Biochemical genetics of methylglyoxal dehydrogenases in the laboratory rat (Rattus norvegicus)

A genetic locus controlling the electrophoretic mobility of a methylglyoxal dehydrogenase (EC 1.2.1.23) in the rat is described. The locus, designatedMgd1, is expressed in liver and kidney. Inbred rat strains have fixed either alleleMgd1 ^a or alleleMgd1 ^b . Codominant expression is observed in heterozygotes, providing evidence for a tetrameric enzyme structure. Backcross progenies showed the expected 1:1 segregation ratio, and there is evidence thatMgd1 is linked toPep3 andFh1 on chromosome 13. There is also evidence for two additional methylglyoxal dehydrogenases:Mgd2, present in liver and kidney, andMgd3, present only in heart.Supported by the Deutsche Forschungsgemeinschaft (Grant Be 352/18-1).     

Comparisons between the inorganic content of healthy and hypertensive rat tissues by inductively coupled plasma-mass spectrometry

The inorganic contents of bone, brain, erythrocyte, heart, kidney cortex, kidney medulla, liver, lung, muscle and plasma from spontaneously hypertensive rats were compared with those of the same tissues from healthy Sprague-Dawley rats. A general inductively coupled plasma-mass spectrometry method developed for multi-element determinations of most of the elements present in biological tissues was used. Variations were found not only for major elements, as expected, but also for many trace elements in several tissues.     

The effect of methyl palmoxirate on incorporation of [U-14C]palmitate into rat brain

We examined the dose response, time course and reversibility of the effect of methyl 2-tetradecylglycidate (McN-3716, methyl palmoxirate or MEP), an inhibitor of -oxidation of fatty acids, on incorporation of radiolabeled palmitic acid ([U-¹⁴C]PA) from plasma into brain lipids of awake rats. MEP (0.1, 1 and 10 mg/kg) or vehicle was administered intravenously from 10 min to 72 hr prior to infusion of [U-¹⁴C]PA. Two hr pretreatment with MEP (0.1 to 10 mg/kg) increased brain organic radioactivity 1.2 to 1.8 fold and decreased brain aqueous radioactivity by 1.2 to 3.0 fold when compared to control values. At 10 mg/kg, MEP significantly increased brain organic fraction from 40% in controls to 85%, 30 min to 6 hr pretreatment, and resulted in a redistribution of the radiolabeled fatty acid toward triacylglycerol. MEP changed the lipid/aqueous brain ratio of incorporated [U-¹⁴C]PA from 0.67 to 5.7. The incorporation rate coefficient, k^*, was significantly increased by MEP (10 mg/kg) at 2 hr (31%), 4 hr (59%) and 6 hr (34%). All effects were reversed by 72 hr, consistent with a half-life of 2 days for carnitine palmitoyl transferase I. These results indicate that intravenous MEP may be used with [1-¹¹C]palmitic acid for studying brain lipid metabolism in vivo by positron emission tomography, as it significantly reduces the large unincorporated aqueous fraction that would result in high background radioactivity.     

Chiral pharmacokinetics of rac-flurbiprofen and pharmacodynamics of anabolic bone response in the normal rat

The route of administration of the NSAID, flurbiprofen (sq vs. po) resulted in positive and negative results respectively with regard to enhanced cancellous and cortical bone accumulation in the immature rat. This pharmacokinetic study was an effort to understand the pharmacodynamic difference between the two routes of administration observed when the same dose range of drug, given as single daily doses, had been employed in both studies. Conventional chiral pharmacokinetics were evaluated in young rats. A significant difference was observed in the T_max of the active (S)-enantiomer by both administration routes (sq 4 h and po 1 h). The bioavailability, as evaluated by AUCs favored the sq route as expected. The plasma concentrations over 18 h, at steady state, for one po dose group (0.5 mg/kg/day) fell well within the therapeutic window described by the 0.1 and 0.5 mg/kg sq doses which had demonstrated anabolic bone activity. Oral dosing had exhibited no significant bone activity. We conclude that the pharmacodynamic difference between routes of administration cannot be simply explained on a pahrmacokinetic basis. Consequently, experiments detailing the pharmacodynamics and pharmacokinetics of single and multiple dose administration of aryl-propionic acids in normal and osteopenic states need further pharmacologic study. © 1994 Wiley-Liss, Inc.     

