Enalapril prevents fatty liver in nephrotic rats

A number of clinical entities, including nephrotic syndrome, present light to moderate enlargement of the liver due to accumulation of neutral fats (triglycerides) in the hepatocytes. Even though the outcome of hepatic steatosis does not seem to be harmful, when an additional inflammatory component is present, a variable degree of hepatic fibrosis and chronic liver disease could occur. In the last few years, ACE inhibitors have demonstrated multifunctional properties beyond their hemodynamic effects, especially as anti-inflammatory modulators and anti-oxidative stress agents. The purpose of the present study was to evaluate the possible protective action of an ACE inhibitor, enalapril (E), on fatty liver in adriamicyn-induced nephrotic rats (NR).

Two-month-old male Sprague-Dawley rats were separated into four groups. Control Group (G1, n = 18), N Group (G2, n = 18); NR + E Group (G3, n = 18), E Group (G4, n = 18). To induce an experimental model of nephrot ic syndrome, G2 and G3 received a single injection of adriamycin (7.5mg/kg b.w.) I.V. For twelve weeks, G3 and G4 received E daily at a concentration of 20 mg/L in their drinking water. At the end of the study, liver lesions were evaluated using standard staining. In order to detect fat in the liver and identify activated hepatic stellate cells (HSCs), inflammatory cell infiltration and amount of hepatic TGFI1, Oil red O and monoclonal antibodies (anti-a-smooth muscle actin, anti-monocytes/macrophages and anti-TGFbeta1) were used respectively. Hepatic lesions were quantified by semiquantitative scores. Creatinine clearance, urinary albumin excretion, serum lipids and liver enzymes were also studied to evaluate renal and liver function.

Although having the same serum lipid levels, G3 rats (NR + E) when compared with the nephrotic rats of G2 showed: 1) fewer liver lesions: a) fatty liver (% hepatocytes with fatty deposits): 36.6 +/- 11.4 vs. 4.2 +/- 4.9; p < 0.01; b) hepatic necrosis score: 1.22 +/- 0.42 vs. 0.13 +/- 0.28; p< 0.01; c) ED1 (monocytes/macrophages) score: 1.33 +/- 0.48 vs. 0.30 +/- 0.30; p < 0.01; d) HSCs score: 1.02 +/- 0.26 vs. 0.08 +/- 0.19; p < 0.01; e) liver interstitial TGFbeta1 score 0.75 +/- 0.5 vs. 0.08 +/- 0.19; p < 0.01; p < 0.01; f) liver fibrosis score: 1.11 +/- 0.32 vs. 0.08 +/- 0.19; p < 0.01; 2) lower serum liver enzymes: a) SGOT: 581.7 +/- 91.1 UI/L vs. 303.3 +/- 46.2 UI/L; p < 0.05; b) SGPT: 170.7 +/- 31.1 UI/L vs. 81 +/- 15.8 U.I./L; p < 0.05. Rats from G2 (NR) showed a positive and significant correlation between serum cholesterol and serum triglycerides and % fatty liver (r = 0.72 p 0.01 and r = 0.77 p < 0.01 respectively). This relation was not found in animals in G3 (NR+E).

In the present study enalapril showed a significant protective effect on hepatic steatosis and its inflammatory reaction. These data suggest that enalapril treatment in nephrotic syndrome, beyond its specific antiproteinuric and renoprotective effects, could provide additional liver protection.