Cefadroxil potency as cancer co-therapy candidate by glutathione s-transferase mechanism
- Author:
Tri Yuliani
;
Sudibyo Martono
;
Sansan Sukamdani Tjipto
;
Muhammad Yusuf Putroutomo
;
Irwan Desyanto Raharjo Indartono
- Publication Type:Journal Article
- Keywords:
GSTs, cefadroxil, specific substrates, in vivo,co-therapy
- From:International e-Journal of Science, Medicine and Education
2013;7(1):15-20
- CountryMalaysia
- Language:English
-
Abstract:
Background: Glutathione S-transferases (GSTs) have
an important role in the detoxification of electrophiles,
such as some anticancer drugs. Compounds with phenolic
and/or α,b-unsaturated carbonyl group have been known
as GSTs inhibitor in vitro. Cefadroxil in vitro decreased
GST-Pi activity but not GSTs in rat kidney cytosol.
GST inhibitor in a specific organ and of a specific class
is needed for safety in cancer chemotherapy. The study
aims to observe the effect of cefadroxil on GSTs in vivo
in rat kidney cytosol and then compare it to those seen
for liver, lung, and spleen in vivo.
Methods: Cefadroxil was given twice a day by
forcefeeding for five days. Rat kidney cytosol was then
prepared and its protein concentration was determined.
Cytosolic total GST, GST-Mu and GST-Pi activities
were monitored by a continuous spectrophotometric
method using the following substrates: 1-chloro,
2,4-dinitrobenzene (CDNB) (non-specific substrate),
1,2-dichloro-4-nitrobenzene (DCNB) for GST-Mu, and
ethacrynic acid (EA) for GST-Pi.
Results: The data showed that cefadroxil significantly
increased the activity of GSTs, GST-Mu, and GSTPi
in rat kidney cytosol (8.75%, 47.81%, and 6.67%
respectively).
Conclusion: Cefadroxil did not inhibit GSTs, GST-Mu,
and GST-Pi in rat kidney in vivo indicating that it does
not inhibit chemotherapy detoxification by GSTs, GSTMu,
and GST-Pi in normal kidney cells.
- Full text:W020151005527587611784.pdf
