Zuzana Braunová

Metabolic Changes in Rat Brain After Prolonged Ethanol Consumption Measured by 1H and 31P MRS Experiments

AbstractSUMMARY 1. In vivo1H and 31P magnetic resonance spectroscopy techniques were applied to reveal biochemical changes in the rat brain caused by prolonged ethanol consumption.2. Three models of ethanol intoxication were used.3. 1H MRS showed a significant decrease in the concentration of myo-inositol in the brain of rats fed with 20% ethanol for 8 weeks. This change is consistent with perturbances in astrocytes. On the other hand, N-acetyl aspartate and choline content did not differ from controls.4. 31P MRS did not reveal any significant changes in the high-energy phosphates or intracellular free Mg2+ content in the brain of rats after 14 weeks of 20% ethanol drinking. The intracellular pH was diminished.5. By means of a 31P saturation transfer technique, a significant decrease was observed for the pseudo first-order rate constant kfor of the creatine kinase reaction in the brain of rats administered 30% ethanol for 3 weeks using a gastric tube.6. The 1H MRS results may indicate that myo-inositol loss, reflecting a disorder in astrocytes, might be one of the first changes associated with alcoholism, which could be detected in the brain by means of in vivo1H MRS.7. The results from 31P MRS experiments suggest that alcoholism is associated with decreased brain energy metabolism.8. 31P saturation transfer, which provides insight into the turnover of high-energy phosphates, could be a more suitable technique for studying the brain energetics in chronic pathological states than conventional 31P MRS.

A study of creatine kinase reaction in rat brain under chronic pathological conditions-chronic ischemia and ethanol intoxication.

Creatine kinase reaction rates were measured by the magnetisation transfer technique in brains of healthy adult and aged rats and in rats with chronic cerebral ischemia and chronic ethanol intoxication. These measurements indicated that the rate constant of the creatine kinase reaction is significantly reduced in the case of severe chronic cerebral ischemia in aged rats. In the adult rats, during chronic ethanol intoxication after 3 weeks of administration of 3 ml of 30% ethanol once a day via a gastric tube, a significant decrease in the pseudo first-order rate constant k(for) of the creatine kinase reaction was also found. In contrast, mild chronic cerebral ischemia in adult rats produced an increase in the reaction rate 4 weeks after occlusion. At the same time, corresponding conventional phosphorus magnetic resonance spectra showed negligible changes in signal intensities.

Oxidative Stress and Plasma Concentrations of Coenzyme Q10, α-Tocopherol, and β-Carotene in Patients with a Mild to Moderate Decrease of Kidney Function

Accessible online at: www.karger.com/journals/nef Dear Sir, Oxidative stress (OS) and decreased function of the antioxidant system are apparent in dialysis patients [1] and even in ‘uremic patients’ during the predialysis phase [2, 3]. However, data on OS in predialysis patients with a just mild to moderate kidney function decrease are lacking. We have determined OS plasma concentrations of malondialdehyde (MDA), the parameter of lipid peroxidation, coenzyme Q10 (CoQ10), ·-tocopherol (·-TOC), and ß-carotene (ß-CAR) and performed standard kidney function tests in a group of 55 predialysis patients with mild (creatinine clearance 160 ml/min; n = 21), moderate (n = 25), and severe (creatinine clearance !25 ml/min; n = 9) glomerulonephritis or interstitial nephritis. The reference values were obtained from original procedures and previous studies of our group. The MDA plasma levels were increased even in a group with a mild decrease of the creatinine clearance (table 1), and no further significant MDA increase was apparent with further decreases of the creatinine clearance (r = –0.242, p = 0.078). On the other hand, the CoQ10 concentrations were decreased in patients with mildly decreased creatinine clearance, and no further decreases were apparent with further decreasing kidney function (r = 0.186, p = 0.179). A correlation was found between these two variables (r = 0.327, p = 0.018). The concentrations of ßCAR were in the normal range in patients with a mildly decreased creatinine clearance, but decreased with deteriorating kidney function (r = 0.320, p = 0.030). The ·-TOC plasma concentrations were slightly increased in patients with mildly decreased creatinine clearance, but increased further with the decreasing creatinine clearance (r = –0.364, p = 0.007). Thus, OS develops during the early phase of kidney disease (marker of OS: increased MDA levels). The changes of ·-TOC and ßCAR are opposite: while ·-TOC concentrations increase, ß-CAR concentrations decrease. This basic relationship could be modified by various factors: for instance, the highest values of MDA (p = 0.010) were found in 5 patients treated with prednisone combined with ciclosporin. It could be concluded that OS develops early in patients with kidney disease, probably with pathogenetic significance and the possibility of preventing the progression of kidney impairment. The significance of CoQ10 seems to be of outstanding interest.