• Clinical and Experimental Pediatrics
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• v.53 no.2
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• pp.210-214
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• 2010

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 3.8-6.7) 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 $100mg/m^2$/cycle (56-200). The median cumulative dose was $480mg/m^2$ (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 (3-8 months). Conclusion : The cumulative dose of cisplatin (>$500mg/m^2$) 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.

• Environmental Analysis Health and Toxicology
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• v.14 no.1_2
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• pp.13-19
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• 1999

Cisplatin is an inorganic complex formed by a central atom of platinum surrounded by chlorine and ammonia atoms in the cis position in the horizontal plane, Cisplatin is one of the most effective anticancer drug, widely used against various tumor such as testicular tumor, brain tumor, ovary tumor, bladder carcinoma, colon cancer etc. However its clinical use has been limited by nephrotoxicity, ototoxicity , gastrointestinal disturbances, myeloscrppression and allergic reactions. In these toxicities, dose related and cumulative nephrotoxicity is the major dose limit factor. So, to evaluate the protective effect of aspalactone on cisplatin nephrotoxicity in rats, both compounds were given intraperitoneally, Protective effects of aspalactone against nephrotoxicity of cisplatin were observed when aspalactone was administered to rats 1hr beforecisplatin injection. Hepatotoxicity induced by combination treatment of cisplatin and aspalactone was not observed. The present results indicate that aspalactone may provide protection against cisplatin nephrotoxicity, when it is given 1hr before cisplatin injection.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2002.07a
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• pp.97-102
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• 2002

Life Science Research Center of SK Chemicals has developed a 3rd-generation anticancer platinum drug for the first time in the nation′s 100-year-old pharmaceutical industry. The Korea Food and Drug Administration (KFDA) approved the sale of "Sunpla" (code name SKI 2053R, general name : Heptaplatin) on July 14, 1999 for the treatment of advance, metastatic gastric cancer. Cisplatin, the 1 st-generation anticancer drug, which was developed by Bristol-Myers of the United States in 1976, is one of the most potent anticancer drugs and is a major component of combination chemotherapy for a variety of human cancers. However its clinical usefulness has frequently been limited not only by undesirable side effects such as severe renal toxicity, nausea, vomiting, ototoxicity, and neurotoxicity but also by the development of resistance. Carboplatin, the 2nd-generation anticancer platinum drug, which was also developed by Bristol-Myers in 1986, has modified the problems of the renal and gastrointestinal toxicities of cisplatin. Carboplatin, however, has no enhanced therapeutic efficacy over cisplatin and does not possess the property to overcome cross-resistance to cisplatin.

• Proceedings of the KOR-BRONCHOESO Conference
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• 1987.05a
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• pp.5.1-5
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• 1987

Cisplatin (cis-dichlorodiamine platinum II)은 두경부 및 고환의 악성종양에 아주 효과적이라고 알려져 있다. 그러나 이 약물은 이독성 및 신독성이 이미 임상연구로 발표되어 있으며 신독성은 cisplatin 투여시 이뇨제 및 수액의 투여로 그 정도 및 빈도는 감소시킬 수 있지만 이독성은 감소시키지 못한다. Cisplatin에 의한 이독성은 보통 자각적으로 나타나지 않는데 이는 내이 와우각의 회전중 저부에서 일어나며 또한 외유모세포의 최외측열에서 일어난다고 동물실험에서 밝혀진 바 있다. 본 교실에서는 cisplatin의 이독성을 관찰하기 위하여 1회에 cisplatin 60~80 mg/$m^2$을 투여한 두경부 악성종양환자를 대상으로 투여전후의 청력을 비교 관찰하였다. 1) 청력은 대부분 10㏈ 이내의 손실례가 많았다. 2) 최대청력손실이 있는 주파수는 8KHz, 4KHz의 순으로 주로 고음역에서 발생하였다. 3) 신독성은 전례에서 관찰되지 않았다.

