Inhibitory effect of bis(2-aminohexyl) disulfide and bis(2-amino-3-phenylpropyl) disulfide on several mouse inflammations.
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.
Kohama
Y
Y
Faculty of Pharmaceutical Sciences, Osaka University, Japan.
Kayamori
Y
Y
Katayama
Y
Y
Murayama
N
N
Itoh
M
M
Tanaka
K
K
Tsuboi
H
H
Sakaguchi
N
N
Mimura
T
T
D000588:Amines / Q000008:administration & dosage / Q000494:pharmacology*; D000662:Amphetamines / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects; D004220:Disulfides / Q000008:administration & dosage / Q000494:pharmacology*; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D006168:Guinea Pigs; D006968:Hypersensitivity, Delayed; D066298:In Vitro Techniques; D007249:Inflammation / Q000188:drug therapy*; D017114:Liver Failure, Acute / Q000188:drug therapy; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D010538:Peritonitis / Q000188:drug therapy; D013440:Sulfides / Q000008:administration & dosage / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism
D000588:Amines; D000662:Amphetamines; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004220:Disulfides; D013440:Sulfides; D013481:Superoxides; C058067:bis(1-thio-2-amino-3-phenylpropane); C075124:bis(2-aminohexyl)disulfide