3. DISCUSSION
There is an imperative need for novel drugs that are devoid of
hepatotoxicity. Animal models have been in use for several decades for
evaluating the safety, efficacy and validation of drugs. There are
several animal models which can be used to examine pathogenesis and
development of cirrhosis and assessment of hepatoprotective drugs. These
models are developed by using drugs, diet, chemicals and surgery. Each
animal model of hepatic cirrhosis has its importance in short-term or
long-term studies. Various marketed drugs lead to hepatotoxicity even
with long-term use or short-term exposure such as paracetamol,
nimesulide, isoniazid, methotrexate, and Carbamazepine (77). Hence, to
overcome the side effects like hepatotoxicity and hepatocarcinoma, there
is a need to develop new drugs which can be used as safe alternatives.
And animal models are necessary for assessment of these drugs. Although
much work has been done in the evaluation of hepatoprotective drugs but
still bioengineering and extracellular matrix studies are in limelight
to evaluate their pathology, an inflammatory mediator involved, and
pathway progression (104). 2D monocultures, co-cultures, 3D spheroids
and organ-on-a-chip models are the advanced techniques employed in the
study of cellular responses mediated via pathophysiological phenomenon
in fibrosis development (105). The human stellate cells, adult stem
cells, and non-parenchymal cells are used in the development of
cocultures and 3D spheroids for the study of hepatic fibrosis, cirrhosis
and hepatic carcinomas. (106). Ex-vivo tissue culture techniques also
aid in different stage evaluation of cirrhosis (107). In future, the
pathology of the individual patient could be studied by
decellularisation of liver and hepatic tissue bioengineering (108).