Author(s):
The liver is vital to metabolic activities making it susceptible to liver injury. CCl4induced hepatotoxicity is widely studied in model organisms to assess liver damage as it directly mimics the damage in humans. CCl4 activation is ascribed to various cytochrome (CYP) 2E1, CYP2B1 or CYP2B2, and possibly CYP3A, resulting in the trichloromethyl radical, CCl3. This radical can bind to biological molecules (lipid, protein, nucleic acid) rendering the lipid metabolism non-functional and thus contribute to fatty degeneration. The formation of an adduct between DNA and CCl3 is considered as the initiator of hepatic carcinogenicity. CCl3 in presence of oxygen gave rise to far more reactive CCl3OO and initiate lipid peroxidation which ultimately leads to loss of membrane integrity.
At the molecular level, CCl4 mediate the release of several inflammatory cytokines (which may either be noxious or beneficial) among which TNF and NO appears to have a controversial role in CCl4 induced hepatotoxicity in that it can be either beneficial or detrimental. Such as among which TNF-α and NO accentuate the effect through cellular apoptosis and TGF-β contributes to fibro genesis. IL-6 and IL-10 are pivotal to a recovery process as it counteracts to minimize the anti-apoptotic activity and direct the cell towards regeneration. The intervention of any of the above-mentioned mechanistic aspects might aid in preventing more serious liver damage specifically employment of antioxidants, mutagenic agent, and maintenance of calcium sequestration. Moreover, CYP450 or the drugs preventing CCl4 induced cytotoxicity and proliferation would offer a protective response against hepatic cancer.
