RESUMEN
BACKGROUND AND PURPOSE: Hepatic steatosis may be associated with an increased γ-glutamyltransferase (γ-GT) levels. Ischaemia-reoxygenation (IR) injury causes several deleterious effects. We evaluated the protective effects of a selective inhibitor of γ-GT in experimentally induced IR injury in rats with obesity and steatosis. EXPERIMENTAL APPROACH: Otsuka Long-Evans Tokushima Fatty (OLETF) rats with hepatic steatosis were used in the current study. The portal vein and hepatic artery of left lateral and median lobes were clamped to induce ischaemia. Before clamping, 1 ml of saline (IR group) or 1-ml saline containing 1 mg·kg-1 body weight of GGsTop (γ-GT inhibitor; IR-GGsTop group) was injected into the liver via the inferior vena cava. Blood flow was restored after at 30 min of the start of ischaemia. Blood was collected before, at 30 min after ischaemia and at 2 h and 6 h after reoxygenation. All the animals were killed at 6 h and the livers were collected. KEY RESULTS: Treatment with GGsTop resulted in significant reduction of serum ALT, AST and γ-GT levels and hepatic γ-GT, malondialdehyde, 4-hydroxy-2-nonenal and HMGB1 at 6 h after reoxygenation. Inhibition of γ-GT retained normal hepatic glutathione levels. There was prominent hepatic necrosis in IR group, which is significantly reduced in IR-GGsTop group. CONCLUSION AND IMPLICATIONS: Treatment with GGsTop significantly increased hepatic glutathione content, reduced hepatic MDA, 4-HNE and HMGB1 levels and, remarkably, ameliorated hepatic necrosis after ischaemia-reoxygenation. The results indicated that GGsTop could be an appropriate therapeutic agent to reduce IR-induced liver injury in obesity and steatosis.
Asunto(s)
Hígado Graso , Daño por Reperfusión , Animales , Isquemia , Hígado , Malondialdehído , Ratas , Daño por Reperfusión/tratamiento farmacológico , gamma-GlutamiltransferasaRESUMEN
CASE REPORTS: We experienced two cases of acute lead poisoning due to occupational exposure to lead. The patients were engaged in stripping off antirust compounds including Pb from a bridge and re-painting it at the same work place. Both patients exhibited colic, arthralgia, and anemia. Blood lead levels were 73.1 microg/dl and 96.3 microg/dl. Intravenous CaEDTA chelation therapy was therefore performed. After chelation, blood lead levels decreased and symptoms gradually disappeared. DISCUSSION: Although the patients were working with protective equipment, the workplace was in the mountains and there was no water for washing. The patients were thus unable to washing their hands and faces. We assume that they swallowed lead dust left on their hands and faces when they removed their clothing, and believe that this poisoning occurred due to lack of knowledge sufficient for protection.
Asunto(s)
Intoxicación por Plomo/etiología , Enfermedades Profesionales/etiología , Exposición Profesional , Adulto , Quelantes/administración & dosificación , Ácido Edético/administración & dosificación , Eritrocitos/efectos de los fármacos , Eritrocitos/patología , Humanos , Intoxicación por Plomo/sangre , Intoxicación por Plomo/tratamiento farmacológico , Masculino , Equipos de Seguridad , Resultado del TratamientoRESUMEN
An analytical method using a combination of solid-phase extraction (SPE) and gas chromatography with a flame thermionic detector (GC/FTD) was developed for determination of N-methyl-2-pyrrolidone (NMP), N-methylsuccinimide (MSI), and 2-hydroxy-N-methylsuccinimide (2-HMSI) in human urine. The SPE cartridge of poly(divinylbenzene/hydroxymethacrylate) used was directly loaded with urine sample, followed by elution with methyl isobutyl ketone (MIBK) and subsequent centrifugation, and the supernatant was injected into the capillary GC using a DB1701. This method allowed efficient separation of NMP, MSI, and 2-HMSI, which were nearly free of interference by other GC peaks arising from urine. Recoveries of NMP, MSI, and 2-HMSI from the SPE cartridge were about 98, 101, and 67%, respectively, with limits of detection of 0.04, 0.02, and 0.06 mg/L, respectively, which met the regulatory requirements. The present method was used for assay in biological monitoring of workers exposed to NMP in their occupational environment.