The small-molecule TNF-α inhibitor, UTL-5g, delays deaths and increases survival rates for mice treated with high doses of cisplatin.
The small-molecule TNF-α inhibitor, UTL-5g, delays deaths and increases survival rates for mice treated with high doses of cisplatin.
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小分子 TNF-α 抑制剂 UTL-5g 可以延迟接受高剂量顺铂治疗的小鼠的死亡并提高其存活率。
DOI：
10.1007/s00280-013-2236-4
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发表时间：
2013-09
影响因子：
3
通讯作者：
Valeriote, Fredrick
中科院分区：
文献类型：
--
作者：
Shaw, Jiajiu;Media, Joseph;Chen, Ben;Valeriote, Fredrick
UTL-5g 是一种新型小分子化学保护剂，可通过抑制 TNF-α 等因素降低顺铂引起的肝毒性、肾毒性和骨髓毒性。本研究的目的是探讨UTL-5g是否可以降低顺铂的总体急性毒性并增加小鼠对顺铂的耐受性。 BDF1 雌性小鼠在腹膜内注射前 30 分钟，通过口服强饲法以 60 mg/kg 的方式分别用 UTL-5g（悬浮于 Ora-Plus）进行治疗。第0天分别注射10、15和20 mg/kg的顺铂。从第1天开始，再次每天给小鼠注射相同剂量的UTL-5g，连续4天。监测存活率和体重。对于接受 150% 最大耐受剂量 (MTD) 顺铂 (15 mg/kg) 治疗的小鼠，UTL-5g 治疗提高了存活率并延迟了死亡时间。同样，在顺铂 MTD（20 mg/kg）的 200% 时，UTL-5g 治疗可提高存活率并延迟死亡时间。 UTL-5g的治疗对顺铂引起的体重减轻没有显着影响，表明体重对于UTL-5g针对顺铂的化学保护可能不够敏感。综上所述，UTL-5g延迟了高剂量顺铂治疗小鼠的死亡并提高了其存活率，表明UTL-5g能够降低顺铂的整体急性毒性并增加小鼠对顺铂的耐受性；这与之前报道的 UTL-5g 的特定化学保护作用一致。有必要进一步研究 UTL-5g 与顺铂的组合。
UTL-5g is a novel small-molecule chemoprotector that lowers hepatotoxicity, nephrotoxicity, and myelotoxicity induced by cisplatin through TNF-α inhibition among other factors. The objective of this study was to investigate whether UTL-5g can reduce the overall acute toxicity of cisplatin and increase cisplatin tolerability in mice. BDF1 female mice were treated individually with UTL-5g (suspended in Ora-Plus) by oral gavage at 60 mg/kg, 30 min before i.p. injection of cisplatin at 10, 15, and 20 mg/kg respectively on Day 0. Starting from Day 1, individual mice were again treated daily by the same dose of UTL-5g for 4 consecutive days. Survivals and bodyweights were monitored. UTL-5g treatment increased the survival rate and delayed the time to death for mice treated with 150% of the maximum tolerated dose (MTD) of cisplatin (15 mg/kg). Likewise, at 200% of the MTD of cisplatin (20 mg/kg), treatment of UTL-5g increased the survival rate and delayed the time to death. Treatment of UTL-5g did not have a significant effect on weight-loss induced by cisplatin indicating that bodyweight may not be a sensitive enough measure for chemoprotection of UTL-5g against cisplatin. In summary, UTL-5g delayed deaths and increased survival rates of mice treated by high doses of cisplatin indicating that UTL-5g is capable of reducing the overall acute toxicity of cisplatin and increased cisplatin tolerability in mice; this is in line with the specific chemoprotective effects of UTL-5g previously reported. Further investigation of UTL-5g in combination with cisplatin is warranted.
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影响因子：
7.2
作者：
Psotová, J;Chlopcíková, S;Simánek, V
通讯作者：
Simánek, V
影响因子：
2.9
作者：
CERSOSIMO, RJ
通讯作者：
CERSOSIMO, RJ
影响因子：
2.9
作者：
Leite, Elaine A.;Lana, Angela M. Q.;De Oliveira, Monica C.
通讯作者：
De Oliveira, Monica C.
DOI：
10.1073/pnas.92.19.8846
发表时间：
1995-09-12
影响因子：
11.1
作者：
LI, RB;BIANCHET, MA;AMZEL, LM
通讯作者：
AMZEL, LM
影响因子：
3
作者：
Korst, AEC;Gall, HE;vanderVijgh, WJF
通讯作者：
vanderVijgh, WJF