenty-four patients with previously untreated small-cell lung cancer were enrolled onto the study since November 2004. Irinotecan 60 mg/m2 was administered intravenously on days 1 and 8 in combination with cisplatin 60 mg/m2 on day1 every 21 days. From the first day of third cycle, twice-daily thoracic irradiation (total 45 Gy) was given. Prophylactic cranial irradiation was given to the patients who showed complete remission after concurrent chemoradiotherapy. Restaging was done after second and sixth cycle with chest CT and/or bronchosocpy. Results: Up to November 2004, 19 patients were assessable. The median follow-up time was 12.5 months. A total of 99 cycles (median 5.2 cycles per patient) were administered. The actual dose intensity values were cisplatin 19.6 mg/m2/week and irinotecan 38.2 mg/m2/week. Among the 19 patients, the objective response rate was 95% (19 patients), with 9 patients (47%) having a complete response (CR). The major grade 3/4 hematological toxicities were neutropenia (35% of cycles), anemia (7% of cycles), thrombocytopenia (7% of cycles). Febrile neutropenia was 4% of cycles. The predominant grade 3/4 non-hematological toxicities was diarrhea (5% of cycles). Toxicities was not significantly different with concurrent administration of irinotecan and cisplatin with radiotherapy, except grade 3/4 radiation esophagitis (10% of patients). No treatment-related deaths were observed. The 1-year and 2-year survival rate of eligible patients was 89% (16/18) and 47% (9/18), respectively. Conclusion: Three-week schedule of irinotecan plus cisplatin followed by concurrent IP plus hyperfractionated thoracic radiotherapy is an effective treatment for limited disease small-cell lung cancer, with acceptable toxicity.

Cisplatin에 의한 뇌세포사멸에서 補中免疫丹의 방어효과

유경태,문석재,원진희,김동웅,이종덕,원경숙,문구 대한동의생리학회,대한동의병리학회 2003 동의생리병리학회지 Vol.17 No.2

This study was designed to investigate the protective effect of Bojungmyunyuk-dan(BJMY-Dan) on the cisplatin-induced cytotoxicity of primary rat astrocytes. BJMY-Dan is an oriental herbal prescription for its ability to recover protectve effects against anti-cancer chemotherapies. After astrocytes were treated cisplafin, MTT assay was performed for cell viability test. To explore the mechanism of cytotoxicity, I used the several measures of apoptosis to determine whether this processes was involved in cisplatin-induced cell damage in astrocytes. AJso, astrocytes were treated with BJMY-Dan and then, followed by the addition of cisplatin. Cisplatin decreased the viability of astrocytes in a dose and time-dependent manner. BJMY-Dan increased the viability of astrocytes treated cisplatin. Astrocytes treated cisplatin were revealed as apoptosis characterized by nuclear staining and flow cytometry. BJMY-Dan protected astrocytes from cisplatin-induced nuclear fragmentation and chromatin condensation. Also, caspase-3 and caspase-9 proteases were activated in astrocytes by cisplatin. BJMY-Dan inhibited the activation of caspase proteases in cisplatin-treated astrocytes. Cleavage of [poly(ADP-ribose) polymerase](PARP) was occurred at 12hr after treatment of cisplatin in astrocytes. BJMY-Dan recovered the cleavage of PARP in cisplatin-treated astrocytes. Also, BJMY-Dan inhibited the activation of pro-apoptotic factor, Bak by cisplatin. Lastly, astrocytes stained with JC-1 and Rhodamine 123 were photographed by fluorescence microscope to visualize changes of mitochondrial membrane permeability transition(MPT) during treatment with cisplatin for 24hr. BJMY-Dan recovered the change of MPT by cisplatn in astrocytes. According to above results, BJMY-Dan may protect astrocytes from cytotoxicity induced by chemotherapeutic agents, including cisplatin.

