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Je‑Oh Lim,Je‑Won Ko,Tae‑Yang Jung,Woong‑Il Kim,So‑Won Pak,In‑Sik Shin,Won‑Kee Yun,Hyoung‑Chin Kim,Jeong‑Doo Heo,Jong‑Choon Kim 대한독성 유전단백체 학회 2020 Molecular & cellular toxicology Vol.16 No.3
Background Silica dioxide nanoparticles (SiONPs) have been used for various medical applications, including therapeutics and imaging, and the use of SiONPs has increased gradually over the years. However, despite an increase in the use of SiONPs, not much is known about mechanism of action of SiONPs and their pulmonary toxicity. Objective The present study investigated the pulmonary toxicity of SiONPs and explored the underlying mechanism of action, primarily focusing on thioredoxin-interacting protein (TXNIP)/NOD-like receptor pyrin domain-containing 3 (NLRP3) in SiONPs-treated mice. We investigated the toxic effects of SiONPs in the lung of BALB/c mice administered 5, 10, and 20 mg/kg SiONPs for 3 days. Results Exposure to SiONPs markedly increased inflammatory cell counts, including those of neutrophils and macrophages, and levels of inflammatory mediators, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in a dose-dependent manner in the bronchoalveolar lavage fluid. Moreover, the inflammation was verified upon histopathological analysis. In addition, exposure to SiONPs increased the expression of TXNIP in a dose-dependent manner and, in turn, upregulated NLRP3 inflammasome proteins, which subsequently induced IL-1β production. Conclusion Collectively, exposure to SiONPs induced inflammation in the lungs of mice, which resulted in the activation of IL-1β production via the TXNIP-NLRP3 axis. Our results provide useful information on the pulmonary toxicity induced by SiONPs and provide insights into the underlying mechanism of action.
만성 C형 간염 환자에서 페그인터페론 알파2a와 리바비린 병합 치료중 발생한 벨마비 1예
김일환,장제혁,유충헌,최규남,고정해,김윤정,서광원,김지현,박성재,박은택,이연재,이상혁,설상영 인제대학교 2008 仁濟醫學 Vol.29 No.-
페그인터페론과 리바비린 병합요법은 만성 C형 간염의 일차 치료법이다. 저자들은 만성 C형 간염 환자에서 페그인터페론 과 리바비린 병합 요법 중에 발생한 벨마비 1예를 경험하였기에 문헌고찰과 함께 보고하는 바이다. 환자는 5년 전부터 만성 C형 간염을 앓아온 48세 남자이며, PEG-IFN α-2a 135μgm 피하주사 주1회와 하루 1200㎎의 리바비린을 투여하였다. 치료시작 후 9개월째 환자는 오른쪽 안면의 근력약화를 호소하였으며 벨마비로 진단되었다. 페그인터페론과 리바비린 병합요법을 지속하면서 관찰하였다. 환자의 벨마비는 페그인터페론 치료를 중단하지 않았음에도 3개월후 증상이 회복되고 이후 벨마비 재발 없이 현재 경과관찰 중이다. 만성 C형 간염에서 페그인터페론과 리바비린 병합 요법시 벨마비의 발생 가능성을 염두에 두어야 하겠다. A Case of Bell's Palsy Associated with Combination Therapy of Pegylated Interferon Alfa-2a (PEG-IFN) and Ribavirin for Chronic Hepatitis C Virus Infection Pegylated interferon alfa(PEG-IFN α) and ribavirin therapy is the first line treatment for chronic hepatitis C. Mild complications of the therapy are common, but more serious complications are rare. We report here a case of Bell's palsy that occurred in a patient with chronic hepatitis C virus infection during combination therapy of PEG-IFN α-2a and ribavirin. The patient was 49-year-old man with chronic hepatitis C (genotype 1b) for 8 years. He had compensated liver cirrhosis with splenomegaly. Therapy with PEG-IFN α- 2a 135mcg/week and ribavirin 1200mg/day was initiated. After 9 months of the therapy, the patient showed a loss of muscular tone on the right side of his face. A diagnosis of Bell's palsy was made. The Bell's palsy resolved over 3 months despite continuation of the combination therapy.
Ko, Je-Won,Shin, Na-Rae,Jung, Tae-Yang,Shin, In-Sik,Moon, Changjong,Kim, Sung-Ho,Lee, In-Chul,Kim, Sung-Hwan,Yun, Won-Kee,Kim, Hyoung-Chin,Kim, Jong-Choon Elsevier 2019 Food and chemical toxicology Vol.129 No.-
<P><B>Abstract</B></P> <P>This study investigated the protective effects of melatonin (MT) against cisplatin (CP)-induced acute kidney injury in rats as well as its possible mechanism of action associated with anti-aging protein Klotho. The following four experimental groups were evaluated: vehicle control, CP (7 mg/kg), CP&MT20 (20 mg/kg/day), and CP&MT40 (40 mg/kg/day). The concomitant administration of MT significantly ameliorated CP-induced acute kidney injury in rats, as evidenced by increased kidney weight, increased serum levels of blood urea nitrogen and creatinine, and increased incidence of histopathological alterations with renal tubular cell apoptosis. In addition, MT treatment protected kidney tissue against oxidative damages and significantly upregulated the expression level of Klotho decreased by CP treatment, resulting in reduced phosphorylation of protein kinase B (AKT) and forkhead box O (FOXO) as well as reduced expression levels of B-cell lymphoma 2-associated X protein (Bax) and caspase-3. MT not only partially regulated oxidative stress via AKT/FOXO signaling, but also reduced apoptosis caused by CP by inhibiting the Bax/caspase-3 pathway. Our results indicated that MT could prevent acute kidney injury induced by CP in rats, presumably through upregulating the expression of Klotho, resulting in elevated anti-oxidant and anti-apoptotic properties.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Melatonin (MT) attenuated acute kidney injury induced by cisplatin (CP). </LI> <LI> MT upregulated the expression level of Klotho decreased by CP treatment. </LI> <LI> Upregulated Klotho attenuated oxidative stress and apoptosis induced by CP. </LI> </UL> </P>