Legal Performance-enhancing Drugs Alter Course and Treatment of Rhabdomyolysis-induced Acute Kidney Injury.
Legal Performance-enhancing Drugs Alter Course and Treatment of Rhabdomyolysis-induced Acute Kidney Injury.
复制标题
法律表现增强药物改变横纹肌溶解引起的急性肾损伤的病程和治疗。
DOI：
10.1093/milmed/usad142
复制
发表时间：
2023
影响因子：
1.2
通讯作者：
Hutchens,MichaelP
中科院分区：
文献类型：
--
作者：
Hebert,JessicaF;Eiwaz,MahabaB;Nickerson,MeganN;Munhall,AdamC;Pai,AkashA;Groat,Tahnee;Andeen,NicoleK;Hutchens,MichaelP
横纹肌溶解所致的急性肾损伤(RIAKI)可中断体能训练，增加受伤士兵的死亡率。服役人员广泛使用合法的提高成绩的药物咖啡因和布洛芬，它们可能会导致肾脏损伤。咖啡因或布洛芬是否影响RIAKI尚不清楚。西司他丁治疗最近被确定为预防损伤时RIAKI的实验性治疗方法。为了确定RIAKI治疗中潜在的相互作用因素，我们检验了咖啡因和布洛芬恶化RIAKI并干扰治疗的假设。材料与方法采用小鼠肌肉注射甘油诱发RIAKI模型。同时，小鼠接受咖啡因(3 mg/kg)、布洛芬(10 mg/kg)或赋形剂。第二组在咖啡因或布洛芬的基础上进行容量复苏(血浆Lyte，20 毫升/公斤)。在第三个队列中，西司他丁(200 mg/kg)与药物和甘油同时服用。24 后测定肾小球滤过率、血尿素氮、尿量、肾脏病理和肾脏损伤分子1的免疫荧光。结果咖啡因不加重RIAKI；尽管咖啡因使血尿素氮略有增加，但赋形剂治疗组、咖啡因治疗组和咖啡因 + 血浆赖特治疗组小鼠的24小时肾小球滤过率、尿蛋白排泄率和肾脏组织病理学相似。布洛芬给药后RIAKI显著恶化(对照组GFR 14.3 ± 19.5vs 577.4 ± 454.6 ·L/ /100 g，布洛芬治疗组UOP0.5 ± 0.4vs.2.7 ± 1.7min/24 ，布洛芬治疗组BUN 264 ± 201vs.66 ± 21 mg/dL，P <； .05)；血浆赖特治疗不能逆转这种作用。西司他丁与或不与血浆Lyte一起使用并不能逆转布洛芬在RIAKI中的有害作用。结论咖啡因不会加重RIAKI。广泛使用的提高成绩的药物布洛芬极大地恶化了小鼠的RIAKI。标准或实验性的RIAKI治疗，包括在标准复苏的基础上加用西司他丁，对布洛芬加重RIAKI的小鼠无效。这些发现可能对目前的RIAKI治疗和新疗法的转化性研究具有临床意义。
Introduction Rhabdomyolysis-induced acute kidney injury (RIAKI) can interrupt physical training and increase mortality in injured warfighters. The legal performance-enhancing drugs caffeine and ibuprofen, which can cause renal injury, are widely used by service members. Whether caffeine or ibuprofen affects RIAKI is unknown. Cilastatin treatment was recently identified as an experimental treatment to prevent RIAKI at injury. To determine potential interacting factors in RIAKI treatment, we test the hypothesis that caffeine and ibuprofen worsen RIAKI and interfere with treatment. Materials and Methods In mice, RIAKI was induced by glycerol intramuscular injection. Simultaneously, mice received caffeine (3 mg/kg), ibuprofen (10 mg/kg), or vehicle. A second cohort received volume resuscitation (PlasmaLyte, 20 mL/kg) in addition to caffeine or ibuprofen. In a third cohort, cilastatin (200 mg/kg) was administered concurrently with drug and glycerol administration. Glomerular filtration rate (GFR), blood urea nitrogen (BUN), urine output (UOP), renal pathology, and renal immunofluorescence for kidney injury molecule 1 were quantified after 24 hours. Results Caffeine did not worsen RIAKI; although BUN was modestly increased by caffeine administration, 24-hour GFR, UOP, and renal histopathology were similar between vehicle-treated, caffeine-treated, and caffeine + PlasmaLyte–treated mice. Ibuprofen administration greatly worsened RIAKI (GFR 14.3 ± 19.5 vs. 577.4 ± 454.6 µL/min/100 g in control, UOP 0.5 ± 0.4 in ibuprofen-treated mice vs. 2.7 ± 1.7 mL/24 h in control, and BUN 264 ± 201 in ibuprofen-treated mice vs. 66 ± 21 mg/dL in control, P < .05 for all); PlasmaLyte treatment did not reverse this effect. Cilastatin with or without PlasmaLyte did not reverse the deleterious effect of ibuprofen in RIAKI. Conclusions Caffeine does not worsen RIAKI. The widely used performance-enhancing drug ibuprofen greatly worsens RIAKI in mice. Standard or experimental treatment of RIAKI including the addition of cilastatin to standard resuscitation is ineffective in mice with RIAKI exacerbated by ibuprofen. These findings may have clinical implications for the current therapy of RIAKI and for translational studies of novel treatment.
登录
查看更多内容
影响因子：
1.2
作者：
Paisley, Robert D.
通讯作者：
Paisley, Robert D.
影响因子：
5.6
作者：
Zaballos M;Power M;Canal-Alonso MI;González-Nicolás MÁ;Vasquez-Jimenez W;Lozano-Lominchar P;Cabrerizo-Torrente P;Palencia-García N;Gago-Quiroga S;Ginel-Feito MD;Jiménez C;Lázaro A;González-Bayón L
通讯作者：
González-Bayón L
DOI：
10.1016/0006-291x(85)91335-x
发表时间：
1985-01-01
影响因子：
3.1
作者：
KOLLER, M;RAULF, M;KONIG, W
通讯作者：
KONIG, W
影响因子：
4
作者：
Hopkins, Benjamin S.;Li, Daniel;Dandaleh, Nader S.
通讯作者：
Dandaleh, Nader S.
甘油诱导的大鼠血红蛋白尿急性肾衰竭。
DOI：
10.1172/jci105387
发表时间：
1966
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
D. Oken;M. Arce;D. Wilson
通讯作者：
D. Wilson