RESUMEN
To our knowledge, no reports on the impact of nicotine on the enzyme activity of the lysosomal system have been published yet. The study which is reported here is probably one of the first analyses of the models of lysosomal hydrolases of the liver and kidney of experimental mice which were exposed to various doses of nicotine. The aim of our experimental study was to analyze the impact of nicotine administered for 4 or 8 days in the dosage of 12 and 20 mg/kg body weight, respectively, on the activity of acid phosphatase and cathepsins D and L, i.e. lysosomal hydrolases of the liver and kidney of mice. The experimental group constituted 60 Swiss male mice, aged 8-9 weeks, of average body weight of 23.4 +/- 1.2 grams. We came to the following conclusions after the completion of the experimental study and laboratory analyses: - nicotine injected once a day in the dosage of 12 mg and 20 mg/kg body weight for 4 and 8 days caused a significant increase in the activity of acid phosphatase, and cathepsins D and L in the liver and kidney of the studied mice. The range of observed changes was related to the organ, the dosage and administration time; - the increase in the activity of studied enzymes after administering nicotine may indicate that the alkaloid exhibits destabilizing activity in lysosomal membranes of the liver and kidney cells, therefore it may affect metabolic pathways of those organs.
Asunto(s)
Fosfatasa Ácida/efectos de los fármacos , Catepsina D/efectos de los fármacos , Riñón/enzimología , Hígado/enzimología , Lisosomas/efectos de los fármacos , Nicotina/farmacología , Fosfatasa Ácida/metabolismo , Animales , Catepsina D/metabolismo , Esquema de Medicación , Lisosomas/metabolismo , Masculino , RatonesRESUMEN
BACKGROUND: Intermittent clamping (IC) of the portal triad is an effective method of protecting the liver from ischemia-reperfusion injury (IR). In clinical practice, this method is employed during a resection, but its mechanism is still not clear. OBJECTIVES: To evaluate the effect of IC on rat liver and determine its mechanisms. MATERIALS AND METHODS: Wistar rats were submitted to 60-min IC (cycles of 12-min clamping followed by 4-min reperfusion), and the samples were collected after 1, 6, and 72 hrs of reperfusion. We determined the serum activity of alanine aminotransferase (ALT), and measured the concentration of TNF-α, malondialdehyde (MDA) and myeloperoxidase (MPO) in liver homogenates. The apoptosis of hepatocytes was evaluated immunohistochemically. RESULTS: When compared to the IR rats, the activity of ALT decreased in the IC group in all periods of observation (the highest decrease of ~48% after 1 hr of reperfusion). When compared to the IR group, a statistically significant decrease (p < 0.05) in the TNF-α concentration (~33%) in the IC rats occurred only after 1 hr of reperfusion, and it was accompanied by a decrease in the MPO concentration after 1 and 6 hrs of reperfusion. IC reduces the effects of reactive oxygen species (ROS) activity, which has been confirmed by a statistically significant decrease in MDA concentration by 25%-35% in all studied periods. The limitation of hepatocytes apoptosis due to IC occurs in the early (~26%; p < 0.05) and late (~45%; p < 0.01) phases of reperfusion. CONCLUSIONS: The use of IC in early phase of reperfusion brings about a decrease in TNF-α release, which can be related to liver injury due to neutrophil infiltration and apoptotic cell reduction. It seems that the reduction of lipid peroxidation may also limit the liver injury.