Abstract
This study investigated the protective effects of carvedilol alone and coadministered with prednisolone and diltiazem on doxorubicin (DOX) and 5‐fluorouracil (5‐FU)‐induced toxicity. Each of 2 pools of 70 female rats were randomly allotted into 10 groups of 7 animals each and treated as follows: Group 1: normal saline (10 mL/kg); Group 2: normal saline and DOX (40 mg/kg)/5‐FU (20 mg/kg) alone; Group 3: gallic acid (200 mg/kg) and DOX/5‐FU; Group 4: carvedilol (0.075 mg/kg) and DOX/5‐FU; Group 5: carvedilol (0.15 mg/kg) and DOX/5‐FU; Group 6: carvedilol (0.30 mg/kg) and DOX/5‐FU; Group 7: diltiazem (3.43 mg/kg) and DOX/5‐FU; Group 8: diltiazem (3.43 mg/kg), carvedilol (0.15 mg/kg), and DOX/5‐FU; Group 9: prednisolone (0.57 mg/kg) and DOX/5‐FU; and Group 10: prednisolone (0.57 mg/kg), carvedilol (0.15 mg/kg), and DOX/5‐FU. Treatments were done p.o. for 16/14 days for the DOX/5‐FU models. DOX/5‐FU was administered i.p. to the rats in Groups 2‐10 on day 14/10‐14. On day 17/15 (DOX/5‐FU), blood samples were collected, and liver and kidneys of rats were harvested for antioxidant and histopathological assessments. Carvedilol alone and coadministered with prednisolone significantly (P < .05) decreased alanine aminotransferase level compared with administration of DOX alone. Carvedilol alone and coadministered with diltiazem significantly (P < .05) decreased creatinine level compared with administration of DOX/5‐FU alone. Carvedilol alone and coadministered with diltiazem and prednisolone significantly (P < .05) increased the level of hepatic superoxide dismutase and catalase, and decreased malondialdehyde compared with DOX administration alone. Histopathological observations correlated with results of biochemical and antioxidant analyses. Carvedilol administered alone and coadministered with diltiazem and prednisolone reduced the effect of DOX/5‐FU‐induced hepatic and renal toxicities due to enhanced in vivo antioxidant activity. The protective effect was more prominent in the doxorubicin model compared with the 5‐fluorouracil test. Coadministration of carvedilol with either diltiazem or prednisolone did not show better protection relative to carvedilol alone.
Highlights
Chemotherapy remains a strong indication for the treatment of cancer patients and antineoplastic agents like doxorubicin, 5-fluorouracil, and cisplatin are often used in the treatment of cancers
In respect of the 5-FU model, animals in Group 1 were administered normal saline (10 mL/kg) only for 14 days, while others were separately administered normal saline (Group 2); gallic acid (Group 3); carvedilol (Groups 4-6); diltiazem (Group 7); diltiazem and carvedilol (Group 8); prednisolone (Group 9); and prednisolone and carvedilol (Group 10) at the same doses used for the doxorubicin model for 14 days. 5-fluorouracil (20 mg/kg, i.p.) was administered to the rats in Groups 2-10 from days 10 to 14, 2 hours after treatment with the other drugs.[18]
The supratherapeutic dose of carvedilol in the presence of doxorubicin significantly increased the levels of hepatic superoxide dismutase (SOD) and CAT, and decreased MDA level compared with doxorubicin administration alone
Summary
Chemotherapy remains a strong indication for the treatment of cancer patients and antineoplastic agents like doxorubicin, 5-fluorouracil, and cisplatin are often used in the treatment of cancers. Doxorubicin is used to treat different forms of cancer, including ovarian, breast, lung, uterine and cervical cancers, Hodgkin’s disease, and soft tissue and primary bone sarcomas.[1]. The use of this drug is limited by toxic effects on body organs, causing cardiac, pulmonary, hepatic, renal, hematological, and testicular toxicities.2 5-Fluorouracil (5-FU), an antimetabolite, has played an important role in the management of colon and breast cancers, and cancers involving the head and neck.[3]. Most drug-induced nephrotoxicities exert toxic effects by one or more common pathological mechanisms, including altered intraglomerular hemodynamics, tubular cell toxicity, inflammation, crystal nephropathy, rhabdomyolysis, and thrombotic microangiopathy.[5]. This study aimed to determine the protective effect of carvedilol alone and coadministered with diltiazem and prednisolone against doxorubicin and 5-FU-induced liver and kidney toxicities
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
