{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T12:29:46Z","timestamp":1766492986208,"version":"3.41.2"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,8,11]],"date-time":"2020-08-11T00:00:00Z","timestamp":1597104000000},"content-version":"vor","delay-in-days":223,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science Fund of Medical University \u201cProf. Dr. Paraskev Stoyanov,\u201d"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:p><jats:italic>Doxorubicin<\/jats:italic> 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\u2010threatening adverse effects, such as cardio\u2010 and nephrotoxicities. Nonetheless, simultaneous administration of <jats:italic>doxorubicin<\/jats:italic> and antioxidants, such as those found in <jats:italic>green tea<\/jats:italic> leaves, could reduce cardiac and renal tissue damage caused by oxidative stress. The methylxanthine fraction isolated from <jats:italic>Bancha tea<\/jats:italic> leaves were tested <jats:italic>in vitro<\/jats:italic> for its antioxidant activity and <jats:italic>in vivo<\/jats:italic> for its organoprotective properties against <jats:italic>doxorubicin<\/jats:italic>\u2010induced cardio\u2010 and nephrotoxicities in a rat model. The <jats:italic>in vivo<\/jats:italic> study was conducted on male Wistar rats divided into 6 groups. Methylxanthines were administered at high (5\u2009mg\/kg body weight) and low (1\u2009mg\/kg body weight) doses, while doxorubicin was administered at a cumulative dose of 20\u2009mg\/kg body weight. Serum creatinine, uric acid, and urea concentrations, as well as serum enzyme levels (creatinine kinase (CK), creatinine kinase MB fraction (CK\u2010MB), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH)) and electrolytes (Na<jats:sup>+<\/jats:sup>, K<jats:sup>+<\/jats:sup>, and Cl<jats:sup>-<\/jats:sup>), were analysed. In addition, histological analysis was performed to assess cardiac and renal tissue damage. The concomitant administration of <jats:italic>Bancha<\/jats:italic> methylxanthines and <jats:italic>doxorubicin<\/jats:italic> showed a dose\u2010dependent 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\u2009mg\/kg resulted in an almost normal myocardial structure and a significant decrease in the morphological kidney changes caused by <jats:italic>doxorubicin<\/jats:italic> exposure compared with the group that received <jats:italic>doxorubicin<\/jats:italic> alone. The putative mechanism is most likely related to a reduction in the oxidative stress caused by doxorubicin.<\/jats:p>","DOI":"10.1155\/2020\/4018412","type":"journal-article","created":{"date-parts":[[2020,8,11]],"date-time":"2020-08-11T23:51:35Z","timestamp":1597189895000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Protective Effect of Methylxanthine Fractions Isolated from <i>Bancha<\/i> Tea Leaves against Doxorubicin\u2010Induced Cardio\u2010 and Nephrotoxicities in Rats"],"prefix":"10.1155","volume":"2020","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5778-4043","authenticated-orcid":false,"given":"Maya P.","family":"Radeva-Ilieva","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1839-1452","authenticated-orcid":false,"given":"Kaloyan D.","family":"Georgiev","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8760-8654","authenticated-orcid":false,"given":"Nadezhda R.","family":"Hvarchanova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0528-0289","authenticated-orcid":false,"given":"Stanila S.","family":"Stoeva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6678-2461","authenticated-orcid":false,"given":"Iliya J.","family":"Slavov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0731-3937","authenticated-orcid":false,"given":"Deyan L.","family":"Dzhenkov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7893-8822","authenticated-orcid":false,"given":"Marieta P.","family":"Georgieva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,8,11]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0b013e32833ffb56"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11912-018-0696-8"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1002151"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-017-3413-7"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.04.033"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1159\/000480471"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.09.171"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40360-017-0184-z"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.00635"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/bcr2756"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13649"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.3390\/foods6120109"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-50468-7"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0023-6438(95)80008-5"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/165457"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(98)00315-3"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.3390\/antiox2040230"},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/jf0710985"},{"key":"e_1_2_10_19_2","doi-asserted-by":"publisher","DOI":"10.18203\/2319-2003.ijbcp20194254"},{"key":"e_1_2_10_20_2","doi-asserted-by":"publisher","DOI":"10.14748\/ssp.v1i1.605"},{"key":"e_1_2_10_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13791"},{"key":"e_1_2_10_22_2","first-page":"439","article-title":"Electrolyte and morphologic alterations of myocardium in adriamycin-treated rabbits","volume":"77","author":"Olson H. 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