• Journal of The Korean Society of Clinical Toxicology
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• v.3 no.2
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• pp.119-121
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• 2005

Sodium bromate or potassium bromate has been used as hair cold neutralizer. Sodium bromate intoxications occurred in children incidentally early days of marketing, but recently in adult suicidally. This chemical intoxication result in renal failure, ototoxicity, neurotoxicity, hemolytic anemia and so on. We experienced a 39-year-old woman of hairdresser with non-oliguric acute renal failure after ingestion hair neutralizer 500 ml. She received hemodialysis 3 times and discharged without complication on 8th admission days.

• Research in Vestibular Science
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• v.17 no.4
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• pp.130-133
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• 2018

There are a number of reports on the pathologies of vestibular disorders. However, these studies included only a few examples, which were not quantitative but merely anecdotal or descriptive. However, a single tissue section may be relevant to a specific disease in multiple ways. The histopathological characteristics of common peripheral vestibulopathies, including benign paroxysmal positional vertigo, $M{\acute{e}}ni{\grave{e}}re^{\prime}s$ syndrome, labyrinthitis, vestibular neuritis, and ototoxicity, have been described. A recent study validated a new quantitative method for determining vestibular otopathology. Detailed quantitative analyses of vestibular pathology are required to obtain a deeper understanding of the vestibular system. Such studies will likely reveal the pathophysiological causes of specific diseases by elucidating the correlations between structural and functional features. Therefore, histopathological studies of vestibular disorders should be performed.

• Proceedings of the KOR-BRONCHOESO Conference
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• 1982.05a
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• pp.17.1-17
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• 1982

In 1965, Rosenberg reported that platinum compounds not only inhibit growth and cell division of E. coli but also has anti-tumor activity. Since then, through animal and clinical experiments by Welsch(1971), Speer(1972), Rossof(1972), Hill(1974), and Wittes(1975), it was proved that Cis-platinum has excellent supressive effects on malignant tumor, especially on head and neck cancer. Accordingly, Cis-platinum is now widely used, sometimes without any other durg, or sometimes with Bleomycin and Methotrexate etc. Inspite of the strong anticancer effect, the use of Cis-platinum is quite often discouraged because of the reports that Cis-platinum causes auditory impairment at high frequencies above the speech range due to inner ear damage and irreversible change in the renal tubules. Since Kohonen et al(1965), Standnicki et al(1974) reported that Cisplatinum has toxic effects at the basal turn of the cochlea using guinea pig, many studies on ototoxicity after infusion of Cis-platinum have been carried out using animals. But the studies on ototoxicity in human beings can hardly be found except in reports by Piel et al(1974) and Hong et al (1979). So the authors did a study which tried to clarify the ototoxic effect by comparing the hearing level after infusion of Cis-plastinum with the hearing level before infusion of Cis-plastinum in 30 patients who was treated with Cis-platinum and admitted to the dept. of otolaryngology of Yonsei University Hospital during 2 years and a half from July. 1979 to March. 1982 and the following results were obtained. 1) The results of auditory evaluation, using the pure tone average, hearing loss of 4kHz and 8kHz, Speech Reception Threshold, PB score, SISI showed that the difference of dosage does not change the hearing level after infusion of Cis-platinum and before infusion of Cis-platinum. 2) Cis-platinum had no effect on the hearing level of patients with conductive hearing loss, or with sensorineural hearing loss, as well as with normal hearing level. 3) The infusion of Cis-platinum did not cause any change in creatinine clearance, creatinine, uric acid, but only one case showed that Cis-platinum caused severe nephrotoxicity. 4) The infusion of Cis-plastinum did not cause any change in hemoglobin, leukocyte count, platelet count and there was no correlation with the amount of infusion. 5) To see the side effect of hydration practiced with the infusion of Cis-platinum, the electrolytes, particularly the K level in the serum was measured. But the results did not show any change. 6) Judging from the results of this study mentioned above, ototoxicity caused by infusion of Cis-platinum can be prevented by sufficient hydration. Also the results might say that the appropriate method of infusion of Cis-platinum might be effective in the patients with head and neck cancer who had sensorineural hearing loss for whom the infusion of Cis-platinum has been absolutely cotraindicated.

