Hypertensive rats show increased renal excretion and decreased tissue concentrations of glycine betaine, a protective osmolyte with diuretic properties.

Hypertension leads to water-electrolyte disturbances and end-organ damage. Betaine is an osmolyte protecting cells against electrolyte imbalance and osmotic stress, particularly in the kidneys. This study aimed to evaluate tissue levels and hemodynamic and renal effects of betaine in normotensive and hypertensive rats. Betaine levels were assessed using high-performance liquid chromatography-mass spectrometry (HPLC-MS) in normotensive rats (Wistar-Kyoto, WKYs) and Spontaneously Hypertensive rats (SHRs), a model of genetic hypertension. Acute effects of IV betaine on blood pressure, heart rate, and minute diuresis were evaluated. Gene and protein expression of chosen kidney betaine transporters (SLC6a12 and SLC6a20) were assessed using real-time PCR and Western blot. Compared to normotensive rats, SHRs showed significantly lower concentration of betaine in blood serum, the lungs, liver, and renal medulla. These changes were associated with higher urinary excretion of betaine in SHRs (0.20 ± 0.04 vs. 0.09 ± 0.02 mg/ 24h/ 100g b.w., p = 0.036). In acute experiments, betaine increased diuresis without significantly affecting arterial blood pressure. The diuretic response was greater in SHRs than in WKYs. There were no significant differences in renal expression of betaine transporters between WKYs and SHRs. Increased renal excretion of betaine contributes to decreased concentration of the protective osmolyte in tissues of hypertensive rats. These findings pave the way for studies evaluating a causal relation between depleted betaine and hypertensive organ damage, including kidney injury.

Mice, Rats and Guinea Pigs Exhibit Significant Variations in the Plasma, Urine and Tissue Levels of Taurine, Betaine, Sarcosine and Other Osmolyte-Active Amino Acids.

BACKGROUND: Osmolytes are naturally occurring compounds that protect cells from osmotic stress in high-osmolarity tissues, such as the kidney medulla. Some amino acids, including taurine, betaine, glycine, alanine, and sarcosine, are known to act as osmolytes. This study aimed to establish the levels of these amino acids in body fluids and tissues of laboratory animals used as models for human diseases in biomedical research. METHODS: Liquid chromatography coupled with mass spectrometry was used to quantify taurine, glycine, betaine, alanine, beta-alanine, and sarcosine in plasma, urine, and tissues of adult, male mice, rats and guinea pigs. RESULTS: Among the species analyzed, taurine was found to have the highest tissue concentrations across all compounds, with the heart containing the greatest amount. In guinea pigs, betaine levels were higher in the renal medulla than in the renal cortex (p < 0.01), while in rats and mice, there were no significant differences in betaine levels between the kidney cortex and medulla. The urine of guinea pigs had lower levels of sarcosine compared to rats (p < 0.001), while the plasma (p < 0.05; > 0.05), heart (p < 0.05; < 0.05), lungs (p < 0.01; < 0.01), liver (p < 0.001; < 0.05), and kidneys (p < 0.01; < 0.01) of rats exhibited notably higher concentrations of sarcosine compared to both mice and guinea pigs, respectively. CONCLUSIONS: There are pronounced differences in the concentrations of taurine, betaine, and other amino acids across the investigated species. It is important to acknowledge these differences when selecting animal models for preclinical studies and to account for variations in amino acid concentrations when selecting amino acids doses for interventional studies.

Hydrogen sulfide formation in experimental model of acute pancreatitis.

Acute pancreatitis (AP) is a disease defined as acute or chronic inflammatory process of the pancreas characterized by premature activation of digestive enzymes within the pancreatic acinar cells and causing pancreatic auto-digestion. In mammalian tissues, H2S is synthesized endogenously from L-cysteine in regulated enzymatic pathways catalyzed by pyridoxal phosphate-dependent enzymes: cystathionine beta - synthase (CBS), gamma - cystathionase (CTH) and cysteine aminotransferase (CAT) coupled with 3-mercaptopyruvate sulfurtransferase (MPST). In the mitochondria, hydrogen sulfide is oxidized to sulfite, which is then converted to thiosulfate (sulfane sulfur-containing compound) by thiosulfate sulfurtransferase (rhodanese; TST). The activity and the expression of CBS, CTH, MPST, and TST have been determined in vivo in pancreas of control rats, rats with acute pancreatitis and sham group. Levels of low-molecular sulfur compounds such as reduced and oxidized glutathione, cysteine, cystine and cystathionine were also determined. The study showed the significant role of MPST in H2S metabolism in pancreas. Stress caused by the surgery (sham group) and AP cause a decrease in H2S production associated with a decrease of MPST activity and expression. Markedly higher level of cysteine in the AP pancreas may be caused by a reduced rate of cysteine consumption in reaction catalyzed by MPST but it can also be a sign of the processes of proteolysis occurring in the changed tissue.