Spontaneously hypertensive rats exhibit increased liver flavin monooxygenase expression and elevated plasma TMAO levels compared to normotensive and Ang II-dependent hypertensive rats

Background: Flavin monooxygenases (FMOs) are enzymes responsible for the oxidation of a broad spectrum of exogenous and endogenous amines. There is increasing evidence that trimethylamine (TMA), a compound produced by gut bacteria and also recognized as an industrial pollutant, contributes to cardiovascular diseases. FMOs convert TMA into trimethylamine oxide (TMAO), which is an emerging marker of cardiovascular risk. This study hypothesized that blood pressure phenotypes in rats might be associated with variations in the expression of FMOs.Methods: The expression of FMO1, FMO3, and FMO5 was evaluated in the kidneys, liver, lungs, small intestine, and large intestine of normotensive male Wistar-Kyoto rats (WKY) and two distinct hypertensive rat models: spontaneously hypertensive rats (SHRs) and WKY rats with angiotensin II-induced hypertension (WKY-ANG). Plasma concentrations of TMA and TMAO were measured at baseline and after intravenous administration of TMA using liquid chromatography-mass spectrometry (LC-MS).Results: We found that the expression of FMOs in WKY, SHR, and WKY-ANG rats was in the descending order of FMO3 > FMO1 >> FMO5. The highest expression of FMOs was observed in the liver. Notably, SHRs exhibited a significantly elevated expression of FMO3 in the liver compared to WKY and WKY-ANG rats. Additionally, the plasma TMAO/TMA ratio was significantly higher in SHRs than in WKY rats.Conclusion: SHRs demonstrate enhanced expression of FMO3 and a higher plasma TMAO/TMA ratio. The variability in the expression of FMOs and the metabolism of amines might contribute to the hypertensive phenotype observed in SHRs

Evaluation of butyric acid as a potential supportive treatment in anterior uveitis

Background: The aim of the study was to evaluate the anti-inflammatory effect of topically administered aqueous sodium butyrate solution in an endotoxin-induced uveitis rat model and compare the results with corticosteroid treatment. Material and methods: Forty female Lewis rats were randomly divided into five groups. Uveitis was induced by a single lipopolysaccharide (LPS) injection into each footpad of each LPS+ rat. Group I (naive) received saline injected into the footpad of each rat at a dose of 0.1 mL/each footpad; Group II (LPS+) received saline solution topically. Group III (LPS+ Dex) — an aqueous dexamethasone sodium phosphate solution topically; Group IV (LPS+ But 0.5 mM) — 0.5 mM aqueous sodium butyrate solution topically, Group V (LPS+ But 1 mM) — 1.0 mM aqueous sodium butyrate solution topically. Clinical scoring of inflammation in rat eyes was evaluated before LPS injection and after 24 hours. The iris involvement, posterior synechiae presence, and insight into the eye fundus were clinicallyassessed. A histopathological examination was also performed. The rats were euthanatized 24 hours after LPS injection, and aqueous humor (AqH) was collected from the eyes by anterior chamber puncture. Levels of inflammatory cytokines and chemokines in the AqH were determined with commercially available Luminex assays. Results: Development of iris hyperemia associated with miosis and poor visibility of fundus details occurred 24 hours after LPS injection. Compared to the LPS+ group, the clinical scores were strongly suppressed in rats treated with Dexamethasone and moderately diminished in LPS+ But 0.5 mM. These clinical features were not observed in the controls (Group 1 — naive). Data from inflammatory cytokines evaluation indicates no significant differences between the LPS+ group (Group 2) and the LPS+ But groups (Groups 4 and 5). Histopathological examinations suggest that hyperemia, corneal stratification, and lesions were less common in the group of animals treated with BA in a lower concentration. Conclusion: Topical administration of sodium butyrate as a therapeutic agent might alleviate the severity of intraocular inflammation in eyes with uveitis. The effect of sodium butyrate was slight but clinically significant in 0.5 mM dose, so other doses of topically administered sodium butyrate should be considered and evaluated in further research

Trimethylamine, a gut bacteria metabolite and air pollutant, increases blood pressure and markers of kidney damage including proteinuria and KIM-1 in rats

