Covalent binding of nitroso-sulfonamides to glutathione S-transferase in guinea pigs with delayed type hypersensitivity.

Drug induced allergies are believed to be induced by conjugates consisting of biological macromolecules and active metabolites. The present study investigated whether guinea pig glutathione S-transferase (gpGST), a protein that binds with sulfanilamide (SA) and sulfamethoxazole (SMX), could be detected in the liver cytosol fraction of guinea pigs that intraperitoneally received SA or SMX, and whether gpGST is a carrier protein. We synthesized three nitroso compounds, i.

Design, synthesis, and pharmacological activity of nonallergenic pyrazolone-type antipyretic analgesics.

To develop novel nonallergenic pyrazolone analgesics, we synthesized a series of compounds in which position 1 of the pyrazolone ring was substituted in place of the original methyl group in order to block the formation of allergenic metabolites via N-dealkylation. These pyrazolone analogues were found to show as potent an antipyretic and analgesic effect as antipyrine (AT). In an examination of allergenicity, AT induced a typical skin reaction in guinea pigs, whereas the pyrazolone analogues were inactive.

Δ9-tetrahydrocannabinol and its major metabolite Δ9-tetrahydrocannabinol-11-oic acid as 15-lipoxygenase inhibitors.

15-Lipoxygenase (15-LOX) is one of the key enzymes responsible for the formation of oxidized low-density lipoprotein, a major causal factor for atherosclerosis. Δ(9)-Tetrahydrocannabinol (Δ(9)-THC), a major component of marijuana, has suggested to suppress atherosclerosis. Although Δ(9)-THC seems to be attractive for the prevention of atherosclerosis, there is no information about whether or not 15-LOX isoform can be inhibited by Δ(9)-THC.

The stimulatory effects of caffeine with oseltamivir (Tamiflu) on light-dark behavior and open-field behavior in mice.

Abnormal behaviors and death associated with the use of oseltamivir (Tamiflu) have emerged as a major issue in influenza patients taking the drug. Here, we investigated the mechanisms underlying the effects of oseltamivir on the behavior of mice using light-dark and open-field preference tests. Oseltamivir (75 and 150 mg/kg, intraperitoneally (i.

Involvement of the GABA/benzodiazepine receptor in the axiolytic-like effect of nociceptin/orphanin FQ.

We investigated the mechanism underlying the anxiolytic actions of the neuropeptide nociceptin/orphanin FQ (N/OFQ) with an elevated plus-maze test. In mice, intracerebroventricular (i.c.

Effects of experimental diabetes on hepatic drug metabolism in rats: the activities of flavin-containing monooxygenase, the phase II conjugation reactions and glutathione related enzymes.

Hepatic drug metabolism (flavin-containing monooxygenase (FMO), glutathione related enzymes, phase II conjugation reactions) and the hepatic contents of glutathione were investigated in normal rats, alloxan induced diabetic rats and streptozotocin (STZ) induced diabetic rats. The hepatic content of reduced or oxidized glutathione, the activities of glutathione related enzymes (glutathione reductase and glutathione peroxidase) and several enzymes (p-nitrophenol glucuronosyltransferase, aryl sulphotransferase I and II) involved in conjugation reactions were lower in alloxan- and STZ-induced diabetic rats than those in normal rats. In contrast, the activities of FMO and aryl sulphotransferase IV were significantly higher in alloxan- and STZ-induced diabetic rats than those in normal rats.

Role of amygdaloid nuclei in the anxiolytic-like effect of nociceptin/orphanin FQ in rats.

We investigated the mechanism underlying the anxiolytic actions of the neuropeptide nociceptin/orphanin FQ (N/OFQ) using the elevated plus-maze test and T-maze test. Microinfusions of N/OFQ (10 or 32pmol) into the central amygdala (ACE) increased the time spent in the open arms of the elevated plus-maze (anxiolytic-like effects), whereas microinfusions of N/OFQ (10, 32 or 100 pmol) into the basolateral amygdala (ABL) did not affect the time spent in the open arms. Moreover, microinfusions of N/OFQ (32 pmol) into the ACE impaired escape performance from the open arms of the elevated T-maze (anxiolytic-like effects), but did not change inhibitory avoidance of the open arms.

Acid sphingomyelinase inhibition suppresses lipopolysaccharide-mediated release of inflammatory cytokines from macrophages and protects against disease pathology in dextran sulphate sodium-induced colitis in mice.

Lipopolysaccharide (LPS) and inflammatory cytokines cause activation of sphingomyelinases (SMases) and subsequent hydrolysis of sphingomyelin (SM) to produce a lipid messenger ceramide. The design of SMase inhibitors may offer new therapies for the treatment of LPS- and cytokine-related inflammatory bowel disease. We synthesized a series of difluoromethylene analogues of SM (SMAs).

Protective effects of carotenoids from saffron on neuronal injury in vitro and in vivo.

Crocus sativus L. (saffron) has been used as a spice for flavoring and coloring food preparations, and in Chinese traditional medicine as an anodyne or tranquilizer. Our previous study demonstrated that crocin, a carotenoid pigment of saffron, can suppress the serum deprivation-induced death of PC12 cells by increasing glutathione (GSH) synthesis and thus inhibiting neutral sphingomyelinase (nSMase) activity and ceramide formation.