Cisplatin에 의한 기니픽와우 외유모세포의 Ca²⁺전류의 변화

정종우,김종선 대한이비인후과학회 1998 대한이비인후과학회지 두경부외과학 Vol.41 No.5

Paricalcitol prevents cisplatin-induced renal injury by suppressing apoptosis and proliferation

Park, J.W.,Cho, J.W.,Joo, S.Y.,Kim, C.S.,Choi, J.S.,Bae, E.H.,Ma, S.K.,Kim, S.H.,Lee, J.,Kim, S.W. North-Holland ; Elsevier Science Ltd 2012 european journal of pharmacology Vol.683 No.1

The present study was performed to examine whether paricalcitol may prevent the cisplatin-induced kidney injury. Furthermore, potential molecular mechanisms underlying the protective effect of paricalcitol were explored. Male Sprague-Dawley rats were treated with vehicle (n=12), cisplatin (n=12, 6mg/kg/day, i.p.), or cisplatin+paricalcitol (n=12, 0.2μg/kg/day, s.c.) for 4days. In another series of experiment, HK-2 cells were treated with cisplatin (50μM), with or without paricalcitol (0.2ng/ml). Paricalcitol counteracted the cisplatin-induced decline in renal function. Paricalcitol also suppressed the expression of TGF-β1, Smad signaling, and the subsequent epithelial-to-mesenchymal process in cisplatin-treated rats. The expression of P-p53 and p21 was increased in cisplatin-induced nephropathy. These changes were completely prevented or significantly attenuated with paricalcitol co-treatment. The expression of p27<SUP>kip1</SUP> was increased in cisplatin-treated rats, which was, however, further augmented by the paricalcitol co-treatment. In HK-2 cells, cisplatin increased the expression of p-ERK½ and P-p38. Cisplatin also increased the expression of fibronectin and CTGF. Cisplatin increased the expression of pro-apoptotic markers. The expression of CDK2 and Cyclin E as well as that of PCNA was increased. These changes were completely prevented or significantly attenuated by the paricalcitol pretreatment. In contrast, cisplatin increased the expression of p27<SUP>kip1</SUP>, which was further augmented by the paricalcitol-pretreatment. These results suggest that paricalcitol may ameliorate cisplatin-induced renal injury by suppressing the fibrotic, apoptotic and proliferative factors. Its underlying mechanisms may include inhibition of TGF-β1, mitogen-activated protein kinase signaling, p53-induced apoptosis, and augmentation of p27<SUP>kip1</SUP>.

Resveratrol enhances cisplatin-induced apoptosis in human hepatoma cells via glutamine metabolism inhibition

( Zhaoyuan Liu ),( Qing Peng ),( Yang Li ),( Yi Gao ) 생화학분자생물학회(구 한국생화학분자생물학회) 2018 BMB Reports Vol.51 No.9

Cisplatin is one of the most effective chemotherapeutic drugs used in the treatment of HCC, but many patients will ultimately relapse with cisplatin-resistant disease. Used in combination with cisplatin, resveratrol has synergistic effect of increasing chemosensitivity of cisplatin in various cancer cells. However, the mechanisms of resveratrol enhancing cisplatininduced toxicity have not been well characterized. Our study showed that resveratrol enhances cisplatin toxicity in human hepatoma cells via an apoptosis-dependent mechanism. Further studies reveal that resveratrol decreases the absorption of glutamine and glutathione content by reducing the expression of glutamine transporter ASCT2. Flow cytometric analyses demonstrate that resveratrol and cisplatin combined treatment leads to a significant increase in ROS production compared to resveratrol or cisplatin treated hepatoma cells alone. Phosphorylated H2AX (γH2AX) foci assay demonstrate that both resveratrol and cisplatin treatment result in a significant increase of γH2AX foci in hepatoma cells, and the resveratrol and cisplatin combined treatment results in much more γH2AX foci formation than either resveratrol or cisplatin treatment alone. Furthermore, our studies show that over-expression of ASCT2 can attenuate cisplatin-induced ROS production, γH2AX foci formation and apoptosis in human hepatoma cells. Collectively, our studies suggest resveratrol may sensitize human hepatoma cells to cisplatin chemotherapy via glutamine metabolism inhibition. [BMB Reports 2018; 51(9): 474-479]

Cisplatin에 의해 신독성이 유발된 백서에서 iNOS의 발현 및 iNOS억제제의 효과

이두형,명순철,김영선 大韓泌尿器科學會 1999 Korean Journal of Urology Vol.40 No.2

Cisplatin을 포함한 항암치료를 받은 소아에서 이독성

장희진,조형래,이재희,배근욱,서종진,문형남,임호준 대한소아청소년과학회 2010 Clinical and Experimental Pediatrics (CEP) Vol.53 No.2

