Pharmacological Research Communications, Vol. 20, Supplement Ii, 1988
EFFECT OF BSO AND PHORONE ON GSH LEVELS IN RATS WITH GASTRIC ULCER
L. Micheli, A. I.Fiaschi, ~. Giorg| Istituodi di Farmacologia, Facolt~di Medicine e Chirurgia, UnlverslttJ degli Studt di Siena. Key words: elutethione, BSO,Phorone, HCEtOH, Serotonine. Olutethlone (L-v-glutemylcystelnylglyclne= 08H) plays an essential role In dstoxlflcetlon of drugs, in maintenanceof cellular redox states end cell membrane integrity, indeeddepletion of cellular (LSH and subsequent exacerbation of toxicity is an accepted procedure for demostreting that a reactive electrophlHc compound may be responstb]e for chemical-induced toxicity. Current methods of investigating the involvement of 05H in the expression of toxic response to chemical, relies on e depletion of cellular 08H by several agents which act as competitive substretes for glutathione-s-trasferosa or by inhibition for its synthesis, The most widely used compound in the letter group is buthionine sulfoximine (B~>O) e tightly bound inhibitor of v-glutemyl-cysteine syntetase. Another ~H-depleting agent is phorone (2,6-dtmethyl-2,5 heptedlen-~ione) which incr~
the glutethione-.s-trasferese activity, In previous our experiment we observed that,
following administration in rats of HC1in EtOHabsolute (EtOHec.) or 5erotonine, both the maximum ~mooe lnduclng ulcer and the mlnlmum C~H level ls reached alter 5 hours, For these reasons we treated a first group of animals with BSO (4mM/Kg diesolved in saline s.c.) end after 4 hours hall" of them reo~ived HCI 0.6N in ethanol absolute (6 rni/Kg as) and the second half ser'otonine (80 mg/Ko dissolved in saline s.c.), lhe secondgroup was treated with phorone ( 250mg/Kg dissolved in corn oil i,p,) and after 2 hours half of them received EtOHec.and the secondhalf serotonine, both at the same dosagesbefore Indicated.Control animals received only saline s.c. or corn oll i.p.. All used animals ( 60 male Wister rats average weight 250 g) were fasted 24 hours before the experiment. Rats were ~ r i f i e d by decapitation at the same hour of day (16:00) 5 hours after the treatment with EtOHac. c,r 5erotontne: Blood am liver were collected and processed as described by Oiorgl. Total aSH was determined by the Tietze's method end the protein content according to Lowry. The difference in means have been evaluated by Student's test (two-tailed). 8:30 and phorone significantly inhibit the protein synthesis as described by Costa. These results show that pllorone end BSO deplete (~H in blood end liver differently. Such an effect happens also When a stress condition has been provoked. Must by pointed out that rats survived until sacrifice. Hence B,50and phorone can be an adequatetool for studies aimed at charac~rizing the role of O,SHin the metabolism and toxicity of chemicals. Costa L. 6., S.D. Murphy (1986) B i ~ . Phorm~ol. 3~: 3383-3388. Giorgi 6., Micheli L., ~cjre 6. (1984) IRC5 Hed. ~i. 12: 560- 561. Lowry, O. H., Ro~,brough H. d., F~"r D. L. ( 197 ! ) d. Biol. Clam. ! 93: 26~-272. Tielze F. (1969) Anal. Biachem. 27: 502-522.