Intoxicación por ácido acetilsalicílico, fisiopatología y manejo / Physiopathology and management of acetylsalicylic acid intoxication

Acetylsalicylic acid (ASA) intoxication is potentially lethal. After ingestion, AAS is rapidly transformed into salicylic acid that dissociates into an hydrogen ion plus salicylate. Salicylate is the main form of AAS in the body and produces multiple alterations. Initially, the stimulation of the ventilatory center promotes a respiratory alkalosis. Then, the mitochondrial dysfunction induced by salicylate, will generate a progressive metabolic acidosis due to the accumulation of ketoacids, lactic acid and dicarboxylic acids among others. Another alterations include hydro electrolytic disorders, gastrointestinal lesions, neurological involvement, ototoxicity and coagulopathy. The correct handling of acetylsalicylic acid intoxication requires an thorough knowledge of its pharmacokinetics and pharmacodynamics. Treatment consists in life support measures, gastric lavage, activated charcoal and urinary alkalization to promote the excretion of salicylates. In some occasions, it will be necessary to start renal replacement therapy as soon as possible.

Salicylate-induced changes of synaptic ultrastructures in the rat auditory center: a pilot study / 中国耳鼻咽喉头颈外科

OBJECTIVE To observe the changes of synaptic ultrastructures in the rat auditory center after long-term salicylate administration and to elucidate the role of neuroplasticity in some areas of the CNS and its involvement in tinnitus. METHODS The rats were divided into 4 groups: the control group, the acute treatment group, the chronic treatment group, and the recovery group. We investigated ultrastructural alterations in the synapses of inferior colliculus (IC), auditory center (AC) and cerebellum (CRB) by transmission electron microscopy. RESULTS There were more synaptic vesicles (tIC=-4. 61, tAC=-7. 00, P＜0. 01), with greater postsynaptic densities(tIC=-4. 72,P＜0. 01; tAc=-3. 15, P＜0. 05), longer synaptic active zone (tIC=-4. 89, tAC=-3. 48, P＜ 0. 01), and increased synaptic interface curvature (tIC=-2. 32, tAC=-3. 17, P＜0. 05) in the chronic treatment group, as compared with the control group. There were more synaptic vesicles but no other changes in the acute salicylate-treatment group(tIC=-10. 57, tAC=-8. 34, tCRB=-9. 18,P ＜0. 01). CONCLUSION These findings showed that long-term salicylate administration have induced synaptic ultrastructural changes in the IC and AC because of neuroplasticity. These structural changes may result in increased speed and efficacy of chemical synaptic transmission. Alterations to neuroplasticity of the auditory center pathway may lead to tinnitus.

Effect of sweetener and flavoring agent on oxidative indices, liver and kidney function levels in rats.

Food additives while attract consumers, improve quality, control weight and replace sugar, may affect seriously children and adults health. Here, we investigated the adverse effects of saccharin and methylsalicyltaes as sweetener and flavoring agent on lipid profile, blood glucose, renal, hepatic function and oxidative stress/antioxidants (lipid peroxidation, catalase and reduced glutathione in liver tissues). Saccharin and methylsalicylate were administered orally in young male albino rats at low and high dose for 30 days. Rats were divided into 5 groups, 1st control group, 2nd and 3rd (low and high saccharin-treated groups) and 4th and 5th (low and high methylsalicylate-treated group). Serum total cholesterol, triglyceride, glucose levels and body weight gain were found decreased in saccharin high dose group compared to control. Rats consumed high dose of saccharin showed a significant decrease in serum triglycerides, cholesterol and LDL levels. Low and high doses of saccharin exhibited a significant increase in liver function marker of ALT, AST, ALP activity, total proteins and albumin levels and renal function test (urea and creatinine levels) in comparison with control group. Further, saccharin at high dose induced significant decrease in liver GSH levels, catalase and SOD activity and increase in hepatic MDA level. Overall saccharin harmfully altered biochemical markers in liver and kidney at higher as well as lower doses. Whereas, methyl salicylates did not pose a risk for renal function and hepatic oxidative markers.

Effect of Salicylate on DPOAEs and ABRs in Guinea Pigs / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Salicylates are well-known for producing reversible hearing loss and tinnitus. However, the site and mechanism of salicylate ototoxicity remain unresolved. Recent experiments suggest that reversible biochemical and/or metabolic changes in the cochlea seem to play an important role in salicylate ototoxicity. The purpose of this study was to investigate the site of lesion in salicylate ototoxicity by audiometric study. MATERIALS AND METHOD: ABRs and DPOAEs were observed after intraperitoneal injection of 500 mg/kg of sodium salicylate on 24 ears of guinea pigs. RESULTS: Salicylate produced a significant increase in the ABR threshold. Maximum changes were obtained in 4 hours, and recovered to the baseline in 24 hours after salicylate administration. The pattern of hearing loss shown by latency-intensity function was compatible with the cochlear type of hearing loss. The echo amplitude on DPOAEs at f2=2002, 4004 Hz was significantly decreased at 2, 4, 6, 8 hours, and returned to the baseline in 24 hours after salicylate administration. The time course of the change of DPOAEs was parallel with that of ABRs. CONCLUSION: These results reflect that the cochlear outer hair cells may be the main site of lesion in salicylate ototoxicity.

Experimental study of tinnitus on electrophysiology / 中国病理生理杂志

AIM: To find the evidence of electrophysi ol ogic mechanisms associated with average spectrum of electrophysiological cochleo neural activity (ASECA), a measure of spontaneous auditory nerve activity altera tions. METHODS: The long-term salicylate treatment was used to establis h the available animal model of tinnitus, the ASECA was monitored, and the effec ts of various presented ipsilateral acoustic were investigated. RESULTS: (1) In the first treatment, ASECA decreased acutely dur ing several hours after salicylate administration. After several days (1 week an d 2 weeks) this decrease was reduced. (2) Over weeks of salicylate administratio n, the level of ASECA increased progressively, but at the end of treatment, acou stic tuning of ASECA showed a partially decreased sensitivity. (3) In control an imals, delivery of an ipsilateral noise reproduced the increase in the level of ASECA that was similar to the result observed in long-term salicylate-treated an imals. The noise (the white noise was 55-60 dB SPL) was of moderate level and it slightly elevated CAP thresholds at higher frequencies. CONCLUSION: In the long-term salicylate-treated animals, the ASE CA-1 kHz increased reflects strongly increased synchronized activity in the audi tory nerve.