Protective effects of propolis and related polyphenolic/flavonoid compounds against toxicity induced by irinotecan.
Despite the excellent chemotherapeutic effect of irinotecan, its cytotoxicity and genotoxicity in normal cells remains a major problem in chemotherapy. This study was carried out to find whether propolis preparations and related flavonoids (quercetin, naringin) might enhance irinotecan-induced cytotoxicity to tumor cells in mice bearing Ehrlich ascites tumors (EAT) while protecting normal blood, liver, and kidney cells. The preparation of propolis and their flavonoids were given to mice intraperitoneally at a dose of 100 mg kg(-1) body weight for three consecutive days before the ip injection of EAT cells (2×10(6)). Irinotecan was administered ip at dose of 50 mg kg(-1) on days 3, 4, and 5 after tumor cell inoculation. The combination treatment resulted in substantial inhibition of the growth of EAT cells as well as treatment with quercetin or irinotecan alone, whereas other treatment by itself showed little effect. However, when mice were pre-treated with test components prior to irinotecan, the frequencies of irinotecan-induced micronuclei (MN) was decreased but in mice bearing tumor QU and EEP increased number of micronucleated cells. Propolis preparation and related flavonoids were found to exhibit an important immunomodulatory effect and could decrease irinotecan-induced toxic and genotoxic effects to normal cells without effecting irinotecan cytotoxicity in EAT cells.
Oršolić
Nada
N
Department of Animal Physiology, Faculty of Science, University of Zagreb, Rooseveltov trg 6, Zagreb, 10000, Croatia. norsolic@yahoo.com
Benković
Vesna
V
Lisičić
Duje
D
Dikić
Domagoj
D
Erhardt
Julija
J
Knežević
Anica Horvat
AH
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D001773:Blood Cells; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000633:toxicity; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D002478:Cells, Cultured; D005419:Flavonoids / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D000077146:Irinotecan; D007668:Kidney / Q000166:cytology / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D010636:Phenols / Q000627:therapeutic use*; D011429:Propolis / Q000627:therapeutic use*
D000972:Antineoplastic Agents, Phytogenic; D005419:Flavonoids; D007155:Immunologic Factors; D010636:Phenols; D000077146:Irinotecan; D011429:Propolis; D002166:Camptothecin