Key result
L-arginine improves cardiac function and reduces myocardial injury and fibrosis versus doxorubicin alone in rats.
Why the study?
Clinical use of doxorubicin is limited by cardiotoxicity, and safe, effective preventive strategies remain limited.
Does L-arginine prevent doxorubicin-induced cardiotoxicity in preclinical models?
Does L-arginine prevent doxorubicin-induced cardiotoxicity in preclinical models?
Answers are grounded in this paper and cite their sources.
L-arginine demonstrates cardioprotective effects against doxorubicin-induced cardiotoxicity in preclinical models by reducing fibrosis and inflammation via AMPKα2 activation.
Background The clinical use of doxorubicin (DOX), a widely used and effective antitumor drug, is limited by its cardiotoxicity. Currently, safe and effective strategies for preventing doxorubicin-induced cardiotoxicity (DIC) remain limited. Therefore, this study aimed to investigate the potential cardioprotective effects and possible underlying mechanisms of L-arginine (L-Arg) against DIC. Methods and Results To investigate the cardioprotective effects and underlying mechanisms of L-Arg, three complementary experimental models were used: male Sprague–Dawley rats (n = 6 per group), male AMPKα2 knockout (AMPKα2 KO) mice (n = 6 per group), and H9c2 cardiomyocytes. A DIC model was induced in rats by intraperitoneal injection of DOX (2.5 mg/kg/week) for 6 weeks. Serum nitric oxide (NO) and lactate dehydrogenase (LDH) levels were measured to assess oxidative stress and myocardial injury. Cardiac morphology, inflammation, and fibrosis were evaluated by histological staining and protein expression analyses, whereas miR-29b-3p expression was determined by RT-qPCR. AMPKα2-deficient models and miR-29b-3p gain- and loss-of-function models were used to investigate the underlying mechanisms. Compared with the DOX group, L-Arg significantly improved cardiac function and morphology, reduced oxidative stress, myocardial injury, inflammation, and fibrosis, and increased miR-29b-3p expression (all P < 0.05). Moreover, miR-29b-3p overexpression enhanced, whereas miR-29b-3p inhibition attenuated, the cardioprotective effects of L-Arg (all P < 0.05). These protective effects were also markedly attenuated by AMPKα2 deficiency (P < 0.05). Conclusions L-Arg alleviates DIC by improving cardiac function, reducing oxidative stress, inflammation, and fibrosis, and increasing miR-29b-3p expression. These cardioprotective effects are associated with AMPKα2 activation and enhanced miR-29b-3p expression.
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Zhu et al. (2026) studied Doxorubicin-induced cardiotoxicity. L-arginine vs. Doxorubicin alone was evaluated on Cardiac function, morphology, oxidative stress, myocardial injury, inflammation, and fibrosis (p=<0.05). L-arginine significantly improved cardiac function and reduced oxidative stress, myocardial injury, inflammation, and fibrosis compared to doxorubicin alone (all P < 0.05).
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