Evaluation of the spontaneous reversibility of carbon tetrachloride-induced liver cirrhosis in rabbits

Abstract

There is a general consensus that liver fibrosis in humans is potentially reversible, while scepticism prevails on the concept that cirrhosis can be truly reversed. The availability of suitable experimental models is fundamental for disease research. The experimental murine model of liver cirrhosis induced by carbon tetrachloride (CCl(4)) reproduces both the histological picture of the postnecrotic cirrhosis and its biochemical and clinical parameters. Normal hepatic structure is modified by formation of regeneration nodules. Fibrosis represents a morphological element of disease and an effect of hepatocyte necrosis. However, the relevance for research of this well-established model of liver cirrhosis is hampered by some spontaneous cirrhosis regression reported in mice and rats. It has been reported that CCl(4) also induces experimental liver cirrhosis in rabbits, but it is not known whether the process is reversible in this species. The aim of our study was to investigate this question. Male New Zealand White rabbits were treated intragastrically with CCl(4) or the vehicle only for 19 weeks and groups were sacrificed three and five months after treatment interruption. Cirrhotic and control livers were processed for routine light microscopy and for morphometric study of fibrosis by semiquantitative evaluation. The degree of fibrosis was based on the Knodell's scoring system.

Assessment of liver fibrosis by ultrasound elastography and contrast-enhanced ultrasound: a randomized prospective animal study

“…A mortality rate of about 16.7% (10/60) was observed during the process of CCl 4 treatment. A mortality rate of 0% to 60% has been reported before [ 5 , 12 , 16 , 25 ].…”

“…CCl 4 injection is a conventional and widely used approach to induce liver fibrosis in experimental animals. According to published data [ 5 , 12 , 16 , 27 ], it took about 8–16 weeks to build liver cirrhosis in rabbits/dogs/pigs/rats. And the dose was about 0.1–0.3 ml/kg of 40–60% CCl 4 oil mixture, twice a week, assisted by phenobarbital or alcohol drinks and/or high-fat and low-protein diet.…”

Preventative effects of prostaglandin E1 in combination with iodized olive oil on liver fibrosis after transcatheter arterial chemoembolization in a rabbit model of CCl4-induced liver fibrosis

“…Further, the liver volume and blood volume are relatively large in rabbits, which makes them easy to operate on and suitable for researching interventional treatment (Bravo et al 2012), which is why rabbits were used to generate the model of liver fibrosis used in this study. The results showed that the body mass in the rabbit model of liver fibrosis had a tendency to decline, which could be due to the effects of CCl 4 on the rabbit's appetite.…”

Adenoviral-bone morphogenetic protein-7 and/or doxazosin therapies promote the reversion of fibrosis/cirrhosis in a cirrhotic hamster model

“…Spontaneous reversion of the liver cirrhosis after cessation of the CCl4-induction has been well documented ( 38 – 40 ). We observed spontaneous improvement in the fibrotic process and liver function in animals from Placebo group.…”