Plasma and liver selenium levels in the rat during supplementation with 0.5, 2, 6, and 15 ppm selenium in drinking water

Plasma and liver selenium of Wistar rats were determined after 1, 3, and 6 mo supplementation with 0.5, 2, 6, or 15 ppm selenium as sodium selenite in drinking water. Plasma selenium was not different from control values at additional intake of 0.5 ppm but increased above usual levels at higher intakes. A highly significant correlation was observed between the total quantity of selenium ingested and plasma selenium after 1 mo treatment (r=0.99,p<0.01), but was less pronounced after 3 and 6 mo (0.94,p<0.05, and 0.78,p<0.05, respectively). The decrease in plasma selenium with time of treatment was more pronounced at higher intakes. There was also a highly significant correlation between total selenium intake and liver selenium concentration (r=0.99,p<0.01) after 1 mo of treatment, but this time liver selenium did not change with time, and the correlation remained highly significant throughout the investigation. Liver selenium therefore appears as a more sensitive and more representative measure of selenium intake than plasma selenium. Most supplements did not affect body weight and survival of animals, except when the diet was supplemented with 15 ppm for 6 mo; however, alterations in biochemical parameters concerning lipid status and hepatic function were observed at levels above 2.0 ppm.     

Effect of selenium and protein deficiency on selenium and glutathione peroxidase in rats

Twenty-four weanling male Wistar rats were divided into four groups fed diets containing adequate or deficient levels of selenium (0.5 ppm [+ Se] or <0.02 ppm [−Se] and protein (15% [+Pro] or 5% [−Pro]), but adequate levels of all other nutrients for 4 wk to determine the effects of Se deficiency and protein deficiency on tissue Se and glutathione peroxidase (GSHPx) activity in rats. Plasma, heart, liver, and kidney Se and GSHPx were significantly lower in Se-deficient groups in relation to Se-sufficient groups. In Se-deficient groups, Se and GSHPx were significantly higher in −Se−Pro rats in heart, liver, and kidney. Data analysis showed that there were significant interaction effects between dietary Se and protein on Se and GSHPx of rats. It is assumed that under the condition of Se deficiency. a low level of protein may decrease Se and GSHPx utilization, increase GSHPx synthesis, and result in Se redistribution. This could account for high levels of Se and GSHPx in the −Se−Pro rats compared to −Se+Pro rats.     

Lead effect on the oxidation resistance of erythrocyte membrane in rat triton-induced hyperlipidemia

The anemia observed in severe chronic lead poisoning is in part attributable to alterations in the erythrocyte physicochemical properties. Since they are partly related to the membrane lipid composition, the aim of the present study was to determine the effects of a triton-induced hyperlipidemia on the resistance to oxidation of erythrocyte membranes in lead-treated Wistar rats. Our results showed that triton administration to lead-treated rats induced an increase in erythrocyte choline phospholipid levels together with a significant decrease in the erythrocyte membrane lipid resistance to oxidation. These results led us to suggest that anemia in lead poisoning is linked to interactions between lead present in the membrane and plasma phospholipids. Their increase in rat hyperlipidemia induced by triton resulted in a decrease in the membrane resistance to oxidation and finally in an erythrocyte fragility leading to their destruction.     

Methionine transamination—metabolic function and subcellular compartmentation

Enzymatic activities catalysing the inter-conversion of L-methionine and its oxy analogue 4-methylthio-2-oxobutyric acid (2,4-KMB) were detected in the liver, skeletal muscle and heart of the laboratory rat and of sheep. In both species the highest activity of methionine transamination was found in the liver and was located in the cytoplasm and mitochondria. We propose that physiological and nutritional role of the cytoplasmic methionine transamination is amination of 2,4 KMB and formation of L-methionine while in mitochondria the activity is responsible for disposal of excess methionine is oxidised through oxidative decarboxylation of 2,4 KMB.