氯唑西林

氯唑西林是一种口服活性抗菌剂和β-内酰胺酶抑制剂,IC50为0.04µM。氯唑西林可以通过抑制MAPK、NF-κB和NLRP3相关蛋白的激活来抑制金黄色葡萄球菌诱导的炎症反应[1][2][3]。

研究领域 >> 癌症

研究领域 >> 感染

研究领域 >> 炎症/免疫

信号通路 >> 抗感染 >> 细菌

IC50: 0.04 µM (β-lactamase from wild type A.caviae), 0.3 µM (β-lactamase from mutant A.caviae)[3].

氯唑西林(0-2048µg/mL；20-24小时)对金黄色葡萄球菌8325-4和DU1090具有良好的抗菌活性,MIC值均为0.125µg/mL[1]。氯唑西林(0.015625μg/mL；6小时)在体外抑制Hlα的溶血活性,这种抑制作用不仅在与TZ和TZ联合使用时更为明显,而且通过抑制MAPK、NF-κB和NLRP3相关蛋白的激活来抑制炎症反应[1]。细胞活力测定[1]细胞系：金黄色葡萄球菌8325-4,金黄色葡萄杆菌DU1090(一种Hlα缺失菌株)浓度：0-2048µg/mL培养时间：20-24小时结果：抑制金黄色葡萄菌8325-2和DU1090,MIC值均为0.125µg/mL。Western Blot分析[1]细胞系：金黄色葡萄球菌8325-4浓度：0.015625μg/mL(与噻唑嗪(TZ,0.25μg/mL)和四环素(TC,0.03125μg/mL)联合使用)。孵育时间：6h结果：抑制Hlα的表达,与TZ和TC联合使用时抑制作用更明显。Western Blot分析[1]细胞系：RAW264.7细胞(暴露于金黄色葡萄球菌8325-4/DU1090或纯Hlα)浓度：0.015625μ。孵育时间：6小时结果：与TC和TZ联合使用时,抑制MAPK、NF-κB和NLRP3相关蛋白的激活,从而抑制炎症反应。

氯唑西林(1.6125 mg/kg；皮下注射；72小时间隔12小时)与噻嗪嗪和四环素联合使用时,可在体内保护小鼠免受金黄色葡萄球菌腹膜炎[1]。氯唑西林(7.5 mg/per；i.p.；从第3天起每天两次,持续3天)与抗IL-15抗体结合时,会发生较轻的滑膜炎,并减少骨侵蚀[3]。动物模型：雌性BALB/c小鼠(6周龄；腹膜炎模型)[1]。剂量：1.6125mg/kg(与TC(3.125mg/kg)和TZ(25mg/千克)联合用药)：皮下注射；结果：小鼠肺组织中炎性细胞浸润程度降低,肺泡结构趋于正常。显著减少脾脏和肝组织的病理变化,并减少腹腔内金黄色葡萄球菌的CFU计数。动物模型：雌性野生型C57BL/6小鼠(8周龄；全身性金黄色葡萄球菌诱导的关节炎模型)剂量：7.5 mg/per(与25µg/per抗IL-15抗体联合使用)给药：腹腔注射；从第3天(细菌接种后)开始每天两次,第6天停止。结果：与抗IL-15抗体联合使用时,显示出减少严重滑膜炎和骨侵蚀的活性。

[1]. Zhou H, et al. The combination of cloxacillin, thioridazine and tetracycline protects mice against Staphylococcus aureus peritonitis by inhibiting α-Hemolysin-induced MAPK/NF-κB/NLRP3 activation. Int J Biol Macromol. 2022 Feb 15;198:1-10.

[2]. Bergmann B, et al. Antibiotics with Interleukin-15 Inhibition Reduce Joint Inflammation and Bone Erosions but Not Cartilage Destruction in Staphylococcus aureus-Induced Arthritis. Infect Immun. 2018 Apr 23;86(5):e00960-17.

[3]. Lupiola-Gómez PA, et al. Group 1 beta-lactamases of Aeromonas caviae and their resistance to beta-lactam antibiotics. Can J Microbiol. 2003 Mar;49(3):207-15.

MOLECULAR FORMULA :

C19-H18-Cl-N3-O5-S

MOLECULAR WEIGHT :

435.91

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

429 mg/kg/10D-I

TOXIC EFFECTS :

Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Kidney, Ureter, Bladder - interstitial nephritis Blood - eosinophilia

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

200 mg/kg/5D-I

TOXIC EFFECTS :

Liver - jaundice, other or unclassified Liver - liver function tests impaired

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - child

DOSE/DURATION :

5600 mg/kg/5W-I

TOXIC EFFECTS :

Kidney, Ureter, Bladder - interstitial nephritis Nutritional and Gross Metabolic - body temperature increase

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intracerebral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

8100 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

7 gm/kg/4W-I

TOXIC EFFECTS :

Lungs, Thorax, or Respiration - changes in lung weight Liver - changes in liver weight Endocrine - hypoglycemia

MUTATION DATA

TYPE OF TEST :

Sister chromatid exchange

TEST SYSTEM :

Human Lymphocyte

DOSE/DURATION :

400 mg/L

REFERENCE :

BSIBAC Bolletino della Societe Italiana di Biologia Sperimentale. (Casa Editrice Idelson, Via A. de Gasperi, 55, 80133 Naples, Italy) V.2- 1927- Volume(issue)/page/year: 60,2143,1984