Effect of chronic renal failure with metabolic acidosis on alanine metabolism in isolated liver cells.

BACKGROUND & AIMS: Decreased ureagenesis and gluconeogenesis from alanine have been reported during chronic renal failure in rat. This study addressed the respective roles of plasma-membrane transport and intracellular metabolism in these abnormalities of alanine pathways. METHODS: In hepatocytes isolated from uremic and control rats, we investigated: (1) the influence of uremia on gluconeogenesis and ureagenesis during incubations with alanine; (2) the kinetics of alanine plasma-membrane transport; (3) the relationships between intracellular alanine concentrations and its metabolism. Plasma-membrane alanine transport was assessed after addition of alanine (2 mM) by measuring its intracellular accumulation from 0 to 10 min, in the presence of a transaminase inhibitor. Alanine metabolism was studied in perifused hepatocytes by measuring intracellular alanine concentration together with urea, glucose and lactate production in the presence of increasing concentrations of alanine (0-8 mM). RESULTS: Uremic rats showed decreased plasma bicarbonate. Uremia induced (P<0.05) a decrease in both gluconeogenesis (36%) and ureagenesis (22%). Alanine plasma-membrane transport decreased by 20% during uremia. During perifusions, uremia induced a 30-40% decrease in urea, glucose, and lactate production without modifying intracellular alanine concentration. CONCLUSIONS: In uremic rats with acidosis, hepatocyte alanine utilization was impaired at both plasma-membrane transport and intracellular transamination steps.

Isolated rat hepatocyte metabolism is affected by chronic renal failure.

Metabolic changes due to chronic renal failure (CRF) were studied in isolated liver cells. In 14 CRF and 14 sham-operated rats, liver cells were isolated by the Berry and Friend method and incubated with various substrates in order to study gluconeogenesis, ureagenesis, ketogenesis, oxygen consumption as well as cytosolic and mitochondrial adenine nucleotide content. CRF rat hepatocytes exhibited a 25% to 45% decrease in gluconeogenesis and ureagenesis (P < 0.05) from all the tested substrates (lactate plus pyruvate, fructose, glycerol, dihydroxyacetone, alanine and glutamine for gluconeogenesis and alanine, glutamine, ammonia and ammonia plus ornithine for ureagenesis), while endogenous rates were unaffected. CRF did not alter ketone body production (acetoacetate and beta-hydroxybutyrate) from oleate or octanoate. In the presence of either oleate, lactate plus pyruvate or ammonia, oxygen uptake as well as cytosolic and mitochondrial total adenine nucleotides were unaffected by CRF, while the mitochondrial ATP/ADP ratio decreased (P < 0.001). Thus, this study of hepatocyte intermediary metabolism during CRF showed an alteration of only gluconeogenesis and ureagenesis pathways. Moreover, the association of normal oxygen uptake together with decreased mitochondrial ATP/ADP ratio suggest a possible increase in hepatocyte ATP demand during uremia.

Splanchnic acid-base status and urea metabolism in uremic rats.

Acidosis may alter hepato-splanchnic amino acid metabolism during uremia.26 uremic rats and 30 controls were studied for portal and arterial acid-base balance and urea synthesis during enteral nutrition. Uremic rats exhibited increased (p < 0.05) portal H(+) (47.20 +/- 0.018 vs 43.05 +/- 0.49 nmol/I) and decreased HCO(3)(-) (19.45 +/- 0.69 vs 23.01 +/- 0.57 mmol/l) without significant change in arterial H(+) (45.29 +/- 1.13 vs 43.15 +/- 0.49) and HCO(3)(-) (18.41 +/- 0.64 vs 19.59 +/- 0.49). Porto-arterial difference showed an intestinal HCO(3)(-) release in controls only (3.53 +/- 0.64 mmol/l). Urea synthesis rate was significantly enhanced by enteral nutrition in controls only: 54.33 +/- 17.3 vs -11.8 +/- 20 micromol/min 100g body mass. Thus, during uremia, portal acidosis was associated with a decrease in enteral nutrition-induced urea synthesis.

Plants in the traditional medicine of the Ubaye Valley.

The study of the traditional pharmacopoeia in the Ubaye Valley (in the Alpes de Haute Provence department) enabled us to draw up a table showing 136 medicinal plants, their vernacular names, their suitable parts, the instructions for use, the medical purposes and the principal pharmacological and therapeutical properties. This study points out the close connection between plants, pathology and the living conditions of an agro-sylvo-pastoral civilization.