Purpose:Cisplatin is highly effective for the treatment of solid tumors in children. However, the clinical use of cisplatin is limited by its ototoxicity. The aim of this study was to evaluate the ototoxicity in children treated with cisplatin. Method:We performed a single institution retrospective analysis of pediatric oncology patients who received cisplatin therapy between January 2001 and January 2008. Thirty-seven patients with sufficient medical and audiologic data were included in this study. Results:The median age at the time of diagnosis was 10.7 (range 3.8–16.7) years. There were 16 males and 21 females. The underlying diseases were osteosarcoma (15 cases), medulloblastoma (14 cases), germ cell tumors (7 cases), and hepatoblastoma (1 case). The median individual dose was 100 mg/m2/cycle (56-200). The median cumulative dose was 480 mg/m2 (200-1,490). Sixteen patients (43%) received cranial radiotherapy. Of the 37 patients, 17 developed hearing loss, leading to an overall incidence of 46%. Logistic regression showed that age at treatment (P=0.04) and cumulative dose of cisplatin (P=0.005) were the significant risk factors in predicting hearing loss in children treated with cisplatin. In all the patients who had hearing loss, there was neither improvement nor aggravation during the follow-up (3–68 months). Conclusion:The cumulative dose of cisplatin (>500 mg/m2) and younger age at treatment (<12 years) were 2 most important risk factors for ototoxicity in patients treated with cisplatin. Serial audiometric evaluations are needed in the patients with risk factors during and after cisplatin treatment. 목적:Cisplatin은 소아 고형종양의 치료에 효과적으로 사용되는 항암제이다. 그러나 이독성의 발생은 cisplatin의 사용을 제한하고 있다. 이에 저자들은 cisplatin을 투여 받은 소아 고형종양 환아에서 발생한 이독성의 특징과 관련 인자들을 알아보고자 하였다. 방법:2001년 1월부터 2008년 1월까지 서울아산병원 소아과에서 고형종양으로 cisplatin을 포함한 항암치료를 받았고, 청력검사를 시행 받은 37명의 환아를 대상으로 하였다. 대상 환아의 진단 시 나이, 성별, 진단명, 두개 방사선 조사 여부, 그리고 cisplatin의 개별용량 및 누적량을 조사하였다. 청력검사는 항암 치료 전과 종료 후에 순음청력검사를 시행하였다. 결과:37명 환아의 기저 질환은 골육종 15례, 수모세포종 14례, 생식세포종양 7례, 그리고 간모세포종 1례이었다. 진단 시 정중 연령은 10.7세(3.8-16.7)이었고 남아가 16명, 여아가 21명이었다. 투여된 cisplatin의 정중 개별용량은 100 mg/m2/cycle (56-200), 그리고 정중 누적량은 480 mg/m2 (200-1,490)이었다. 16명(43%)의 환아가 두개 방사선 조사를 받았다. 치료 종료 후 시행한 청력검사에서 청력장애를 보인 환아들은 17명(46 %)이었다. 진단 시 나이가 12세 미만인 군(P=0.04)과 cisplatin 누적량 500 mg/m2 이상인 군(P=0.005)에서 이독성의 발생이 유의하게 증가하였다. 환아의 성별, 진단명, 두개 방사선 조사 여부, 그리고 cisplatin의 개별용량과 이독성의 발생과는 유의한 차이는 없었다. 정중 22개월(3-68)의 추적관찰 기간 동안 청력장애를 보인 16명의 환아들은 장애가 호전되지 않았다. 결론:진단 시 12세 미만과 누적량 500 mg/m2 이상의 cisplatin 투여받은 환아군에서 cisplatin에 의한 이독성의 빈도가 유의하게 증가하였으며 청력장애 발생 시에는 치료 종료 후에도 호전되지 않았다. 이에 위험인자를 지닌 환아들의 주기적인 청력검사가 필요하며, 이독성 발생의 예방에 대한 연구도 필요할 것으로 생각된다.

The relationship between cisplatin resistance and histone deacetylase isoform overexpression in epithelial ovarian cancer cell lines

김민규,박장호,최원호,박정열,남주현,김종혁 대한부인종양학회 2012 Journal of Gynecologic Oncology Vol.23 No.3

