title: Synergistic effects of irinotecan and flavonoids on Ehrlich ascites tumour-bearing mice.
abstract: Swiss albino mice were given Ehrlich ascites tumour cells (1 × 10(6)) intraperitoneally. For survival analysis and tumour growth analysis, the mice were administered quercetin and naringin (100 mg/kg) daily for 3 consecutive days, beginning on the third day after intraperitoneal (i.p.) injection of Ehrlich ascites tumour cells (1 × 10(6)). Irinotecan was administered ip at a dose of 50 mg/kg on days 1, 13 and 19. For the analysis of cell types and differential count of cells present in the peritoneal cavity, peripheral whole-blood leucocyte count and the comet assay, the mice were treated therapeutically with quercetin and naringin (100 mg/kg) and irinotecan (50 mg/kg) daily for 3 consecutive days beginning on third day after i.p. injection of Ehrlich ascites tumour cells (1 × 10(6)). We observed the synergistic anti-tumour effect expressed as the median survival time of mice treated with naringin in combination with irinotecan. All test components inhibited tumour growth and increased lifespan of mice except quercetin. The total number of cells present in the peritoneal cavity of mice significantly decreased in all treatments except quercetin. Single irinotecan and irinotecan combined with naringin had the highest DNA-damaging potential on peripheral blood leucocytes and lowest primary DNA damage, both in the kidney and liver cells as measured by the alkaline comet assay. Our results showed enhanced anti-tumour activity of irinotecan in combined treatment with flavonoids to reduce the deteriorating reaction of cytostatic drugs.
authors.affiliation: Department of Animal Physiology, Faculty of Science, University of Zagreb, Zagreb, Croatia.
authors.forename: Anica Horvat
authors.initials: AH
authors.lastname: Knežević
authors.forename: Domagoj
authors.initials: D
authors.lastname: Dikić
authors.forename: Duje
authors.initials: D
authors.lastname: Lisičić
authors.forename: Nevenka
authors.initials: N
authors.lastname: Kopjar
authors.forename: Nada
authors.initials: N
authors.lastname: Oršolić
authors.forename: Sanja
authors.initials: S
authors.lastname: Karabeg
authors.forename: Vesna
authors.initials: V
authors.lastname: Benković
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy*; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D044950:Flavanones / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D007274:Injections, Intraperitoneal; D000077146:Irinotecan; D007668:Kidney / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D010529:Peritoneal Cavity / Q000166:cytology / Q000473:pathology; D011794:Quercetin / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D044950:Flavanones; D000077146:Irinotecan; D011794:Quercetin; C005274:naringin; D002166:Camptothecin