The Role of AMPK Activation for Cardioprotection in Doxorubicin-Induced Cardiotoxicity

AbstractDoxorubicin is a commonly used chemotherapeutic agent for the treatment of a range of cancers, but despite its success in improving cancer survival rates, doxorubicin is cardiotoxic and can lead to congestive heart failure. Therapeutic options for this patient group are limited to standard heart failure medications with the only drug specific for doxorubicin cardiotoxicity to reach FDA approval being dexrazoxane, an iron-chelating agent targeting oxidative stress. However, dexrazoxane has failed to live up to its expectations from preclinical studies while also bringing up concerns about its safety. Despite decades of research, the molecular mechanisms of doxorubicin cardiotoxicity are still poorly understood and oxidative stress is no longer considered to be the sole evil. Mitochondrial impairment, increased apoptosis, dysregulated autophagy and increased fibrosis have also been shown to be crucial players in doxorubicin cardiotoxicity. These cellular processes are all linked by one highly conserved intracellular kinase: adenosine monophosphate –activated protein kinase (AMPK). AMPK regulates mitochondrial biogenesis via PGC1α signalling, increases oxidative mitochondrial metabolism, decreases apoptosis through inhibition of mTOR signalling, increases autophagy through ULK1 and decreases fibrosis through inhibition of TGFβ signalling. AMPK therefore sits at the control point of many mechanisms shown to be involved in doxorubicin cardiotoxicity and ca...
Source: Cardiovascular Drugs and Therapy - Category: Cardiology Source Type: research

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By WILLIAM H. BESTERMANN JR., MD New Scientific Breakthroughs Can Provide a Longer Healthier Life Twenty-one years of follow-up comparing usual care with a protocol-driven team-based intervention in diabetes proved that healthy life in humans can be prolonged by 8 years. These results were achieved at a lower per patient per year cost. Aging researchers have been confident that we will soon be able to prolong healthy life. This landmark study shows this ambitious goal can be achieved now with lifestyle intervention and a few highly effective proven medications. These medications interfere with the core molecular biol...
Source: The Health Care Blog - Category: Consumer Health News Authors: Tags: Medical Practice Patients aging chronic disease Denmark Diabetes William Bestermann Source Type: blogs
When Tom Shicowich’s toe started feeling numb in 2010, he brushed it off as a temporary ache. At the time, he didn’t have health insurance, so he put off going to the doctor. The toe became infected, and he got so sick that he stayed in bed for two days with what he assumed was the flu. When he finally saw a doctor, the physician immediately sent Shicowich to the emergency room. Several days later, surgeons amputated his toe, and he ended up spending a month in the hospital to recover. Shicowich lost his toe because of complications of Type 2 diabetes as he struggled to keep his blood sugar under control. He wa...
Source: TIME: Health - Category: Consumer Health News Authors: Tags: Uncategorized health Nutrition Source Type: news
Publication date: Available online 25 September 2018Source: Journal of EthnopharmacologyAuthor(s): Ching-Hui Huang, Hui-Ping Chang, Shou-Yi Su, Wen-Kang Chen, Yu-Jun Chang, Yang-Cheng Lee, Yu-Jui KuoAbstractEthnopharmacological relevanceCardiovascular disease is the main concern of breast cancer survivors who received doxorubicin treatment. Traditional Chinese medicine (TCM) provides as a complementary therapy to patients with breast cancer and is an important component of health care in Taiwan. However, the TCM utilization patterns and it's efficacy in breast cancer patients is unknown.Materials and methodsFrom a sample o...
Source: Journal of Ethnopharmacology - Category: Drugs & Pharmacology Source Type: research
This article is part of the European guidelines on perioperative venous thromboembolism prophylaxis. For details concerning background, methods, and members of the ESA VTE Guidelines Task Force, please, refer to: Samama CM, Afshari A, for the ESA VTE Guidelines Task Force. European guidelines on perioperative venous thromboembolism prophylaxis. Eur J Anaesthesiol 2018; 35:73–76. A synopsis of all recommendations can be found in the following accompanying article: Afshari A, Ageno W, Ahmed A, et al., for the ESA VTE Guidelines Task Force. European Guidelines on perioperative venous thromboembolism prophylaxis. Execu...
