Key result
Creatine supplementation combined with exercise attenuated doxorubicin-induced hepatic inflammation, oxidative stress, morphological alterations, and fibrosis in mice.
Why the study?
The study tested whether creatine supplementation potentiates the protective effects of exercise against doxorubicin-induced hepatotoxicity.
Does creatine supplementation combined with exercise prevent doxorubicin-induced hepatotoxicity in mice?
RCT (n=38)
randomly allocated
Does creatine supplementation combined with exercise prevent doxorubicin-induced hepatotoxicity in mice?
Creatine supplementation potentiates the protective effects of exercise against doxorubicin-induced hepatotoxicity in a mouse model.
Does not support clinical use in doxorubicin-treated patients; leaves open translation of creatine-exercise synergy from mouse hepatoprotection models.
We tested the hypothesis that creatine supplementation may potentiate exercise’s protective effects against doxorubicin-induced hepatotoxicity. Thirty-eight Swiss mice were randomly allocated into five groups: control (C, n = 7), exercised (Ex, n = 7), treated with doxorubicin (Dox, n = 8), treated with doxorubicin and exercised (DoxEx, n = 8), and treated with doxorubicin, exercised, and supplemented with creatine (DoxExCr, n = 8). Doxorubicin was administered weekly (i.p.) for a total dose of 12 mg/kg. Creatine supplementation (2% added to the diet) and strength training (climbing stairs, 3 times a week) were performed for a total of 5 weeks. The results demonstrated that doxorubicin caused hepatotoxicity, which was evidenced by increased (p < 0.05) hepatic markers of inflammation (i.e., TNF-α and IL-6) and oxidative damage, while the redox status (GSH/GSSG) was reduced. The plasma concentrations of liver transaminases were also significantly (p < 0.05) elevated. Furthermore, doxorubicin-treated animals presented hepatic fibrosis and histopathological alterations such as cellular degeneration and the infiltration of interstitial inflammatory cells. Exercise alone partly prevented doxorubicin-induced hepatotoxicity; thus, when combined with creatine supplementation, exercise was able to attenuate inflammation and oxidative stress, morphological alterations, and fibrosis. In conclusion, creatine supplementation potentiates the protective effects of exercise against doxorubicin-induced hepatotoxicity in mice.
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Godinho et al. (2023) conducted an RCT in Doxorubicin-induced hepatotoxicity (n=38). Creatine supplementation and exercise vs. Control, exercise alone, doxorubicin alone, and doxorubicin plus exercise was evaluated on Hepatotoxicity (hepatic markers of inflammation, oxidative damage, redox status, and liver transaminases). Creatine supplementation combined with exercise attenuated doxorubicin-induced hepatic inflammation, oxidative stress, morphological alterations, and fibrosis in mice.
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