Abstract P326: Trimethylamine, A Gut Bacteria Metabolite And Air Pollutant, Increases Blood Pressure, Proteinuria And Markers Of Kidney Damage In Rats.

Abstract

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 industry-derived pollutant, by flavin monooxygenases (FMOs). The effect of chronic exposure to TMA on cardiovascular and renal systems is undetermined. Metabolic, hemodynamic, echocardiographic, biochemical and histopathological evaluations were performed in male, 12-week-old rats receiving water (control group) or TMA (500 μM/day) in water for 18 weeks (each group: n=9). TMA and TMAO levels, the expression of FMOs and RAS genes were evaluated in various tissues. Data are expressed as the median (Q1; Q3) or mean ± SE. In comparison to controls, rats receiving TMA had significantly increased systolic blood pressure (mmHg; 151.2 ± 7.0 vs. 126.3 ± 3.8; P<0.05), urine protein to creatinine ratio [3.4 (3.3; 4.2) vs. 1.6 (1.5; 2.8); P<0.05], urine KIM-1 levels (pg/ml; 3 519.0 ± 301.6 vs. 2 338.3 ± 244.0; P<0.05), mild degeneration of renal bodies with glomerulosclerosis, and hypertrophy of the tunica media of arteries and arterioles. There was no significant difference between the groups in body weight, water-electrolyte balance and echocardiographic parameters and RAS expression. TMA group had marginally increased 24hr TMA urine excretion [μM; 5.0 (3.8; 5.5) vs. 0.3 (0.2; 0.4); P<0.01]. However, TMA serum level [μM/l; 0.32 (0.27; 0.64) vs. 0.04 (0.03; 0.04)], TMAO serum level [49.5 (45.8; 84.8) vs. 9.0 (6.5; 11.9)] and 24hr TMAO urine excretion [255.4 (237.2; 311.1) vs. 10.6 (10.3; 11.2); all P<0.001] were increased. TMA group had lower FMOs expression in the kidneys but significantly increased TMAO levels in the liver [μM/kg; 35.9 (29.3; 41.9) vs. 5.4 (4.2; 9.6)], renal cortex [189.7 (82.2; 204.5) vs. 14.5 (13.1; 21.9)], renal medulla [192.0 (74.0; 213.7) vs. 18.5 (14.4; 27.8)] and heart [96.3 (90.3; 112.4) vs. 3.2 (2.4; 5.8); all P<0.001]. In conclusion, 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 toxic effects of TMA.