Tumor necrosis factor-alpha, interleukin-1beta and nitric oxide: induction of liver megamitochondria in prehepatic portal hypertensive rats.
It has been shown that portal hypertension in the rat causes microvesicular hepatocytic fatty infiltration. Formation of megamitochondria (MG) is one of the most prominent alterations in steatosis. Because nitric oxide (NO), tumor necrosis factor-alpha (TNFalpha), and interleukin-1beta (IL-1beta) impair mitochondrial function, these mediators have been studied in prehepatic portal hypertensive rats to verify their coexistence with MG and therefore with steatosis. Male Wistar rats were divided into two groups: a control group (n = 7) and a group with partial portal vein hgation (n = 19) at 6 weeks of evolution. TNFalpha and IL-1beta were quantified in liver by enzyme-linked immunosorbent assay, and NO was measured in the portal vein, suprahepatic inferior vena cava, and infrahepatic inferior vena cava by the Griess reaction. In portal hypertensive rats, the serum concentration of NO of hepatic origin increases (132.10 +/- 34.72 vs. 52.44 +/- 11.32 nmol/ml; p < 0.001), as do TNFalpha (2.02 +/- 0.20 vs. 1.12 +/- 0.43 micromol/mg protein) and IL-1beta (18.95 +/- 2.59 vs. 5.48 +/- 1.70 micromol/mg protein) (p = 0.005) in the liver. The most frequent hepatic histologic findings are the presence of MG (p < 0.001), steatosis, and hyperplasia. An increase in hepatic release of NO, TNFalpha and IL-1beta with MG formation is produced in rats with portal hypertension. Therefore these proinflammatory mediators and this morphologic mitochondrial alteration could both be involved in the etiopathogenesis of steatosis.
Prieto
Isabel
I
Servicio de Cirugía General, Hospital Virgen de la Luz, Cuenca, Spain.
Jiménez
Fulgencio
F
Aller
Maria-Angeles
MA
Nava
Maria-Paz
MP
Vara
Elena
E
Garcia
Cruz
C
Arias
Jaime
J
D000818:Animals; D005234:Fatty Liver / Q000209:etiology / Q000503:physiopathology*; D006975:Hypertension, Portal / Q000150:complications / Q000503:physiopathology*; D007375:Interleukin-1 / Q000032:analysis* / Q000502:physiology; D008297:Male; D008930:Mitochondria, Liver / Q000502:physiology*; D023421:Models, Animal; D009569:Nitric Oxide / Q000032:analysis* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis* / Q000502:physiology
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide