Biomedical subjects

T Zima

Publications and source records attributed to T Zima.

112 records · Page 7Linked to original sources

PubMed1991

Plasma xanthine oxidase and resistance to hypoxia: effect of purines and alcohol administration.

The administration of allopurinol significantly increased resistance to repeated hypobaric hypoxia, while hypoxanthine decreased it. The administration of adenine or inosine (25 mg/kg) was without effect. The results show pathogenic significance of xanthine oxidase-dependent production of free oxygen radicals in posthypoxic damage. In other experiments, the administration of 50% ethanol (12 ml/kg) by gastric catheter increased plasma xanthine oxidase activity in both rats and hamsters.

Adenine↗

PubMedDate not supplied

Oxidative stress, metabolism of ethanol and alcohol-related diseases.

Alcohol-induced oxidative stress is linked to the metabolism of ethanol. Three metabolic pathways of ethanol have been described in the human body so far. They involve the following enzymes: alcohol dehydrogenase, microsomal ethanol oxidation system (MEOS) and catalase. Each of these pathways could produce free radicals which affect the antioxidant system. Ethanol per se, hyperlactacidemia and elevated NADH increase xanthine oxidase activity, which results in the production of superoxide. Lipid peroxidation and superoxide production correlate with the amount of cytochrome P450 2E1. MEOS aggravates the oxidative stress directly as well as indirectly by impairing the defense systems. Hydroxyethyl radicals are probably involved in the alkylation of hepatic proteins. Nitric oxide (NO) is one of the key factors contributing to the vessel wall homeostasis, an important mediator of the vascular tone and neuronal transduction, and has cytotoxic effects. Stable metabolites--nitrites and nitrates--were increased in alcoholics (34.3 +/- 2.6 vs. 22.7 +/- 1.2 micromol/l, p < 0.001). High NO concentration could be discussed for its excitotoxicity and may be linked to cytotoxicity in neurons, glia and myelin. Formation of NO has been linked to an increased preference for and tolerance to alcohol in recent studies. Increased NO biosynthesis also via inducible NO synthase (NOS, chronic stimulation) may contribute to platelet and endothelial dysfunctions. Comparison of chronically ethanol-fed rats and controls demonstrates that exposure to ethanol causes a decrease in NADPH diaphorase activity (neuronal NOS) in neurons and fibers of the cerebellar cortex and superior colliculus (stratum griseum superficiale and intermedium) in rats. These changes in the highly organized structure contribute to the motor disturbances, which are associated with alcohol abuse. Antiphospholipid antibodies (APA) in alcoholic patients seem to reflect membrane lesions, impairment of immunological reactivity, liver disease progression, and they correlate significantly with the disease severity. The low-density lipoprotein (LDL) oxidation is supposed to be one of the most important pathogenic mechanisms of atherogenesis, and antibodies against oxidized LDL (oxLDL) are some kind of epiphenomenon of this process. We studied IgG oxLDL and four APA (anticardiolipin, antiphosphatidylserine, antiphosphatidylethanolamine and antiphosphatidylcholine antibodies). The IgG oxLDL (406.4 +/- 52.5 vs. 499.9 +/- 52.5 mU/ml) was not affected in alcoholic patients, but oxLDL was higher (71.6 +/- 4.1 vs. 44.2 +/- 2.7 micromol/l, p < 0.001). The prevalence of studied APA in alcoholics with mildly affected liver function was higher than in controls, but not significantly. On the contrary, changes of autoantibodies to IgG oxLDL revealed a wide range of IgG oxLDL titers in a healthy population. These parameters do not appear to be very promising for the evaluation of the risk of atherosclerosis. Free radicals increase the oxidative modification of LDL. This is one of the most important mechanisms, which increases cardiovascular risk in chronic alcoholic patients. Important enzymatic antioxidant systems - superoxide dismutase and glutathione peroxidase - are decreased in alcoholics. We did not find any changes of serum retinol and tocopherol concentrations in alcoholics, and blood and plasma selenium and copper levels were unchanged as well. Only the zinc concentration was decreased in plasma. It could be related to the impairment of the immune system in alcoholics. Measurement of these parameters in blood compartments does not seem to indicate a possible organ, e.g. liver deficiency.

