Kohama Y, Kayamori Y, Katayama Y, Murayama N, Itoh M, Tanaka K, Tsuboi H, Sakaguchi N, Mimura T
Faculty of Pharmaceutical Sciences, Osaka University, Japan.
Chem Pharm Bull (Tokyo). 1992 Nov;40(11):3013-6. doi: 10.1248/cpb.40.3013.
The anti-inflammatory profile of the analogues of bis(2-aminopropyl) disulfide dihydrochloride with butyl (compd. II) and phenyl (compd. III) instead of the methyl group was studied in several mouse models related to phagocyte functions. The test samples were administered 2-3 h before the inflammatory stimulation or the peak of inflammation. Subcutaneously administered, compds. II and III significantly inhibited serotonin-induced paw edema in a dose-dependent manner (50% inhibitory dose values: 10 and 5 mg/kg, respectively), when orally administered at 25 mg/kg, these compounds were significantly effective, but their potencies were weaker. Neither compound had any irritant activity when administered at a dose of 12.5 micrograms/5 microliters/paw into the paw. In a sheep red blood cells (SRBC)-induced delayed-type hypersensitivity (DTH) reaction model, compd. II (25 mg/kg, s.c.) significantly inhibited the DTH responses when administered at two different times in relation to the time of challenge. However, there was only slight inhibition by compd. III (25 mg/kg, s.c.) on paw edema formation when administered 14 h after secondary immune response. In a model of experimental acute hepatic failure induced by successive injections of Propionibacterium acnes and lipopolysaccharide, both compounds increased mouse survived, compared with the control mice, and kept the serum levels of components involved in hepatic failure to nearly normal levels. These results demonstrate that compds. II and III possess an inhibitory effect on inflammation related to phagocytes.
在几种与吞噬细胞功能相关的小鼠模型中，研究了用丁基（化合物II）和苯基（化合物III）取代甲基的双（2-氨基丙基）二硫化物二盐酸盐类似物的抗炎特性。在炎症刺激或炎症高峰期前2-3小时给予测试样品。皮下给药时，化合物II和III以剂量依赖性方式显著抑制血清素诱导的爪肿胀（50%抑制剂量值分别为10和5mg/kg），口服给药25mg/kg时，这些化合物有显著效果，但效力较弱。当以12.5微克/5微升/爪的剂量注射到爪中时，两种化合物均无刺激活性。在绵羊红细胞（SRBC）诱导的迟发型超敏反应（DTH）模型中，化合物II（25mg/kg，皮下注射）在与攻击时间相关的两个不同时间给药时，显著抑制DTH反应。然而，在二次免疫反应后14小时给药时，化合物III（25mg/kg，皮下注射）对爪肿胀形成只有轻微抑制作用。在连续注射痤疮丙酸杆菌和脂多糖诱导的实验性急性肝衰竭模型中，与对照小鼠相比，两种化合物均提高了小鼠的存活率，并使参与肝衰竭的血清成分水平保持在接近正常水平。这些结果表明，化合物II和III对与吞噬细胞相关的炎症具有抑制作用。
