烟拉文

Nicaraven是一种新颖的化学合成的羟基自由基清除剂。

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研究领域 >> 癌症

在健康志愿者血小板中,在浓度范围为350μM或更高的尼加拉文中,二磷酸腺苷(ADP)诱导的最大聚集率被显着抑制。 1.75 mM的nicaraven显着抑制胶原蛋白诱导的最大聚集率[1]。

Nicaraven抑制肝脏脂质过氧化,改善肝脏和全身血流动力学和能量代谢,抑制肝脏酶释放,肝静脉血内皮素-1升高,组织学损伤和中性粒细胞浸润肝脏[1]。 Nicaraven增加骨髓和外周血中c-kit(+)干/祖细胞的数量,年龄匹配的非照射健康小鼠的恢复率约为60-90％。来自造血干/祖细胞的集落形成作为功能指标的效力完全受到nicaraven治疗的保护[2]。尼卡拉文的给药显着增加了数量,改善了集落形成能力,并减少了造血干/祖细胞的DNA损伤。与接受安慰剂的小鼠相比,给予尼卡拉的小鼠的尿氧水平8-氧代-2'-脱氧鸟苷(DNA氧化的标志物)显着降低。尼卡拉文的给药显着降低了小鼠血浆中炎性细胞因子IL-6和TNF-α的水平[3]。

小鼠：为了研究尼卡拉文对造血干/祖细胞辐射损伤的保护作用及相关机制，12只小鼠每天接受1Gyγ射线连续5天（总共5Gy），然后每次暴露后不久，分别给予尼卡拉通（100mg / kg /天，Nicaraven组; n = 6）或仅盐水（安慰剂组; n = 6）腹膜内注射。在最后一次暴露后2天处死小鼠，收集尿液，血液和骨髓细胞样品并用于以下实验[3]。

[1]. Komiya T, et al. A novel free radical scavenger, nicaraven, inhibits human platelet aggregation in vitro. Clin Neuropharmacol. 1999 Jan-Feb;22(1):11-4.

[2]. Yokota R, et al. A novel hydroxyl radical scavenger, nicaraven, protects the liver from warm ischemia and reperfusion injury. Surgery. 2000 Jun;127(6):661-9.

[3]. Ali H, et al. The potential benefits of nicaraven to protect against radiation-induced injury in hematopoietic stem/progenitor cells with relative low dose exposures.

[4]. Nicaraven attenuates radiation-induced injury in hematopoietic stem/progenitor cells in mice. PLoS One. 2013;8(3):e60023.

磺丁基-β-环糊精钠盐 | 环孢霉素A | 2-(3,6-二乙酰氧基-2,7-二氯-9H-氧杂蒽-9-基)苯甲酸 | 1-甲基-4-苯基-1,2,3,6-四氢吡啶盐酸盐 | GW4869 | 乙莫克舍 | (2R,2'R,3R,3'R,4S,4'S,5R,5'R,6S,6'S)-6,6'-硫代双(4-(4-(3-氟苯基)-1H-1,-1H-1,2,3-三唑-1-基)-2-(羟甲基)四氢-2H-吡喃-3,5-二醇) | Mitoquinone甲磺酸盐 | GSK2795039 | CBIC2 | BAPTA-AM | AP20187 | GKT137831 | D-(-)-荧光素 | 单响尾蛇毒蛋白

MOLECULAR FORMULA :

C15-H16-N4-O2

MOLECULAR WEIGHT :

284.35

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

840 mg/kg

TOXIC EFFECTS :

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

REFERENCE :

YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 23(Suppl 1),S9,1995

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

590 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea Skin and Appendages - hair

REFERENCE :

YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 23(Suppl 1),S5,1995

TYPE OF TEST :

LD - Lethal dose

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

>1 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

EPXXDW European Patent Application. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) Volume(issue)/page/year: #0029602

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

1500 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold

REFERENCE :

YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 23(Suppl 1),S13,1995 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

22680 mg/kg/4W-I

TOXIC EFFECTS :

Endocrine - changes in adrenal weight Blood - normocytic anemia Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :

YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 23(Suppl 1),S21,1995

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

49140 mg/kg/26W-I

TOXIC EFFECTS :

Endocrine - changes in spleen weight Blood - normocytic anemia Blood - other changes

REFERENCE :

YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 23(Suppl 1),S69,1995

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

9450 mg/kg/5W-I

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - lacrimation Sense Organs and Special Senses (Eye) - effect, not otherwise specified

REFERENCE :

YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 23(Suppl 1),S41,1995

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

26400 mg/kg/26W-I

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - ptosis Sense Organs and Special Senses (Eye) - effect, not otherwise specified

REFERENCE :

YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 23(Suppl 1),S103,1995 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

12 gm/kg

SEX/DURATION :

male 60 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands

REFERENCE :

YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 23(Suppl 1),S155,1995