title: Protective mechanisms of coenzyme-Q10 may involve up-regulation of testicular P-glycoprotein in doxorubicin-induced toxicity.
abstract: The anticancer drug; doxorubicin (DOX), causes testicular toxicity as an adverse effect. P-glycoprotein (P-gp) is a multidrug resistance efflux transporter expressed in blood-testis barrier, which extrudes DOX from the testis. We investigated whether DOX-induced gonadal injury could be prevented by the use of antioxidant; coenzyme-Q10 (CoQ10). The involvement of P-gp expression, as a possible protective mechanism, was also investigated. CoQ10 was administered orally for 8 days, and DOX toxicity was induced via a single i.p. dose of 15 mg/kg at day 4. Concomitant administration of CoQ10 with DOX significantly restored testicular oxidative stress parameters and the distorted histopathological picture, reduced the up-regulation of caspase 3 caused by DOX, and increased P-gp expression. We show for the first time that CoQ10 up-regulates P-gp as a novel mechanism for gonadal protection. In conclusion, CoQ10 protects against DOX-induced testicular toxicity in rats via ameliorating oxidative stress, reducing apoptosis and up-regulating testicular P-gp.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia, Egypt.
authors.forename: Azza A K
authors.initials: AA
authors.lastname: El-Sheikh
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia, Egypt. Electronic address: mamm222@hotmail.com.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Morsy
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia, Egypt.
authors.forename: Marwa M
authors.initials: MM
authors.lastname: Mahmoud
authors.affiliation: Department of Histology, Faculty of Medicine, Minia University, El-Minia, Egypt.
authors.forename: Rehab A
authors.initials: RA
authors.lastname: Rifaai
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D004317:Doxorubicin / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D017208:Rats, Wistar; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D009566:Nitrates; D009573:Nitrites; D020011:Protective Agents; D014451:Ubiquinone; D008315:Malondialdehyde; D004317:Doxorubicin; D002374:Catalase; C024989:coenzyme Q10; D005978:Glutathione
keywords: Coenzyme-Q10; Doxorubicin; P-glycoprotein; Testicular toxicity