BACKGROUND: Trimethylamine oxide (TMAO) is a biomarker in cardiovascular and renal diseases. TMAO originates from the oxidation of trimethylamine (TMA), a product of gut microbiota and manufacturing industries-derived pollutant, by flavin monooxygenases (FMOs). The effect of chronic exposure to TMA on cardiovascular and renal systems is undetermined. METHODS: Metabolic, hemodynamic, echocardiographic, biochemical and histopathological evaluations were performed in 12-week-old male SPRD rats receiving water (controls) or TMA (200 or 500 µM/day) in water for 18 weeks. TMA and TMAO levels, the expression of FMOs and renin-angiotensin system (RAS) genes were evaluated in various tissues. RESULTS: In comparison to controls, rats receiving high dose of TMA had significantly increased arterial systolic blood pressure (126.3 ± 11.4 vs 151.2 ± 19.9 mmHg; P = 0.01), urine protein to creatinine ratio (1.6 (1.5; 2.8) vs 3.4 (3.3; 4.2); P = 0.01), urine KIM-1 levels (2338.3 ± 732.0 vs. 3519.0 ± 953.0 pg/mL; P = 0.01), and hypertrophy of the tunica media of arteries and arterioles (36.61 ± 0.15 vs 45.05 ± 2.90 µm, P = 0.001 and 18.44 ± 0.62 vs 23.79 ± 2.60 µm, P = 0.006; respectively). Mild degeneration of renal bodies with glomerulosclerosis was also observed. There was no significant difference between the three groups in body weight, water-electrolyte balance, echocardiographic parameters and RAS expression. TMA groups had marginally increased 24 h TMA urine excretion, whereas serum levels and 24 h TMAO urine excretion were increased up to 24-fold, and significantly increased TMAO levels in the liver, kidneys and heart. TMA groups had lower FMOs expression in the kidneys. CONCLUSIONS: Chronic exposure to TMA increases blood pressure and increases markers of kidney damage, including proteinuria and KIM-1. TMA is rapidly oxidized to TMAO in rats, which may limit the toxic effects of TMA on other organs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-022-03687-y

DataSheet1_Spontaneously hypertensive rats exhibit increased liver flavin monooxygenase expression and elevated plasma TMAO levels compared to normotensive and Ang II-dependent hypertensive rats.DOCX

Background: Flavin monooxygenases (FMOs) are enzymes responsible for the oxidation of a broad spectrum of exogenous and endogenous amines. There is increasing evidence that trimethylamine (TMA), a compound produced by gut bacteria and also recognized as an industrial pollutant, contributes to cardiovascular diseases. FMOs convert TMA into trimethylamine oxide (TMAO), which is an emerging marker of cardiovascular risk. This study hypothesized that blood pressure phenotypes in rats might be associated with variations in the expression of FMOs.Methods: The expression of FMO1, FMO3, and FMO5 was evaluated in the kidneys, liver, lungs, small intestine, and large intestine of normotensive male Wistar-Kyoto rats (WKY) and two distinct hypertensive rat models: spontaneously hypertensive rats (SHRs) and WKY rats with angiotensin II-induced hypertension (WKY-ANG). Plasma concentrations of TMA and TMAO were measured at baseline and after intravenous administration of TMA using liquid chromatography-mass spectrometry (LC-MS).Results: We found that the expression of FMOs in WKY, SHR, and WKY-ANG rats was in the descending order of FMO3 > FMO1 >> FMO5. The highest expression of FMOs was observed in the liver. Notably, SHRs exhibited a significantly elevated expression of FMO3 in the liver compared to WKY and WKY-ANG rats. Additionally, the plasma TMAO/TMA ratio was significantly higher in SHRs than in WKY rats.Conclusion: SHRs demonstrate enhanced expression of FMO3 and a higher plasma TMAO/TMA ratio. The variability in the expression of FMOs and the metabolism of amines might contribute to the hypertensive phenotype observed in SHRs.</p

Double-Needle Yamane Technique Using Flanged Haptics in Ocular Trauma—A Retrospective Survey of Visual Outcomes and Safety

To evaluate visual outcomes and safety of the double-needle technique using flanged haptics (Yamane technique) in patients with aphakia caused by ocular trauma at a trauma referral center. Retrospective: Consecutive interventional case series of 30 patients who underwent the Yamane technique due to posttraumatic aphakia. The double-needle technique using flanged haptics was combined with anterior vitrectomy (group A) in 14 patients, and with pars plana vitrectomy (PPV) (group B) due to retinal detachment, nucleus dislocation into the vitreous cavity, or intraocular lens (IOL) displacement in 16 patients. No intraoperative complications were noted. There was significant improvement in the visual acuity in both groups at the second postoperative visit. However, the visual acuity was significantly worse in the group treated with the Yamane technique combined with PPV. Silicone oil tamponade in PPV group was associated with worse visual acuity, whereas post lensectomy status was associated with poor visual function result in the anterior vitrectomy group. There was one case of slight IOL decentration and one retinal detachment during the postoperative follow-up period in the group with PPV. In this case series, the Yamane technique applied in traumatized eyes was found to be an efficacious and safe procedure. Combining the Yamane technique with PPV due to posterior segment ocular trauma was associated with worse functional results in the follow-up at three months. Further studies with longer follow-up evaluations are required to verify long-term complications