Liver fibrosis in mice induced by carbon tetrachloride and its reversion by luteolin

Journal Article · Tue Dec 15 00:00:00 EST 2009 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2009.09.001· OSTI ID:21344814

Domitrovic, Robert ^[1]; Jakovac, Hrvoje ^[2]; Tomac, Jelena ^[3]; Sain, Ivana ^[4]

---

1. Department of Chemistry and Biochemistry, School of Medicine, University of Rijeka, B. Branchetta 20, 51000 Rijeka (Croatia)
2. Department of Physiology and Immunology, School of Medicine, University of Rijeka, Rijeka (Croatia)
3. Department of Histology and Embriology, School of Medicine, University of Rijeka, Rijeka (Croatia)
4. School of Medicine, University of Rijeka, Rijeka (Croatia)

Hepatic fibrosis is effusive wound healing process in which excessive connective tissue builds up in the liver. Because specific treatments to stop progressive fibrosis of the liver are not available, we have investigated the effects of luteolin on carbon tetrachloride (CCl{sub 4})-induced hepatic fibrosis. Male Balb/C mice were treated with CCl{sub 4} (0.4 ml/kg) intraperitoneally (i.p.), twice a week for 6 weeks. Luteolin was administered i.p. once daily for next 2 weeks, in doses of 10, 25, and 50 mg/kg of body weight. The CCl{sub 4} control group has been observed for spontaneous reversion of fibrosis. CCl{sub 4}-intoxication increased serum aminotransferase and alkaline phosphatase levels and disturbed hepatic antioxidative status. Most of these parameters were spontaneously normalized in the CCl{sub 4} control group, although the progression of liver fibrosis was observed histologically. Luteolin treatment has increased hepatic matrix metalloproteinase-9 levels and metallothionein (MT) I/II expression, eliminated fibrinous deposits and restored architecture of the liver in a dose-dependent manner. Concomitantly, the expression of glial fibrillary acidic protein and alpha-smooth muscle actin indicated deactivation of hepatic stellate cells. Our results suggest the therapeutic effects of luteolin on CCl{sub 4}-induced liver fibrosis by promoting extracellular matrix degradation in the fibrotic liver tissue and the strong enhancement of hepatic regenerative capability, with MTs as a critical mediator of liver regeneration.

• OSTI ID: 21344814
• Journal Information: Toxicology and Applied Pharmacology, Vol. 241, Issue 3; Other Information: DOI: 10.1016/j.taap.2009.09.001; PII: S0041-008X(09)00376-7; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ACTIN
ALKALINE PHOSPHATASE
CARBON TETRACHLORIDE
CONNECTIVE TISSUE
DOSES
FIBROSIS
HEALING
LIVER
METALLOTHIONEIN
MICE
MUSCLES
TOXICITY
ANIMAL TISSUES
ANIMALS
BIOLOGICAL RECOVERY
BODY
CHLORINATED ALIPHATIC HYDROCARBONS
DIGESTIVE SYSTEM
ENZYMES
ESTERASES
GLANDS
HALOGENATED ALIPHATIC HYDROCARBONS
HYDROLASES
MAMMALS
METALLOPROTEINS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
PHOSPHATASES
PROTEINS
RODENTS
VERTEBRATES