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.
Subject(s)
Antibiotics, Antineoplastic , Antioxidants/therapeutic use , Berberine/therapeutic use , Chemical and Drug Induced Liver Injury/drug therapy , Cytochrome P-450 Enzyme System/metabolism , Doxorubicin , Immunologic Factors/therapeutic use , Animals , Antioxidants/pharmacology , Berberine/pharmacology , Chemical and Drug Induced Liver Injury/immunology , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/pathology , Cytokines/blood , Immunologic Factors/pharmacology , Liver/drug effects , Liver/metabolism , Liver/pathology , Male , NF-kappa B/genetics , Rats, Wistar , Toll-Like Receptor 2/genetics , Toll-Like Receptor 4/geneticsABSTRACT
Previous reports have seldom concerned about the RTILs (Room temperature ionic liquids), and their effects on derivatization reaction or derivatives. In this study, we reported that the effects of four different RTILs, i.e., [EMIM]PF(6), [BMIM]PF(6), [HMIM]PF(6) and [OMIM]PF(6), on fluorescence spectra of 17 ß-estradiol (E2), and its derivatization solvent dansyl chloride (DNSCl) and the derivative. [BMIM]PF(6) had a significant quenching effect on the fluorescence intensity of E2, suggesting the formation of [BMIM]PF(6)/E2 complexes and possible buried E2 molecular in a more hydrophobic microenvironment. The estimated Stern-Volmer quenching constant (Ksv=0.3519) proved that E2 quenching caused by [BMIM]PF(6) was a dynamic quenching process. Four RTILs, with different alkyl chain-length in imidazolium cation, resulted in different quenching intensities to E2 as follows: [EMIM]PF(6) > [BMIM]PF(6) > [HMIM]PF(6) > [OMIM]PF(6). At 5 mg L(-1) of DNSCl, [BMIM]PF(6), [HMIM]PF(6) and [OMIM]PF(6) increased the fluorescence intensities of E2 in water by 8.5, 7.6 and 6.1 times, respectively, and a 37-nm hypsochromic shift occurred. The fluorescence intensity for [BMIM]PF(6)-extracted derivative of E2 increased more than two times compared with that for the control. In conclusion, this study demonstrated that above four hexafluorophosphate salt ionic liquids could be used in derivatization reaction to enhance fluorescent sensitivity in E2 trace residual analysis.
