Doxorubicin (DOX) is an efficient
antineoplastic agent with a broad antitumor spectrum; however,
doxorubicin-associated cardiotoxic adverse effect through oxidative damage and apoptosis limits its clinical application.
Cafestol (Caf) is a naturally occurring
diterpene in unfiltered
coffee with unique
antioxidant, antimutagenic, and anti-inflammatory activities by activating the Nrf2 pathway. The present study aimed to investigate the potential chemoprotective effect of
cafestol on DOX-induced
cardiotoxicity in rats. Wistar albino rats of both sexes were administered
cafestol (5 mg/kg/day) for 14 consecutive days by oral gavage alone or with
doxorubicin which was injected as a single dose (15 mg/kg intraperitoneally at day 14) to induce toxicity. The result showed that Caf significantly improved cardiac injury induced by
doxorubicin, decreased serum levels of CK-MB, LDH, ALP, and ALT, and improved histopathological changes. In addition,
cafestol significantly inhibited DOX-induced cardiac oxidative stress as seen in the reduced level of MDA and increased GSH, SOD, CAT, and Gpx-1 cardiac tissue levels;
cafestol significantly enhanced Nrf2 gene and
protein expression and promoted the expression of downstream
antioxidant genes HO-1 and NQO-1 and downregulated Keap1 and NF-κB genes' expression; in addition, Caf significantly reduced inflammatory mediators, TNF-α, and IL-1β levels and inhibited cardiac apoptosis by modulating Bax and Casp 3 tissue levels and reduced TUNEL-positive cardiomyocytes. In conclusion, the present study confirmed that
cafestol improved the cardiotoxic effects induced by
doxorubicin through the regulation of apoptosis and oxidative stress response through the Nrf2 pathway; this study suggests that
cafestol may serve as a potential adjuvant in
chemotherapy to alleviate DOX-induced toxicities.