Abstract
Background: The liver is one of the major organ involved in drug metabolism. Cytochrome P450s are predominantly involved in drug metabolism. A wide range of CYPs have been reported in the liver which have been involved in its normal as well as in diseased conditions. Doxorubicin, one of the most potent chemotherapeutic drugs, although highly efficacious, also has adverse side effects, with its targets being liver and cardiac tissue.
Objective: The study aims to evaluate the reversal potentials of berberine on Doxorubicin induced cyp conversion.
Methodology: In the present study, the interplay between anti-oxidants, cytochrome and inflammatory markers in DOX induced liver toxicity and its possible reversal by berberine was ascertained.
Results: DOX administration significantly elevated serum as well as tissue stress, which was reverted by berberine treatment. A similar response was observed in tissue inflammatory mediators as well as in serum cytokine levels. Most profound reduction in the cytochrome expression was found in Cyp 2B1, 2B2, and 2E1. However, 2C1, 2C6, and 3A1 although showed a decline, but it did not revert the expression back to control levels.
Conclusion: It could be concluded that berberine may be an efficient anti-oxidant and immune modulator. It possesses low to moderate cytochrome modulatory potentials.
Keywords: Chemotherapeutic agents, doxocubicin, berberine, Cyp, TLRs, inflammation.
Graphical Abstract
[PMID: 3597381]
[http://dx.doi.org/10.1056/NEJM198107163050305 ] [PMID: 7017406]
[PMID: 1462166]
[http://dx.doi.org/10.1007/BF00686550 ] [PMID: 7805179]
[http://dx.doi.org/10.1161/01.CIR.0000133187.74800.B9 ] [PMID: 15226229]
[http://dx.doi.org/10.1016/j.tox.2004.12.003 ] [PMID: 15725512]
[http://dx.doi.org/10.1007/BF02893506 ] [PMID: 17922055]
[http://dx.doi.org/10.1016/j.vph.2008.07.004 ] [PMID: 18707023]
[PMID: 31156784]
[http://dx.doi.org/10.1248/bpb.35.796 ] [PMID: 22687420]
[PMID: 4436300]
[PMID: 14938361]
[PMID: 4623845]
[http://dx.doi.org/10.2174/1872312810666160223121836 ] [PMID: 26902079]
[PMID: 14007123]
[http://dx.doi.org/10.1016/0005-2744(76)90110-8 ] [PMID: 974099]
[http://dx.doi.org/10.1016/0003-9861(59)90259-0]
[PMID: 4746326]
[http://dx.doi.org/10.2174/138920007781368863 ] [PMID: 17691916]
[http://dx.doi.org/10.1016/j.cbi.2006.12.011 ] [PMID: 17289008]
[http://dx.doi.org/10.2298/VSP110905041D ] [PMID: 23401928]
[http://dx.doi.org/10.4103/0971-6580.103656 ] [PMID: 23293460]
[http://dx.doi.org/10.1016/j.lfs.2018.03.023 ] [PMID: 29534993]
[http://dx.doi.org/10.3389/fphar.2019.01030 ] [PMID: 31572199]
[http://dx.doi.org/10.1152/ajpendo.00211.2007 ] [PMID: 17971514]
[http://dx.doi.org/10.2174/157016109788340659 ] [PMID: 19601857]
[http://dx.doi.org/10.2174/1573399810666140515112609 ] [PMID: 24828062]
[http://dx.doi.org/10.1038/nature07336 ] [PMID: 18806780]
[http://dx.doi.org/10.1016/j.tox.2009.12.018 ] [PMID: 20036707]
[http://dx.doi.org/10.1016/j.febslet.2007.01.044 ] [PMID: 17275817]
[http://dx.doi.org/10.1016/j.cbi.2012.01.006 ] [PMID: 22342832]