Reference

Reye's syndrome: salicylates and mitochondrial functions

Reye's syndrome: salicylates and mitochondrial functions. Martens, Margaret E.; Lee, Chuan Pu (Sch. Med., Wayne State Univ., Detroit, MI 48201, USA). Biochem. Pharmacol., 33(18), 2869-76 (English) 1984. CODEN: BCPCA6. ISSN: 0006-2952. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 63 The effects of aspirin (ASA) [50-78-2] and related compds. in the presence of Ca2+ on the oxidative metab. of isolated rat liver mitochondria were studied. Intact mitochondrial prepns. preincubated with ASA and Ca2+ exhibited a transient stimulation of the state 4 respiratory rate with NAD+-linked substrates, followed by an inhibition which could not be released by the addn. of ADP or uncoupler. Max. respiratory rates were achieved by subsequent addn. of NAD+ or succinate. The Ca2+-transport inhibitors ruthenium red and ethylene glycol-bis(b-aminoethyl ether) N,N'-tetraacetic acid (EGTA) prevented these effects. Five brands of com. aspirin were tested and were as effective as purified ASA. Acetaminophen [103-90-2] could reproduce these effects only at much higher (310-fold) concns. Other salicyl derivs. showed results qual. similar to ASA, with potencies in the order: salicylic acid [69-72-7] >>> ASA ? salicyl alc. [90-01-7] 3 catechol [120-80-9] > salicylamide [65-45-2], salicylate being approx. 10-fold more potent than ASA. The magnitude of the effect seen depended on the Ca2+ (endogenous and exogenous) and salicylate concns./mg mitochondrial protein, and on the length of the preincubation. Added inorg. phosphate was also required. That salicylate and Ca2+ induce an increase in the permeability of the mitochondrial inner membrane was demonstrated by the observation that 90% of the intramitochondrial NAD(P)+ was released into the surrounding medium upon preincubation of intact mitochondria with these agents. Salicylate and Ca2+ had virtually no effect on respiration with succinate (and rotenone) as substrate at salicylate concns. which markedly affected NAD+-linked substrate oxidn. The presence of rotenone in the preincubation mixt. prevented the damaging effects of salicylate and Ca2+ on the mitochondrial membrane, suggesting that the redox state of intramitochondrial pyridine nucleotides can modulate these effects. The results reported here are similar to those reported previously for the effects of Reye's plasma and allantoin [97-59-6] and Ca2+, and indicate that, like these agents, salicylate and salicyl compds. can potentiate the Ca2+-induced damage to the mitochondrial inner membrane and may be another factor responsible for Reye's syndrome.

Inhibitory effects of salicylate on contractility in skeletal muscle

Inhibitory effects of salicylate on contractility in skeletal muscle. Suarez-Kurtz, G.; Da Costa, M. Josefina Braga; Coutinho, Solange (Inst. Cienc. Biomed., Univ. Fed. Rio de Janeiro, Rio de Janeiro 21944, Brazil). J. Pharmacol. Exp. Ther., 230(2), 478-82 (English) 1984. CODEN: JPETAB. ISSN: 0022-3565. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Salicylate [69-72-7] (1-5 mM) had no effect on the peak amplitude Pt) of twitches elicited at 0.05 to 0.5 Hz, but depressed the Pt in frog and toad "toe" muscles stimulated at 5 to 10 Hz. The maximal tetanic tension (Po) was not reduced significantly by salicylate, but the time to reach Po was increased to several seconds. K-induced contractures were reduced by ~40 and 50%, resp., in the presence of 5 and 10 mM salicylate. Pretreatment with salicylate (5 mM) reduced the twitch potentiation by quinine [130-95-0], shortened the duration of twitches in caffeine [58-08-2]-treated muscles and inhibited the caffeine and the quinine-induced contractures. Muscles in contracture because of a previous exposure to quinine relaxed promptly upon addn. of salicylate to the bathing medium. The inhibitory effects of salicylate on Pt on Po and on K- or drug-induced contractures were reversible and were not affected by changes in pH between 7.5 and 6.5. Salicylate depressed the caffeine-rapid cooling contractures (RCC). In toad muscles, this effect was affected markedly by the order in which caffeine and salicylate were applied. Blockade of the caffeine-RCC by salicylate was enhanced by lowering the pH of the medium. Salicylamide [65-45-2] (1-5 mM) reproduced the effects of salicylate on the caffeine- and the quinine-induced contractures aznd the caffeine-RCC. In addn., salicylamide reduced the twitch tension. Salicylate and salicylamide may affect Ca-sequestration by the sarcoplasmic reticulum.