非普拉宗

非普拉松(DA2370；Prenazone)是苯基丁酮(HY-B0230)的类似物,是一种非甾体抗炎剂,具有镇痛和解热作用。Feprazone通过抑制环氧合酶(COX)-2的活性而起作用。Feprazne通过减少线粒体活性氧(ROS)的产生来改善游离脂肪酸(FFA)诱导的氧化应激。Feprazone可降低MMP-2和MMP-9的表达。此外,Feprazene可抑制T3-L1细胞分化过程中的脂肪生成,增加脂肪分解。非普拉松还可用于研究动脉粥样硬化和肥胖[1][2][3]。

研究领域 >> 炎症/免疫

信号通路 >> 免疫及炎症 >> COX

信号通路 >> 代谢酶/蛋白酶 >> MMP

COX, Reactive oxygen species, MMP[1]

Feprazone(2.5-10μM；48 h)挽救FFAs刺激的人主动脉内皮细胞(HAEC)的细胞活力[1]。Feprazone(5,10μM；24 h)分别在5和10μM时将HAEC中的ROS生成降低至2.4倍和1.6倍,而300μM FFA将ROS生成增加3.4倍；还降低细胞因子CCL5、IL-6和IL-8以及MMP-2和MMP-9的mRNA表达和分泌[1]。Feprazone(5,10μM；6 h)降低TLR4和MyD88的活性,并降低p65的磷酸化和随后的NF-κB的活化[1]。Feprazone(30和60μM；7天)抑制分化的3个T3-L1细胞的脂肪生成；在3T3-L1脂肪生成过程中降低甘油三酯含量并增加脂肪分解[3]。细胞活力测定[1]细胞系：HAEC(用300μM FFA刺激)浓度：2.5、5和10μM孵育时间：48小时结果：在5和10µM时,细胞活力分别恢复到基线的81%和93%,而FFA将细胞活力降低到基线的63%。RT-PCR[1]细胞系：HAEC(用300μM FFA刺激)浓度：5和10μM孵育时间：24小时结果：以剂量依赖性方式降低细胞因子CCL5、IL-6和IL-8的mRNA表达和分泌。剂量依赖性地将VCAM-1和ICAM-1的表达分别降低到1.7倍和1.8倍,而FFA分别增加到2.8倍和3.4倍。Western Blot分析[1]细胞系：HAEC(用300μM FFA刺激)浓度：5和10μM孵育时间：6小时结果：降低TLR4和MyD88的表达,以及降低p65的磷酸化和随后的NF-κB的活化。

显著抑制HFD小鼠的脂肪细胞大小、内脏脂肪细胞组织重量和平均体重[3]。动物模型：雄性C57BL/6 N小鼠[高脂饮食(HFD)诱导的肥胖模型][3]剂量：75 mg/kg给药：(研究中未描述)结果：对照组、HFD组和HFD+Feprazone组小鼠的内脏脂肪细胞组织重量分别为0.38、3.51和2.37 g。对照组、HFD组和HFD+Feprazone组小鼠的平均体重分别为29.6、41.3和34.1 g。

MOLECULAR FORMULA :

C20-H20-N2-O2

MOLECULAR WEIGHT :

320.42

WISWESSER LINE NOTATION :

T5VNNV EHJ BR& CR& E2UY1&1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1343 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

REFERENCE :

IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 10,133,1979

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

362 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

REFERENCE :

IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 10,133,1979

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

386 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

YHTPAD Yaoxue Tongbao. Bulletin of Pharmacology. (China International Book Trading Corp., POB 2820, Beijing, Peop. Rep. China) V.13-23, 1978-88. For publisher information, see ZYZAEU. Volume(issue)/page/year: 20,267,1985

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1067 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 22,196,1972

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

270 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

REFERENCE :

IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 10,133,1979

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

374 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

REFERENCE :

IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 10,133,1979

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

180 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 22,196,1972

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

>2 gm/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Gastrointestinal - ulceration or bleeding from stomach

REFERENCE :

YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 33,233,1982 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

18 gm/kg/30D-C

TOXIC EFFECTS :

Gastrointestinal - ulceration or bleeding from stomach Liver - changes in liver weight Related to Chronic Data - death

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 64,255,1982

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

98820 mg/kg/26W-C

TOXIC EFFECTS :

Liver - changes in liver weight Kidney, Ureter, Bladder - changes in bladder weight Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 64,255,1982

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

6300 mg/kg/21D-I

TOXIC EFFECTS :

Liver - changes in liver weight Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Related to Chronic Data - death

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 22,226,1972

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

16800 mg/kg/14W-I

TOXIC EFFECTS :

Cardiac - changes in heart weight Liver - changes in liver weight Kidney, Ureter, Bladder - other changes in urine composition

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 22,216,1972

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

32400 mg/kg/30D-C

TOXIC EFFECTS :

Blood - normocytic anemia Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Related to Chronic Data - death

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 64,255,1982

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

54750 mg/kg/1Y-C

TOXIC EFFECTS :

Blood - normocytic anemia Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Liver - changes in liver weight

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 64,255,1982 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1320 mg/kg

SEX/DURATION :

female 7-17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - delayed effects

REFERENCE :

IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 10,149,1979

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

2640 mg/kg

SEX/DURATION :

female 7-17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :

IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 10,149,1979

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

180 mg/kg

SEX/DURATION :

female 17-22 day(s) after conception

TOXIC EFFECTS :

Reproductive - Maternal Effects - parturition

REFERENCE :

IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 10,164,1979

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1620 mg/kg

SEX/DURATION :

female 17-22 day(s) after conception lactating female 21 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :

IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 10,164,1979

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1560 mg/kg

SEX/DURATION :

female 6-18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :

IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 10,149,1979

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

3120 mg/kg

SEX/DURATION :

female 6-18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - abortion

REFERENCE :

IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 10,149,1979