Ponnapakkam Tulasi, Bongay-Williams Kyla, Beamon Teresa, Hooks Royce, Cheatham Degrick, Goyal Navneet, Anbalagan Muralidharan, Foroozesh Maryam
Department of Chemistry, Xavier University of Louisiana, 1 Drexel Dr., New Orleans, LA 70125, USA.
Department of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Toxicol Rep. 2021 Jul 31;8:1521-1526. doi: 10.1016/j.toxrep.2021.07.022. eCollection 2021.
We have previously reported that treating triple-negative tumor bearing nude mice with intraperitoneal (ip) 10 mg/kg body weight of (S,E)-3-hydroxy-2-(2-hydroxybenzylidene)aminotetradecylpropanamide, a ceramide analog, 5 days per week for 3 weeks, was shown not only to suppress tumor growth but also to reduce metastasis. Studies reported here focus on determining the toxicity of this drug in the nude mice. During the first study, treated animals (single intraperitoneal (ip) injection, 0, 40, 80 and 120 mg/kg body weight) were closely monitored for 14 days for any signs of illness or death. No mice were lost in any animal groups; however, hepatic serum enzymes were elevated, and hepatic and heart tissue damages were found in the highest dosage group. The subsequent study was performed using a lower dosage range (single ip injection, 0, 25, 50 and 75 mg/kg body weight), which resulted in no significant toxicity. All tested parameters were within normal ranges, with no observed irregularities. Our findings show that a single ip dose of this ceramide analog induced liver and heart toxicity at 120 mg/kg but not at doses of 80 mg/kg body weight or lower.
我们之前曾报道，每周5天、连续3周给荷三阴性肿瘤的裸鼠腹腔注射(ip) 10毫克/千克体重的(S,E)-3-羟基-2-(2-羟基亚苄基)氨基十四烷基丙酰胺（一种神经酰胺类似物），结果显示不仅能抑制肿瘤生长，还能减少转移。本文报道的研究聚焦于确定该药物对裸鼠的毒性。在第一项研究中，对接受治疗的动物（单次腹腔(ip)注射，0、40、80和120毫克/千克体重）进行了14天的密切监测，观察是否有任何疾病或死亡迹象。任何动物组均无小鼠死亡；然而，在最高剂量组中发现肝血清酶升高，且存在肝和心脏组织损伤。随后的研究使用了较低的剂量范围（单次ip注射，0、25、50和75毫克/千克体重），结果未发现明显毒性。所有测试参数均在正常范围内，未观察到异常情况。我们的研究结果表明，单次腹腔注射该神经酰胺类似物，在120毫克/千克体重时会诱导肝和心脏毒性，但在80毫克/千克体重或更低剂量时则不会。