Objective: To investigate the relationship between cisplatin resistance and histone deacetylase (HDAC) isoform overexpression in ovarian cancer cell lines. Methods: Expression of four HDAC isoforms (HDAC 1, 2, 3, and 4) in two ovarian cancer cell lines, SKOV3 and OVCAR3, exposed to various concentrations of cisplatin was examined by western blot analyses. Cells were transfected with plasmid DNA of each HDAC. The overexpression of protein and mRNA of each HDAC was confirmed by western blot and reverse transcriptase-polymerase chain reaction analyses, respectively. The cell viability of the SKOV3 and OVCAR3 cells transfected with HDAC plasmid DNA was measured using the cell counting kit-8 assay after treatment with cisplatin. Results: The 50% inhibitory concentration of the SKOV3 and OVCAR3 cells can be determined 15-24 hours after treatment with 15 μg/mL cisplatin. The expression level of acetylated histone 3 protein in SKOV3 cells increased after exposure to cisplatin. Compared with control cells at 24 hours after cisplatin exposure, the viability of SKOV3 cells overexpressing HDAC 1 and 3 increased by 15% and 13% (p<0.05), respectively. On the other hand, OVCAR3 cells that overexpressed HDAC 2 and 4 exhibited increased cell viability by 23% and 20% (p<0.05), respectively, compared with control cells 24 hours after exposure to cisplatin. Conclusion: In SKOV3 and OVCAR3 epithelial ovarian cancer cell lines, the correlation between HDAC overexpression and cisplatin resistance was confirmed. However, the specific HDAC isoform associated with resistance to cisplatin varied depending on the ovarian cancer cell line. These results may suggest that each HDAC isoform conveys cisplatin resistance via different mechanisms. Objective: To investigate the relationship between cisplatin resistance and histone deacetylase (HDAC) isoform overexpression in ovarian cancer cell lines. Methods: Expression of four HDAC isoforms (HDAC 1, 2, 3, and 4) in two ovarian cancer cell lines, SKOV3 and OVCAR3, exposed to various concentrations of cisplatin was examined by western blot analyses. Cells were transfected with plasmid DNA of each HDAC. The overexpression of protein and mRNA of each HDAC was confirmed by western blot and reverse transcriptase-polymerase chain reaction analyses, respectively. The cell viability of the SKOV3 and OVCAR3 cells transfected with HDAC plasmid DNA was measured using the cell counting kit-8 assay after treatment with cisplatin. Results: The 50% inhibitory concentration of the SKOV3 and OVCAR3 cells can be determined 15-24 hours after treatment with 15 μg/mL cisplatin. The expression level of acetylated histone 3 protein in SKOV3 cells increased after exposure to cisplatin. Compared with control cells at 24 hours after cisplatin exposure, the viability of SKOV3 cells overexpressing HDAC 1 and 3 increased by 15% and 13% (p<0.05), respectively. On the other hand, OVCAR3 cells that overexpressed HDAC 2 and 4 exhibited increased cell viability by 23% and 20% (p<0.05), respectively, compared with control cells 24 hours after exposure to cisplatin. Conclusion: In SKOV3 and OVCAR3 epithelial ovarian cancer cell lines, the correlation between HDAC overexpression and cisplatin resistance was confirmed. However, the specific HDAC isoform associated with resistance to cisplatin varied depending on the ovarian cancer cell line. These results may suggest that each HDAC isoform conveys cisplatin resistance via different mechanisms.