Source: European Journal of Anaesthesiology - Category: Anesthesiology Tags: Guidelines Source Type: research
CoQ10 has made the mainstream. You can find it everywhere. But the type of CoQ10 I want to tell you about has been completely ignored. That’s too bad, because this new form is 8 times better at getting into your blood and staying there. And that’s where it has its miracle-like anti-aging effects. This new form of CoQ10 may give you the opportunity to live disease-free for the rest of your life. Today, I’ll show you how this new “reduced” form of CoQ10 gives you greater power to prevent and reverse disease. You’ll also discover that it ramps up your energy levels and slows your aging proc...
Source: Al Sears, MD Natural Remedies - Category: Complementary Medicine Authors: Tags: Nutrition antioxidants CoQ10 ubiquinol Source Type: news
This article is part of the European guidelines on perioperative venous thromboembolism prophylaxis. For details concerning background, methods, and members of the ESA VTE Guidelines Task Force, please, refer to: Samama CM, Afshari A, for the ESA VTE Guidelines Task Force. European guidelines on perioperative venous thromboembolism prophylaxis. Eur J Anaesthesiol 2018; 35:73–76. A synopsis of all recommendations can be found in the following accompanying article: Afshari A, Ageno W, Ahmed A, et al., for the ESA VTE Guidelines Task Force. European Guidelines on perioperative venous thromboembolism prophylaxis. Execu...
Source: European Journal of Anaesthesiology - Category: Anesthesiology Tags: Guidelines Source Type: research
If you’ve been diagnosed with heart disease, the chances are you’ve been told to take low-dose aspirin every day as a preventative measure against heart attack and stroke. It’s most commonly prescribed for patients with congestive heart failure. This is the inability of your heart to pump as much blood as your body needs. And this is a big worry to me, because there is very little evidence that aspirin helps. In fact, regular use of aspirin — even baby aspirin — can do you more harm than good. Common Aspirin Beliefs The idea is that aspirin thins the blood, making it easier to pump.  It i...
Source: Al Sears, MD Natural Remedies - Category: Complementary Medicine Authors: Tags: Heart Health Source Type: news
Authors: Saha SP, Whayne TF Abstract Coenzyme Q-10 (CoQ10) is a widely used alternative medication or dietary supplement and one of its roles is as an antioxidant. It naturally functions as a coenzyme and component of oxidative phosphorylation in mitochondria. Decreased levels have been demonstrated in diseased myocardium and in Parkinson disease. Farnesyl pyrophosphate is a critical intermediate for CoQ10 synthesis and blockage of this step may be important in statin myopathy. Deficiency of CoQ10 also has been associated with encephalomyopathy, severe infantile multisystemic disease, cerebellar ataxia, nephrotic s...
Source: Southern Medical Journal - Category: Journals (General) Tags: South Med J Source Type: research
Abstract Lovastatin, the progenitor of the statin family, is in fact a naturally occurring compound produced by the yeast Monascus purpureus. Red yeast rice (RYR), a traditional Chinese food made by fermenting rice with M purpureus, is an herbal medicine that has been used for 1200 y as a therapy for problems related to circulation and digestion. RYR contains a range of compounds known as monacolins, of which monacolin K-renamed lovastatin by pharmaceutical researchers-was found to be the most potent inhibitor of cholesterol synthesis. Standardized extracts of RYR, providing 10 mg of monacolins daily, have been sh...
Source: Alternative Therapies in Health and Medicine - Category: Complementary Medicine Authors: Tags: Altern Ther Health Med Source Type: research
Conclusions: Among veterans, the majority of statins are prescribed for primary prevention. One in 5 veterans received a statin for an indication not supported by either guideline. These findings present an opportunity to reduce inefficient care.
Source: Circulation: Cardiovascular Quality and Outcomes - Category: Cardiology Authors: Tags: Session Title: Poster Session I Source Type: research
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