• Journal of Life Science
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• v.18 no.4
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• pp.542-549
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• 2008

Cisplatin (cis-diamminedichloroplatinum II : CDDP) is the most widely used anticancer drug against a variety of human neoplasms. However, its clinical use is limited by the onset of severe side effects, including ototoxicity and nephrotoxicity. Even though a number of evidences in cytotoxic mechanism of cisplatin have been suggested, the role of pro-inflammatory cytokines in cisplatin cytotoxicity of auditory cells has not yet been demonstrated. Herein our data clearly demonstrated that cisplatin decreased the viability of HEI-OC1 auditory cells, which was inhibited by the addition of neutralizing $anti-TNF-{\alpha}$, $anti-IL-1{\beta}$ and anti-IL-6 antibodies. Consistently, Neutralization with antibodies against pro-inflammatory cytokines ameliorated the cell death and disarrangement of cochlea hair cell layers in the rat primary cochlear explants which were treated with cisplatin. Furthermore, exogeneous supplementation with free radical scavengers, including GSH and NAC, significantly prevented the cytotoxicity of cisplatin in the rat primary cochlea explants. We also observed that $TNF-{\alpha}$ was predominantly expressed in Deiters and Hensen's cells located in hair cell zone of cisplatin-treated cochlear explants. These findings suggest that pro-inflammatory cytokines, including $TNF-{\alpha}$, $IL-1{\beta}$ and IL-6, may play a pivotal role in the pathophysiology of hair cell damages caused by ototoxic drug cisplatin.

• Journal of Ginseng Research
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• v.45 no.1
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• pp.183-190
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• 2021

Background: The circadian rhythm is the internal clock that controls sleep-wake cycles, metabolism, cognition, and several processes in the body, and its disruption has been associated with aging. The differentiated embryo chondrocyte (Dec) gene is related to circadian rhythm. To our knowledge, there are no reports of the relationship between dec gene expression and KRG effect. Therefore, we treated Dec gene knockout (KO) aging mice with KRG to study anti-aging related effects and possible mechanisms. Methods: We evaluated KRG and expression of Dec genes in an ototoxicity model. Dec genes expression in livers of aging mice was further analyzed. Then, we assessed the effects of DEC KO on hearing function in mice by ABR. Finally, we performed DNA microarray to identify KRG-related gene expression changes in mouse liver and assessed the results using KEGG analysis. Results: KRG decreased the expression of Dec genes in ototoxicity model, which may contribute to its anti-aging efficacy. Moreover, KRG suppressed Dec genes expression in liver of wild type indicating inhibition of senescence. ABR test indicated that KRG improved auditory function in aging mouse, demonstrating KRG efficacy on aging related diseases. Conclusion: Finally, in KEGG analysis of 238 genes that were activated and 158 that were inhibited by KRG in DEC KO mice, activated genes were involved in proliferation signaling, mineral absorption, and PPAR signaling whereas the inhibited genes were involved in arachidonic acid metabolism and peroxisomes. Our data indicate that inhibition of senescence-related Dec genes may explain the anti-aging efficacy of KRG.

• Journal of Korean Neurosurgical Society
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• v.30 no.5
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• pp.638-641
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• 2001

Carboplatin intra-arterial chemotherapy(IAC) has an advantage of increased uptake during the first passage of the drugs through tumor capillaries. Although not common, this type of therapy is known to cause neurological complications, myelosuppression, and ototoxicity. However, the incidence of ocular toxicity is reported to be rare. Eleven of our patients with glioma(Grade II Astrocytoma : 3, Grade III Astrocytoma : 1, Grade IV Astrocytoma : 5, Gliofibroma : 1, Oligodendroglioma : 1) underwent IAC regimen with carboplatin($300mg/m^2$) which were administrated after blood-brain barrier disruption. Of there, 3 patients had ocular complications after supra-ophthalmic IAC injection of carboplatin but fully recovered following steroid therapy. Although our results from IAC seem to be favorable for these patients, we suggest that its complications, such as ocular toxicity, need to be carefully considered prior to treatment.