Cisplatin에 의해 유발된 급성신부전에 단삼추출액이 미치는 영향

김충희,박희성,정장용 진주산업대학교 농업기술연구소 2005 農業技術硏究所報 Vol.18 No.-

한의학에서 강장약, 통경약, 진통약, 항염약, 지혈약으로 월경불순, 복통, 폐경, 산후통 등에 효과가 있다고 알려진 단삼(Salvia mulitorrhiza Bunge)이 cisplatin에 의해 유발된 신장의 세포손상에 대하여 항산화작용과 신장의 기능에 미치는 영향에 대하여 조사한 결과 다음과 같은 결과를 얻었다. 1. 단삼 추출액이 cisplatin에 의하여 유발된 신피질 절편의 독성효과에 대한 효과를 알아 보기위한 실험으로 300mM cisplatin에 노출시켰을 때 단삼 추출액 0.05%, 0.1%를 함께 첨가한 군이 LDH 유출 및 지질과산화를 유의성 있게 감소시켰다. 2. 단삼 추출액 0.3g/kg을 7일간 전처리 한 다음 cisplatin 5㎎/kg을 복강투여한 후 24시간 뒤에 혈액을 채취하여 혈청 BUN과 creatinine 농도를 측정한 결과, 단삼 추출액을 전처리 한 군에서 cisplatin 단독처리한 군보다 신장의 BUN 및 creatinine 제거율이 유의성 있게 높게 나타났다. 이상의 결과로 볼 때 단삼 추출액은 cisplatin에 의하여 유발된 신장의 독성효과에 대하여 항산화작용과 세포보호 작용을 나타내며, 신장의 기능에도 영향을 미쳐 BUN과 creatinine 제거율도 높게 나타내었다. 따라서 단삼이 신장의 세포손상이나 질환이 있을 경우 보호효과를 나타낼 것으로 생각되며, 이러한 계기로 단삼을 대량 재배하여 신장보호를 위한 기능성 식품을 개발할 수 있다면 신장기능부전환자나 단삼재배 농가에 큰 도움을 줄 수 있으리라 생각한다. Salvia mulitorrhiza Bunge is known to be effective on healthiness drug, pain-killing drug, anti-inflammation, hemostatic agent, irregular menstruaction, abdominal pain, menopause, after parturition pain activity in oriental medicine. In addition of the effects, I further investigated the effect Salvia mulitorrhiza Bunge extract(SMBE) on the antioxidant effect on a renal cortical slices cell and kidney protecting effects. The results were as follows. 1. When renal cortical slices separated from a rabbit's kidney were treated with oxidant 300μM cisplatin in the presence of 0.05% or 0.1% SMBE at 37℃ for 60min. Cisplatin caused an increase a LDH release and lipid peroxidation. Cisplatin also induced a increase in LDH release and lipid peroxidation. SMBE significant prevented cisplatin-induced increase in LDH release and lipid peroxidation. 2. Pretreatment with 0.3g/kg SMBE for seven day and treatment with 5mg/kg cisplatin by the intraperitoneal injection. After 24hours, BUN and creatinine in serum were measured. The results were that the pretreatment group with SMBE showed a significant clearance rate of BUN and creatinine in the kidney than the administering single agent group of cisplatin. These results indicate that lipid peroxidation plays a critical in cisplatin-induced acute renal failure. SMBE exerts the protective effect against acute renal failure induced by cisplain, and its effect may be attributed to an antioxidant action. Furthermore I suggest the development of functional food with SMBE for the kidney tissue damage or renal incompletion in human.

Cisplatin에 의한 마우스의 급성 신부전 완화에 대한 Endothelin A 수용체의 차단 효과

김일두,안도환 고신대학교의과대학 2007 고신대학교 의과대학 학술지 Vol.22 No.1

Background : Acute renal failure (ARF) can be pathophysiologically classified to hemodynamically-mediated or nephrotoxic type, and in either case, endothelin (ET)-1 expression is enhanced in renal tissues. Hemodynamically-mediated ARF is known to be mitigated by ETA receptor (ETAR) blocker but not ETB receptor (ETBR) blocker. There is poorly understood on mitigation of renal injuries by ETAR or ETBR blockade in nephrotoxic ARF. Therefore, This study examined whether nephrotoxic ARF induced by cisplatin is functionally and/or histologically ameliorated by ETAR blocker BQ123. Materials and Methods : Male C57BL/6 mice are intraperitoneally injected with vehicle (saline), cisplatin or cisplatin+BQ123. Cisplatin was single administrated with a dose of 16 mg/kg/day and BQ123 with a dose of 24 mg/kg/day once a day for 4 consecutive days including a baseline day. Urine flow, excretion of electrolytes and protein, and creatinine clearance were measured. Histological changes were observed through periodic acid-Schiff stain. Real time RT-PCR was performed to evaluate expression of ET-1 and ETAR mRNA. Distribution of ET-1 peptide within renal cortex was examined by immunohistochemistry. Results : Body weight, urine flow, excretion of protein, Na, K, and creatinine clearance tended to decrease by cisplatin administration compared to vehicle treatment, but these parameters did not return to the normal level by combined administration of cisplatin and BQ123. Necroses of several proximal tubules were observed in the cisplatin group, indicating that mild nephrotoxicity occured. In the cisplatin+BQ123 group, this change seemed to increase, rather than decrease. Expression of ET-1 and ETAR mRNA was 6 and 2-fold higher in the cisplatin group than the saline group, respectively. BQ123 treatment reversed ETAR mRNA expression to the basal level but not ET-1 mRNA. Immnuoreactive ET-1 was mainly distributed within proximal tubule cells in all three groups. Immunoreactivity of ET-1 was enhanced in both the cisplatin group and the cisplatin+BQ123 group compared to the saline group, but was similar between the cisplatin group and the cisplatin+BQ123 group. Conclusion : Administration of a ETAR blocker BQ123 in cisplatin-induced nephrotoxic ARF is not likely to be effective in amelioration of renal injuries.