An Open Label, Single-Arm, Phase I Exploratory Trial to Assess the Safety and Preliminary Efficacy of mFOLFIRINOX with Hydroxychloroquine and Chlorphenesin carbamate in Patient with in Inoperable Locally Advanced or Metastatic Pancreatic Cancer

开始日期2021-12-21

申办/合作机构

Asan Medical Center

100 项与氯苯甘醚相关的临床结果

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100 项与氯苯甘醚相关的转化医学

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100 项与氯苯甘醚相关的专利（医药）

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172

项与氯苯甘醚相关的文献（医药）

2024-11-01·Biological Trace Element Research

Boric Acid and Borax Protect Human Lymphocytes from Oxidative Stress and Genotoxicity Induced by 3-Monochloropropane-1,2-diol

Article

作者: Yıldız, Edanur ; Saracoglu, Muhammed Melik ; Baba, Cem ; Arslan, Mehmet Enes ; Mardinoglu, Adil ; Turkez, Hasan ; Tozlu, Ozlem Ozdemir ; Tatar, Abdulgani

Abstract3-chloro-1,2-propanediol (3-MCPD) is a member of the group of pollutants known as chloropropanols and is considered a genotoxic carcinogen. Due to the occurrence of 3-MCPD, which cannot be avoided in multiplexed food processes, it is necessary to explore novel agents to reduce or prevent the toxicity of 3-MCPD. Many recent studies on boron compounds reveal their superior biological roles such as antioxidant, anticancer, and antigenotoxic properties. In the current investigation, we have evaluated in vitro cytotoxic, oxidative, and genotoxic damage potential of 3-MCPD on human whole blood cultures and the alleviating effect of boric acid (BA) and borax (BX) for 72 h. In our in vitro experiments, we have treated blood cells with BA and BX (2.5, 5, and 10 mg/L) and 3-MCPD (at IC50 of 11.12 mg/l) for 72 h to determine the cytotoxic damage potential by using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and lactate dehydrogenase (LDH) release assays. Oxidative damage was assessed using total antioxidant capacity (TAC) and malondialdehyde (MDA) levels. Genotoxicity evaluations were performed using chromosome aberrations (CAs) and 8-hydroxy deoxyguanosine (8-OHdG) assays. The result of our experiments showed that the 3-MCPD compound induced cytotoxicity, oxidative stress, and genotoxicity in a clear concentration-dependent manner. BA and BX reduced cytotoxicity, oxidative stress, and genotoxicity induced by 3-MCPD. In conclusion, BA and BX are safe and non-genotoxic under the in vitro conditions and can alleviate cytotoxic, oxidative, and genetic damage induced by 3-MCPD in the human blood cells. Our findings suggest that dietary boron supplements may offer a novel strategy for mitigating hematotoxicity induced by xenobiotics, including 3-MCPD.

2024-09-01·Reproductive Toxicology

3-chloro-1,2-propanediol induces oxidative stress and promotes testicular damage and infertility in rats through CYP2C9

Article

作者: Li, Xue ; Zhang, Hong ; Xue, Boxin ; Gao, Chuchu ; Fu, Kai

3-chloro-1,2-propanediol (3-MCPD) is a newly discovered food process pollutant with nephrotoxicity. And the mechanism by which 3-MCPD affects male spermatogenesis has not been fully studied. Cell viability, blood-testis barrier (BTB) related protein, progesterone content, reactive oxygen species (ROS) generation, and cell apoptosis were determined by a CCK8 assay, western blot, ELISA, flow cytometry, and TUNEL staining, respectively. Wistar rats were divided into three groups: low-dose 3-MCPD, high-dose 3-MCPD, and control. Sperm parameters, hormonal levels, and biomarkers of oxidative stress in the testis and epididymis were detected by ELISA. Multiple molecular experiments including molecular docking and western blot were used to elucidate the underlying mechanisms. 3-MCPD affects testicular cell activity, and promotes ROS production and apoptosis. Disrupting the integrity of BTB in the body, downregulating sex hormones and sperm quality, and promoting apoptosis. 3-MCPD may function through CYP2C9. This study preliminarily explores the mechanism by which 3-MCPD affects spermatogenesis. It was found that 3-MCPD destroys the structure and function of BTB and damages the testicular function of male mice, thus affecting the process of spermatogenesis via CYP2C9.

2024-08-01·Toxicology in Vitro

Antifungal climbazole alters androgenic pathways in mammalian cells

Article

作者: Gaté, Laurent ; Lorcin, Mylène ; Perceau, Marie ; Ndiaye, Dieynaba ; Denis, Flavien

Among antifungal agents used in pharmaceuticals and personal care products, the synthetic azole climbazole (CBZ; 1-(4-Chlorophenoxy)-1-(imidazol-1-yl)-3,3-dimethylbutan-2-one) acts on the fungus Malassezia. Despite concerns surrounding its effects on health, based on alterations to reproduction and steroidogenesis found in fish, little is known about its mechanism of action as an endocrine disrupting chemical (EDC) in mammalian cells. In this study, using OECD test guidelines, we investigated the effects of CBZ (i) in H295R cells, on the production of estradiol and testosterone, as well as intermediate metabolites in steroidogenesis pathway, and (ii) in HeLa9903 and AR-EcoScreen cell lines, on the transactivation of estrogen and androgen receptors. Our results are the first evidence in H295R cells, that CBZ treatment (from 0.3 μM) decreased secreted levels of testosterone and estradiol. This was associated with reduced 17α-hydroxypregnenolone and 17α-hydroxyprogesterone levels. The altered levels of these metabolites were associated with a decrease in cytochrome P450 17α-hydroxylase/17,20-lyase (Cyp17A1) activity without any effect on its protein level. CBZ was also found to exert antagonistic effects toward androgen and estrogen α receptors. These results give insights into the toxicological mechanism of action of CBZ. Many azoles share structural similarities; therefore, caution should be adopted due to their potential toxicity.

100 项与氯苯甘醚相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00770	氯苯甘醚	D01AE07	DB14656

研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
颈臂综合征	日本	Taisho Pharmaceutical Co., Ltd.	1986-06-01
腰痛	日本	Taisho Pharmaceutical Co., Ltd.	1979-03-13
骨质疏松症	日本	Taisho Pharmaceutical Co., Ltd.	1979-03-13
脊椎滑脱症	日本	Taisho Pharmaceutical Co., Ltd.	1979-03-13