Abstract
Doxorubicin is an anthracycline antibiotic that is used for the treatment of various types of cancer. However, its clinical usage is limited due to its potential life-threatening adverse effects, such as cardio- and nephrotoxicities. Nonetheless, simultaneous administration of doxorubicin and antioxidants, such as those found in green tea leaves, could reduce cardiac and renal tissue damage caused by oxidative stress. The methylxanthine fraction isolated from Bancha tea leaves were tested in vitro for its antioxidant activity and in vivo for its organoprotective properties against doxorubicin-induced cardio- and nephrotoxicities in a rat model. The in vivo study was conducted on male Wistar rats divided into 6 groups. Methylxanthines were administered at high (5 mg/kg body weight) and low (1 mg/kg body weight) doses, while doxorubicin was administered at a cumulative dose of 20 mg/kg body weight. Serum creatinine, uric acid, and urea concentrations, as well as serum enzyme levels (creatinine kinase (CK), creatinine kinase MB fraction (CK-MB), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH)) and electrolytes (Na+, K+, and Cl−), were analysed. In addition, histological analysis was performed to assess cardiac and renal tissue damage. The concomitant administration of Bancha methylxanthines and doxorubicin showed a dose-dependent reduction in the serum biochemical parameters, indicating a decrease in the cardiac and renal tissue damage caused by the antibiotic. Histological analysis showed that pretreatment with methylxanthines at the dose of 5 mg/kg resulted in an almost normal myocardial structure and a significant decrease in the morphological kidney changes caused by doxorubicin exposure compared with the group that received doxorubicin alone. The putative mechanism is most likely related to a reduction in the oxidative stress caused by doxorubicin.
Highlights
Doxorubicin is an anthracycline antibiotic that is used for the treatment of a variety of cancer diseases, such as Hodgkin’s and non-Hodgkin’s lymphoma, multiple myeloma, and breast, lung, and ovarian tumours
Antioxidant Activity of the Methylxanthine Fraction Isolated from Bancha Tea Leaves
In our previous study, high-performance liquid chromatography (HPLC) analysis of the methylxanthine fraction showed 88.11% caffeine, 0.42% theobromine, and no theophylline content [13], whereby our assumptions were made that the properties of this fraction would be similar to that of caffeine, and this could be used for amelioration of doxorubicininduced oxidative stress
Summary
Doxorubicin is an anthracycline antibiotic that is used for the treatment of a variety of cancer diseases, such as Hodgkin’s and non-Hodgkin’s lymphoma, multiple myeloma, and breast, lung, and ovarian tumours. This antibiotic is often combined with other chemotherapeutic drugs. Two major mechanisms have been proposed for the antitumour activity of doxorubicin. Topoisomerase II is an essential enzyme for DNA replication, which relaxes DNA supercoils. This results in an inhibition of macromolecule biosynthesis in tumour cells. The other mechanism of action of doxorubicin is due to the formation of free radicals. Reductive conversion of doxorubicin into a semiquinone radical is essential for the cytotoxic
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