Antifibrotic action of telmisartan in experimental carbon tetrachloride-induced liver fibrosis in Wistar rats.
OBJECTIVE
Liver fibrosis is the increasingly accumulation of extracellular matrix (ECM), caused by chronic liver injuries, and represents a difficult clinical challenge in the entire world. Currently, the advanced knowledge of the cellular and molecular mechanisms of liver fibrosis showed that collagen-producing cells, like activated hepatic stellate cells (HSCs), portal fibroblasts and myofibroblasts are activated by fibrogenic cytokines, such as angiotensin II, transforming growth factor-beta 1 (TGF-β1), and leptin. Because of these, we tested telmisartan, an angiotensin II (AT1) receptor blocker and a peroxisome proliferator-activated receptor-γ (PPARγ) partial agonist, for investigate its antifibrotic action, on experimental model of carbon tetrachloride-induced liver fibrosis.


METHODS
In this research, we used two groups of Wistar rats, which received intraperitoneal (i.p.) injection of carbon tetrachloride (CCl4) 40% dissolved in olive oil, twice weekly for four consecutive weeks (initial dose of 5 mL÷kg, and other doses 3 mL÷kg). After one week, one group was received by gavage telmisartan (TS) dissolved in saline 0.9%, daily in dose of 8 mg÷kg, for 28 days. One group of Wistar rats was used for control. The antifibrotic action of telmisartan was investigated on the pathological changes of the liver and immunohistochemical analysis for hepatic stellate (Ito) cells (HSCs) reaction using anti-alpha-smooth muscle actin (anti α-SMA) antibody and macrophages cells (Kupffer cells) reaction using anti-CD68 antibody.


CONCLUSIONS
In group treated with telmisartan, hepatic fibrogenesis process was significantly reduced, in comparison with CCl4 group.
Department of Vegetal & Animal Biology, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, Romania; carmen2_bejenaru@yahoo.com.
Floriana Elvira
FE
Ionică
LaurenŢiu
L
Mogoantă
Gabriela Camelia
GC
Nicola
Cornel
C
ChiriŢă
Simona
S
Negreş
Cornelia
C
Bejenaru
Adriana
A
Turculeanu
Oana
O
Badea
Nicoleta Laura
NL
Popescu
Ludovic Everard
LE
Bejenaru
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D001565:Benzoates / Q000008:administration & dosage / Q000627:therapeutic use*; D002251:Carbon Tetrachloride / Q000009:adverse effects*; D005260:Female; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D000077333:Telmisartan
D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D002251:Carbon Tetrachloride; D000077333:Telmisartan