萘普生

Naproxen是COX-1 和 COX-2 的抑制剂,在细胞试验中 IC50 值分别为8.72 和5.15 μM.

信号通路 >> 自噬 >> 自噬

研究领域 >> 炎症/免疫

COX-2:5.65 μM (IC50)

COX-1:9.55 μM (IC50)

Naproxen etemesil是一种亲脂性,非酸性,无活性的萘普生前药,一旦被吸收就会水解成药理活性的萘普生。萘普生是一种众所周知的非甾体抗炎药。 Naproxen在完整细胞中大约是COX-1和COX-2的等效抑制剂,IC50分别为2.2μg/ mL和1.3μg/ mL [1]。

萘普生在博来霉素诱导的肺纤维化小鼠模型中发挥抗炎和抗纤维化作用。萘普生还可下调TGF-β水平和Smad3/4复合物的形成[2]。萘普生可以抑制疼痛,发热和PGE2的时间过程,具有相似的效力(IC50 =27,40,13μM)[3]。

将BAEC与萘普生（0.1ng / mL至1mg / mL）孵育30分钟。然后加入花生四烯酸（30μM），并将细胞在37℃下再温育15分钟。然后除去培养基，放射免疫测定用于测量6-酮-PGF，a，PGE2，血栓素B2或PGF2a的形成[1]。

大鼠[3]为了测量骆驼素在单关节炎的卡拉胶诱导模型中的镇痛作用，将雄性Sprague-Dawley大鼠（n = 48,217±28 g）随机分成4组，每组12只，通过内部开发的计算机程序，盲目表现行为实验。为了通过炎症诱导痛觉过敏，1B组，1C组和1D组中的动物在异氟烷麻醉下（时间= -1h）在左后肢接受40μL关节内注射含有7.5mg / mL角叉菜胶的盐水溶液。 1A组动物不接受注射。 1小时后（时间= 0），组1A，1B，1C和1D中的动物分别在0,0,7.5和30μmol/ kg的盐水中接受口服剂量的萘普生。测量的剂量和时间点是根据预测在实验时间跨度内测量完整浓度 - 效应关系的模拟来选择的[3]。将小鼠[2]博来霉素（0.05IU）气管内滴注至C57BL / 6小鼠，然后用载体JNJ7777120（40mg / kg b.wt。），萘普生（21mg / kg b）的微渗透泵处理。 wt。），或两者的组合。评估气道对通气的抵抗力，肺硬度指数，并对肺标本进行炎症，氧化应激和纤维化标志物处理[2]。

[1]. Mitchell JA, et al. Selectivity of nonsteroidal antiinflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11693-7.

[2]. Rosa AC, et al. Prevention of bleomycin-induced lung inflammation and fibrosis in mice by naproxen and JNJ7777120 treatment. J Pharmacol Exp Ther. 2014 Nov;351(2):308-16.

[3]. Krekels EH, et al. Pharmacokinetic-pharmacodynamic modeling of the inhibitory effects of naproxen on the time-courses of inflammatory pain, fever, and the ex vivo synthesis of TXB2 and PGE2 in rats.

对乙酰氨基苯酚 | 阿司匹林 | 非洲豆蔻醇 | 人参皂苷Rg3 | 人参皂苷CK | 黄腐酚 | 布洛芬 | 双氯芬酸 | NS-398(COX-2抑制剂) | 美洛昔康 | 氟芬那酸 | 表儿茶素(EC) | 水杨酸 | 酮洛芬 | 儿茶精； 儿茶素； (2R,3S)-2-(3,4-二羟基苯基)-3,4-二氢-2H-苯并吡喃-3,5,7-三醇

MOLECULAR FORMULA :

C14-H14-O3

MOLECULAR WEIGHT :

230.28

WISWESSER LINE NOTATION :

L66J CY1&VQ HO1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

315 mg/kg/3W-I

TOXIC EFFECTS :

Behavioral - excitement Gastrointestinal - hypermotility, diarrhea Gastrointestinal - nausea or vomiting

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

3429 mg/kg/35W-I

TOXIC EFFECTS :

Vascular - BP elevation not characterized in autonomic section Lungs, Thorax, or Respiration - cyanosis

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

126 mg/kg/3W-I

TOXIC EFFECTS :

Lungs, Thorax, or Respiration - fibrosis, focal (pneumoconiosis) Lungs, Thorax, or Respiration - dyspnea Blood - eosinophilia

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - child

DOSE/DURATION :

2250 mg/kg/26W-I

TOXIC EFFECTS :

Skin and Appendages - dermatitis, other (after systemic exposure)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

900 mg/kg/9W-I

TOXIC EFFECTS :

Skin and Appendages - photosensitivity (after systemic exposure)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

40 mg/kg/2D-I

TOXIC EFFECTS :

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

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

70 mg/kg/W-I

TOXIC EFFECTS :

Liver - jaundice, cholestatic

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human

DOSE/DURATION :

50 mg/kg/7D-I

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Gastrointestinal - hypermotility, diarrhea Gastrointestinal - other changes

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

248 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

354 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

928 mg/kg

TOXIC EFFECTS :

Lungs, Thorax, or Respiration - dyspnea Nutritional and Gross Metabolic - body temperature decrease

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

360 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

500 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

475 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

435 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - excitement

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1234 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

>1 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

1 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

665 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - hamster

DOSE/DURATION :

1400 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Rodent - hamster

DOSE/DURATION :

4110 mg/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 :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

20 mg/kg/4D-I

TOXIC EFFECTS :

Gastrointestinal - ulceration or bleeding from stomach

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

970 mg/kg/17D-I

TOXIC EFFECTS :

Gastrointestinal - ulceration or bleeding from small intestine Blood - other changes

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

20 mg/kg

SEX/DURATION :

female 30 week(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - respiratory system Reproductive - Specific Developmental Abnormalities - gastrointestinal system Reproductive - Specific Developmental Abnormalities - other developmental abnormalities

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

20 mg/kg

SEX/DURATION :

female 30 week(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - Apgar score (human only) Reproductive - Effects on Newborn - other neonatal measures or effects Reproductive - Effects on Newborn - biochemical and metabolic

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

120 mg/kg

SEX/DURATION :

female 28 week(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system Reproductive - Specific Developmental Abnormalities - respiratory system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

6 mg/kg

SEX/DURATION :

female 13 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

6 mg/kg

SEX/DURATION :

female 13 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :

Sister chromatid exchange

MUTATION DATA

TEST SYSTEM :

Rodent - mouse

DOSE/DURATION :

270 mg/kg

REFERENCE :

MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 393,123,1997 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X6164 No. of Facilities: 16 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 444 (estimated) No. of Female Employees: 260 (estimated)