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评价二苯甲酮-3 对雄性 Sprague-Dawley 大鼠的抗雄激素和细胞毒性作用。

Evaluation of the anti-androgenic and cytotoxic effects of benzophenone-3 in male Sprague-Dawley rats.

机构信息

Department of Bio Health Science, College of Natural Science, Changwon National University, Changwon, Republic of Korea.

Nonclinical Research Center, Chemon Inc., Yongin, Republic of Korea.

出版信息

J Toxicol Environ Health A. 2024 Mar 18;87(6):266-273. doi: 10.1080/15287394.2023.2300785. Epub 2024 Jan 10.

Abstract

Benzophenone-3 (BP-3, 2-hydroxy-4-methoxybenzophenone, oxybenzone) is one of the most widely used types of benzophenone organic sunscreen. However, this compound is a potentially harmful toxicant. The aim of this study was 2-fold to: (1) utilize a Hershberger bioassay in castrated male Sprague-Dawley rats to investigate the anti-androgenic activities of BP-3, and (2) use a methyl tetrazolium assay to compare the toxicity between Leydig cells (TM3 cells) and mouse fibroblast (NIH-3T3) cell lines. In the Hershberger assay, rats were divided into 6 groups (each of  = 7): a vehicle control, negative control, positive control, PB-3 low (40 mg/kg), BP-3 intermediate (200 mg/kg), and BP-3 high (1000 mg/kg)-dose. The weight of the ventral prostate was significantly decreased at BP-3 doses of 200 or 1,000 mg/kg/day. In addition, the levator anibulbocavernosus muscle weights were also significantly reduced at BP-3 doses of 40, 200, or 1,000 mg/kg/day. In the MTT assay, the viability of NIH-3T3 mouse fibroblast cells was within the normal range. However, the TM3 mouse testis Leydig cell viability was significantly lowered in a concentration-dependent manner. Therefore, data indicate that BP-3 might exert anti-androgenic and cytotoxic effects in cells associated with the male reproductive system compared to normal non-reproductive cells. BP-3: benzophenone-3; CG: Cowper's gland; DMEM: Dulbecco's modified Eagle's medium; DMSO: dimethyl sulfoxide; GP: glans penis; LABC: levator anibulbocavernosus muscle; MTT: methyl tetrazolium; NC: negative control; PC: positive control; SV: seminal vesicle; TP: testosterone propionate; VC: vehicle control; VP: ventral prostate.

摘要

二苯甲酮-3(BP-3,2-羟基-4-甲氧基二苯甲酮,氧苯酮)是最广泛使用的苯甲酮有机防晒霜之一。然而,这种化合物是一种潜在的有害有毒物质。本研究的目的有两个方面:(1)利用去势雄性 Sprague-Dawley 大鼠的 Hershberger 生物测定法来研究 BP-3 的抗雄激素活性,(2)利用甲基噻唑基四唑测定法比较 Leydig 细胞(TM3 细胞)和小鼠成纤维细胞(NIH-3T3)细胞系之间的毒性。在 Hershberger 测定法中,将大鼠分为 6 组(每组=7):载体对照、阴性对照、阳性对照、PB-3 低(40mg/kg)、BP-3 中(200mg/kg)和 BP-3 高(1000mg/kg)剂量。BP-3 剂量为 200 或 1000mg/kg/天时,前列腺腹叶重量显著降低。此外,BP-3 剂量为 40、200 或 1000mg/kg/天时,肛提肌的重量也显著降低。在 MTT 测定法中,NIH-3T3 小鼠成纤维细胞的活力在正常范围内。然而,TM3 小鼠睾丸间质细胞的活力呈浓度依赖性显著降低。因此,数据表明,与正常非生殖细胞相比,BP-3 可能在与男性生殖系统相关的细胞中发挥抗雄激素和细胞毒性作用。BP-3:二苯甲酮-3;CG:库珀氏腺;DMEM:杜尔贝科改良 Eagle 培养基;DMSO:二甲基亚砜;GP:阴茎龟头;LABC:肛提肌;MTT:甲基噻唑基四唑;NC:阴性对照;PC:阳性对照;SV:精囊;TP:丙酸睾酮;VC:载体对照;VP:前列腺腹叶。

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