Role of mitochondria in doxorubicin-mediated cardiotoxicity: from molecular mechanisms to therapeutic strategies.

This comprehensive review delves into the pivotal role of mitochondria in doxorubicin-induced cardiotoxicity, a significant complication limiting the clinical use of this potent anthracycline chemotherapeutic agent. Doxorubicin, while effective against various malignancies, is associated with dose-dependent cardiotoxicity, potentially leading to irreversible cardiac damage. The review meticulously dissects the molecular mechanisms underpinning this cardiotoxicity, particularly focusing on mitochondrial dysfunction, a central player in this adverse effect. Central to the discussion is the concept of mitochondrial quality control (MQC), including mitochondrial dynamics (fusion/fission balance) and mitophagy. The review presents evidence linking aberrations in these processes to cardiotoxicity in doxorubicin-treated patients. It elucidates how doxorubicin disrupts mitochondrial dynamics, leading to an imbalance between mitochondrial fission and fusion, and impairs mitophagy, culminating in the accumulation of dysfunctional mitochondria and subsequent cardiac cell damage. Furthermore, the review explores emerging therapeutic strategies targeting mitochondrial dysfunction. It highlights the potential of modulating mitochondrial dynamics and enhancing mitophagy to mitigate doxorubicin-induced cardiac damage. These strategies include pharmacological interventions with mitochondrial fission inhibitors, fusion promoters, and agents that modulate mitophagy. The review underscores the promising results from preclinical studies while advocating for more extensive clinical trials to validate these approaches in human patients. In conclusion, this review offers valuable insights into the intricate relationship between mitochondrial dysfunction and doxorubicin-mediated cardiotoxicity. It underscores the need for continued research into targeted mitochondrial therapies as a means to improve the cardiac safety profile of doxorubicin, thereby enhancing the overall treatment outcomes for cancer patients.

Bu-Shen-Jian-Pi-Yi-Qi Therapy Prevents Alcohol-Induced Osteoporosis in Rats.

Bu-Shen-Jian-Pi-Yi-Qi therapy, which refers to reinforcing kidney, regulating qi, and invigorating spleen, is a traditional Chinese medicine, and we investigated its efficacy in treatment of alcohol-induced osteoporosis and its underlying mechanism. Forty adult male Sprague-Dawley rats were randomly assigned into alcohol-supplemented group, JIAN-GU-LING (JGL) group, calcium D3 + alfacalcidol group, and sham-treated group. Bone mineral density (BMD), bone mineral content (BMC), and bone biomechanical properties were assessed. Biochemical analyses of serum and urine specimens were detected. Reverse transcription-polymerase chain reaction was used to detect the mRNA level of vitamin D receptor (VDR). There were markedly lower bone metabolic markers and biomechanical properties in alcohol-supplemented group compared with sham-treated group (all P < 0.05). BMD, BMC, 25(OH)D3, and 1,25(OH)2D3 were elevated in JGL group relative to calcium D3 + alfacalcidol group (all P < 0.05). U-Ca/Cr and U-P/Cr in JGL group were higher than those in the calcium D3 + alfacalcidol group (all P < 0.05). VDR mRNA level in the JGL group was elevated markedly in comparison with alcohol + calcium D3 + alfacalcidol group (P < 0.05). Based on our results, Bu-Shen-Jian-Pi-Yi-Qi therapy inhibits bone loss, promotes bone formation, and effectively improves bone metabolism in rats with experimental alcoholic osteoporosis. The disease reversal is evidenced by increased BMD and BMC, improved biomechanical properties, elevated VDR mRNA level, enhanced response sensitivity of 1, 25(OH)2D3, and reduced S-Ca/P.

Role of mitochondria in doxorubicin-mediated cardiotoxicity: From molecular mechanisms to therapeutic strategies.

This comprehensive review delves into the pivotal role of mitochondria in doxorubicin-induced cardiotoxicity, a significant complication limiting the clinical use of this potent anthracycline chemotherapeutic agent. Doxorubicin, while effective against various malignancies, is associated with dose-dependent cardiotoxicity, potentially leading to irreversible cardiac damage. The review meticulously dissects the molecular mechanisms underpinning this cardiotoxicity, particularly focusing on mitochondrial dysfunction, a central player in this adverse effect. Central to the discussion is the concept of mitochondrial quality control, including mitochondrial dynamics (fusion/fission balance) and mitophagy. The review presents evidence linking aberrations in these processes to cardiotoxicity in doxorubicin-treated patients. It elucidates how doxorubicin disrupts mitochondrial dynamics, leading to an imbalance between mitochondrial fission and fusion, and impairs mitophagy, culminating in the accumulation of dysfunctional mitochondria and subsequent cardiac cell damage. Furthermore, the review explores emerging therapeutic strategies targeting mitochondrial dysfunction. It highlights the potential of modulating mitochondrial dynamics and enhancing mitophagy to mitigate doxorubicin-induced cardiac damage. These strategies include pharmacological interventions with mitochondrial fission inhibitors, fusion promoters, and agents that modulate mitophagy. The review underscores the promising results from preclinical studies while advocating for more extensive clinical trials to validate these approaches in human patients. In conclusion, this review offers valuable insights into the intricate relationship between mitochondrial dysfunction and doxorubicin-mediated cardiotoxicity. It underscores the need for continued research into targeted mitochondrial therapies as a means to improve the cardiac safety profile of doxorubicin, thereby enhancing the overall treatment outcomes for cancer patients.