Adult↗

PubMedDate not supplied

Acute dosage with dexrazoxane, but not doxorubicin, is associated with increased rates of hepatic protein synthesis in vivo.

An investigation was carried out into the effects of dexrazoxane and doxorubicin on hepatic protein synthesis in vivo. The protocol included 8 groups of rats and involved a pretreatment stage of 30 min followed by a treatment stage of either 2.5 or 24 h. Male Wistar rats (=0.15-0.20 kg) were pretreated with either dexrazoxane (100 mg/kg; 5 ml/kg) or saline (0.15 mol/l NaCl; 5 ml/kg). At 30 min after the pretreatment, rats were again injected with either doxorubicin (5 mg/kg; 10 ml/kg) or saline (0.15 mol/l NaCl; 10 ml/kg) in the treatment phase. Rats were sacrificed at either 2.5 or 24 h after the last doxorubicin or saline injection. Rate of protein synthesis were measured 10 min prior to sacrificing rats, with a flooding dose of L-[4-3H]phenylalanine. Liver was analyzed for the protein synthetic capacity (Cs, mg RNA/g protein), the fractional rate of protein synthesis (k(s), %/d), and the RNA activity (kRNA mg protein/d/mg RNA). Complementary analysis included plasma albumin, total protein and activities of alkaline phosphatase, and aspartate aminotransferase. In the 2.5-h study, doxorubicin alone had no effect on any of the above variables. Dexrazoxane alone increased Cs, k(s) and kRNA at 2.5 h. Combined dexrazoxane + doxorubicin increased hepatic Cs and k(s) with concomitant reductions in total plasma protein. In the 24-h study, doxorubicin alone had no effect on any of the variables. Dexrazoxane alone had no effect on either Cs, k(s), or kRNA but raised plasma activities of alkaline phosphatase and aspartate aminotransferase. Combined dexrazoxane + doxorubicin increased Cs and k(s) and decreased total plasma protein and increased plasma aspartate aminotransferase activities at 24 h. In conclusion, there is no evidence that acutely doxorubicin per se has measurable effects on hepatic protein synthesis in vivo in an acute period. However, acutely dexrazoxane increases hepatic protein synthesis, which may represent its putative cytotoxic effects, as indicated by raised serum activities of liver enzymes. A combination of both dexrazoxane + doxorubicin appears to have a greater effect in increasing liver protein synthesis than dexrazoxane alone.

Alkaline Phosphatase↗

PubMedDate not supplied

The influence of chronic moderate ethanol administration on NADPH-diaphorase (nitric oxide synthase) activity in rat brain.

Nitric oxide synthase (NOS), the enzyme with reduced nicotinamide-adenine dinucleotide phosphate (NADPH)-diaphorase activity, generates nitric oxide (NO) which is an important bioregulatory molecule in the nervous, immune, and cardiovascular systems. NOS is linked to non-adrenergic non-cholinergic (NANC) neuronal pathways and modulation of the N-methyl-D-aspartate receptors, yet its modification by ethanol has been little explored. A possible modification by chronic ethanol administration of activity and/or localization of NADPH-diaphorase (NO-synthase) in rat brain may thus provide the pathogenic basis of alcohol-induced brain injury. When female Wistar rats were treated chronically with ethanol for 50 days, the NADPH-diaphorase staining of granular neurons and neurons located in the molecular layer of the cerebral cortex was significantly reduced. Chronic ethanol consumption led to a significant reduction in NADPH-diaphorase staining in the superficial layers of the superior colliculus. The number of NADPH-diaphorase-positive neurons was significantly reduced (P < 0.001) in the stratum zonale and stratum griseum superficiale (by 42.3-65.6% of control values). This could alter synaptic processes in the highly organized structures involved in oculomotor and somatic motor coordination and thus contribute to the motor disturbances which are associated with alcohol abuse.

Analysis of Variance↗