Tachio Aimoto

Hydroxyl Radical Scavenging Activity of Nonsteroidal Anti-Inflammatory Drugs

The hydroxyl radical (.OH)-scavenging activity of d-2-[4-(3-methyl-2-thienyl)phenyl]propionic acid (M-5011), a novel nonsteroidal anti-inflammatory drug (NSAID), and that of several other NSAIDs were investigated by the hyaluronic acid (HA) degradation method and the electron spin resonance (ESR) spin-trapping technique. The superoxide anion (.O2-)-scavenging activity of M-5011 was also measured by the ESR technique. (1) M-5011 and the other NSAIDs examined inhibited the degradation of HA induced by the Fenton reaction system in a dose-dependent manner. (2) M-5011 and the other NSAIDs scavenged .OH directly in a dose-dependent manner. (3) M-5011 was the most potent drug among the NSAIDs tested regarding the scavenging activity of .OH as follows; M-5011 > indomethacin > ketoprofen = suprofen > aspirin. The .OH-scavenging activity of M-5011 was potent in comparison with that of oxidized glutathione (GSSG), an endogenous .OH scavenger. (4) M-5011 did not scavenge .O2-; nor did GSSG. These results suggest that M-5011 acts as a scavenger of .OH at sites with inflammatory lesions.

Induction of hepatic microsomal drug-metabolizing enzymes by sulfur-containing metabolites of chlorinated benzenes in rats

3,5-Dichlorophenyl methyl sulfide and its oxidized compounds, metabolites of m-dichlorobenzene, increased the activity of aniline hydroxylase and aminopyrine N-demethylase and the content of cytochromes P-450 and b5 in rat liver microsomes. Hexobarbital sleeping time was reduced by these three compounds. After the administration of the sulfide to rats, 3,5-dichlorophenyl methyl sulfone appeared in blood, liver, and kidneys, and remained detectable in the blood and the tissues between 120 and 240 hr. The sulfone was considered to play a principal role in the induction by these compounds. Other chlorophenyl methyl sulfones also showed similar induction activity.

The Effect of High-Intensity Electric-Field Exposure on Lipid Peroxidation in Blood and Organs in Rats

The blood lipid peroxide level of non-exposed and exposed (60-Hz electric field) groups of 8-week-old rats gradually increased over 55 weeks. However, the increasing rate was significantly lower in the exposed rats. In the controls, serum biochemical parameters of the 63-week-old rats related to hepatic function were significantly different compared with those of the young rats. In the exposed rats, the age-dependent differences were smaller and/or disappeared. Electric-field exposure may influence the increase in lipid peroxidation and the alteration in serum enzyme activities accompanying aging.