Previous studies demonstrated methane generation in aerobic cells. Our aims were to investigate the methanogenic features of sodium azide (NaN(3))-induced chemical hypoxia in the whole animal and to study the effects of l-α-glycerylphosphorylcholine (GPC) on endogenous methane production and inflammatory events as indicators of a NaN(3)-elicited mitochondrial dysfunction. Group 1 of Sprague-Dawley rats served as the sham-operated control; in group 2, the animals were treated with NaN(3) (14 mg·kg(-1)·day(-1) sc) for 8 days. In group 3, the chronic NaN(3) administration was supplemented with daily oral GPC treatment. Group 4 served as an oral antibiotic-treated control (rifaximin, 10 mg·kg(-1)·day(-1)) targeting the intestinal bacterial flora, while group 5 received this antibiotic in parallel with NaN(3) treatment. The whole body methane production of the rats was measured by means of a newly developed method based on photoacoustic spectroscopy, the microcirculation of the liver was observed by intravital videomicroscopy, and structural changes were assessed via in vivo fluorescent confocal laser-scanning microscopy. NaN(3) administration induced a significant inflammatory reaction and methane generation independently of the methanogenic flora. After 8 days, the hepatic microcirculation was disturbed and the ATP content was decreased, without major structural damage. Methane generation, the hepatic microcirculatory changes, and the increased tissue myeloperoxidase and xanthine oxidoreductase activities were reduced by GPC treatment. In conclusion, the results suggest that methane production in mammals is connected with hypoxic events associated with a mitochondrial dysfunction. GPC is protective against the inflammatory consequences of a hypoxic reaction that might involve cellular or mitochondrial methane generation.

NOX4 activation is a decisive component in the IR-induced microcirculatory dysfunction. Exogenous GPC ameliorates the inflammatory activation, and preserves the postischemic microvascular perfusion and liver functions, these effects being associated with a reduced hepatic expression of NOX4.

Alzheimer's disease (AD) is the most common form of dementia in the elderly. For more effective therapy early diagnostic markers could be beneficial. Therefore we compared one year old rats with adults and examined if changes in possible brain markers of AD preceeded memory decline. We also tested if vasopressin-deficient animals were useful model of AD as vasopressin has well known positive effect on memory and AD patient has decreased vasopressin production.We compared adult (3 month) and old (12 month), normal and vasopressin-deficient Brattleboro rats. To receive a comprehensive picture about their memory we examined their social discrimination, object discrimination and conditioned learning abilities (shuttle box).Amyloid precursor protein (APP), mitogen-activated protein kinase 1 (MAPK1), β-actin and tryptophan 2,3-dioxygenase 2 (TDO2) mRNA levels was measured by quantitative PCR.There was no difference between the memory of adult and aged groups. The vasopressin-deficient rats at both ages showed a weaker performance in the course of social and object discrimination tests and a higher escape failure during the shuttle box experiment. The brain marker mRNAs of the elder animals were higher than the levels of the adults, but the absence of vasopressin had no influence on them.Thus, the one year old rats showed elevated levels of AD-related markers, but memory deficits were observable only in vasopressin deficient animals. Vasopressin does not seem to have pathogenic role in AD. Changes in the studied markers might predict later symptoms, although further studies are required for confirmation.

This model permits for the first time to explore the microvascular processes in the mandibular periosteum after chronic ZOL treatment. This approach may contribute to a better understanding of the pathomechanism and the development of strategies to counteract bisphosphonate-induced side effects.

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Remote IPC limited the IR-induced microcirculatory dysfunction, but the protective effect did not affect all NOX homologs (at least not NOX4). The residual damage and inflammatory activation could well be linked to the unchanging NOX4 activity.