Cefadroxil potency as cancer co-therapy candidate by glutathione s-transferase mechanism

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.