The aim of this study was to investigate the effect of oral administration of branched-chain amino acid (BCAA)-enriched diets after portacaval shunt (PCS) in rats. Fifty-one Sprague-Dawley male rats (200 gm) underwent PCS and 55 a sham operation. Half of the animals received BCAA 142 mg per day through a gastric tube; the other half underwent a sham procedure. Sleep disturbances were evaluated at 7, 14, and 28 days postoperatively by measurement of the excitability of the reticular brain-stem formation during the slow-wave sleep and paradoxical sleep. Animals were killed at the same intervals and liver/body weight ratio, plasma, and brain amino acids, brain norepinephrine, brain serotonin, 5-hydroxyindolacetic acid and histamine were measured. Each group of animals was matched with a similar group of sham-operated rats, i.e., receiving or not receiving BCAA. After PCS (as compared to sham-operated animals) a significant hyperexcitability of the reticular brain-stem formation was found during the slow-wave sleep. The liver/body weight ratio was significantly lower. Tryptophan (free tryptophan in the plasma), phenylalanine, tyrosine, and histidine increased in the plasma and the brain. Leucine and isoleucine were decreased in the plasma. After PCS, an initial decrease at 7 days postoperatively of brain norepinephrine and blockade of the intracerebral metabolism of tryptophan were observed. These changes were transient and progressively disappeared at 14 and 28 days postoperatively. Brain histamine remained at a very high level through the experiment. A good correlation was demonstrated between modification of the sleep disturbance and tryptophan (or 5- hydroxyindolacetic acid) and histamine brain levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Experimental acute liver ischemia in pigs induces an increment in plasma free tryptophan with decreased total tryptophan. Brain tryptophan is elevated in all brain areas. A slight, but significant increase of brain serotonin is demonstrated in the striatum only, while 5-HIAA (5-hydroxyindoleacetic acid) is significantly lower in the hypothalamus. Other brain areas do not show significant changes in serotonin and 5-HIAA levels. Neither the high plasma free tryptophan levels, nor the decreased sum of neutral competitive amino acids are consistent with such an elevation of brain tryptophan. Hemodialysis was carried out with two different kinds of membranes: cuprophan (with an efficient removal of molecules up to molecular weight 1300) and AN 69 polyacrylonitrile (efficient removal up to 15,000). Ammonia and aminoacid clearance are similar for both membranes. After AN 69, plasmatic free tryptophan and brain tryptophan are lower than after liver devascularization, but still higher than normal. Serotonin significantly increases in the cortex, midbrain and hypothalamus without concomitant rise of 5-HIAA levels. After cuprophan hemodialysis, plasma total tryptophan is lower than in normal and even comatose animals, whereas free tryptophan is normal. Intracerebral tryptophan is similar to AN 69 dialysed animals, but in the hypothalamus it is similar to nondialysed animals. Brain serotonin levels are not modified. 5-HIAA decreases in the hypothalamus. This finding suggests that middle molecules (which are not cleared out with cuprophan hemodialysis) are involved in the intracerebral transfer of tryptophan and the metabolism of serotonin, mainly in the hypothalamus.
Ammonia, amino acids (AA), and middle molecules (MM) have been implicated in the pathogenesis of experimentally induced acute hepatic coma in the pig. Hemodialysis (HD) using either a low- (Cuprophan = CU) or a high-permeability (polyacrylonitrile = AN 69) membrane has demonstrated the role of MM. Selective hemodialysis (SHD) of AA or NH3 and MM was performed by adding either NH3 (group I) or AA (group II) to the dialysate during AN 69 HD; for MM, SHD only was performed by adding NH3 and AA to the dialysate (group III). In group I the brain levels of tyrosine were similar to those in undialyzed animals with decreased striatal dopamine and decreased norepinephrine in the midbrain only. Brain tryptophan was higher than normal, but brain levels of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid (5-HT, 5-HIAA) were within normal limits. In group II, despite an efficient NH3 clearance, brain NH3 levels were as high as in group I and did not correlate with plasma levels. Brain tyrosine (despite tyrosine overload of the dialysate) was lower than in group I; striatal dopamine decreased (but to a lesser extent than in group I), and norepinephrine was normal. Brain tryptophan was higher than normal, with an increase in brain 5-HT and 5-HIAA. In group III, results were similar to group I, except for a limited increase of 5-HT in the pons. Brain octopamine levels increased only in undialyzed and CU-HD animals, demonstrating a specific relation with MM. These experiments demonstrate the interrelationship between NH3 and neutral AA with regard to passage through the blood-brain barrier and to intracerebral metabolism.
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