Abstract:While nano-sized construct (NSC) use in medicine has grown significantly in recent years, reported unwanted side effects have raised safety concerns. However, the toxicity of NSCs to the cardiovascular system (CVS) and the relative merits of the associated evaluation methods have not been thoroughly studied. This review discusses the toxicological profiles of selected NSCs and provides an overview of the assessment methods, including in silico, in vitro, ex vivo and in vivo models and how they are related to C… Show more
“… 87 HRV and BP variability have been used for the assessment of preclinical drug safety for drug-induced cardiotoxicity. 88 – 90 Figure 3. Spectrograms of heart rate variability (HRV) in cardiomyopathy induced by doxorubicin (right).…”
Sudden death is a major health problem all over the world. The most common causes of sudden death are cardiac but there are also other causes such as neurological conditions (stroke, epileptic attacks and brain trauma), drugs, catecholamine toxicity, etc. A common feature of all these diverse pathologies underlying sudden death is the imbalance of the autonomic nervous system control of the cardiovascular system. This paper reviews different pathologies underlying sudden death with emphasis on the autonomic nervous system contribution, possibilities of early diagnosis and prognosis of sudden death using various clinical markers including autonomic markers (heart rate variability and baroreflex sensitivity), present possibilities of management and promising prevention by electrical neuromodulation.
“… 87 HRV and BP variability have been used for the assessment of preclinical drug safety for drug-induced cardiotoxicity. 88 – 90 Figure 3. Spectrograms of heart rate variability (HRV) in cardiomyopathy induced by doxorubicin (right).…”
Sudden death is a major health problem all over the world. The most common causes of sudden death are cardiac but there are also other causes such as neurological conditions (stroke, epileptic attacks and brain trauma), drugs, catecholamine toxicity, etc. A common feature of all these diverse pathologies underlying sudden death is the imbalance of the autonomic nervous system control of the cardiovascular system. This paper reviews different pathologies underlying sudden death with emphasis on the autonomic nervous system contribution, possibilities of early diagnosis and prognosis of sudden death using various clinical markers including autonomic markers (heart rate variability and baroreflex sensitivity), present possibilities of management and promising prevention by electrical neuromodulation.
“…[ 23 ] PGA conjugation of an inhibitor of apoptotic protease activating factor 1 protected primary culture cardiomyocytes from hypoxia‐induced apoptosis, thanks to altered intracellular trafficking, [ 27 ] while altered whole‐body biodistribution improved outcomes in an in vivo model of acute kidney injury [ 28 ] and a kidney I/R injury rat model. [ 29 ] Given a demonstrated safety profile in the cardiovascular system [ 30 ] and an inherent potential to trigger therapeutic responses that act synergistically with conjugated factors, [ 31 ] we investigated PGA conjugation as a means to potentiate the therapeutic effects of PUFAs in the prevention of I/R injury. Among the available ω ‐3 derivatives, we selected di‐docosahexaenoic acid (diDHA) due to its reported cardioprotective activity [ 32 ] and the presence of adequate functionalities for PGA conjugation.…”
While coronary angioplasty represents an effective treatment option following acute myocardial infarction, the reperfusion of the occluded coronary artery can prompt ischemia–reperfusion (I/R) injury that significantly impacts patient outcomes. As ω‐3 polyunsaturated fatty acids (PUFAs) have proven, yet limited cardioprotective abilities, an optimized polymer‐conjugation approach is reported that improves PUFAs bioavailability to enhance cardioprotection and recovery in animal models of I/R‐induced injury. Poly‐l‐glutamic acid (PGA) conjugation improves the solubility and stability of di‐docosahexaenoic acid (diDHA) under physiological conditions and protects rat neonatal ventricular myocytes from I/R injury by reducing apoptosis, attenuating autophagy, inhibiting reactive oxygen species generation, and restoring mitochondrial membrane potential. Enhanced protective abilities are associated with optimized diDHA loading and evidence is provided for the inherent cardioprotective potential of PGA itself. Pretreatment with PGA–diDHA before reperfusion in a small animal I/R model provides for cardioprotection and limits area at risk (AAR). Furthermore, the preliminary findings suggest that PGA–diDHA administration in a swine I/R model may provide cardioprotection, limit edema and decrease AAR. Overall, the evaluation of PGA–diDHA in relevant preclinical models provides evidence for the potential of polymer‐conjugated PUFAs in the mitigation of I/R injury associated with coronary angioplasty.
“…The most prominent nanotoxicities include liver and kidney injury, lymphatic system and lung inflammation, and even fatality (Wu & Tang, ). Based on a large amount of in vitro and in vivo toxicity data from many types of biomaterials and inorganic materials (Cheah et al, ), it is believed that size is one of the origins of nanotoxicity (Hu, Sun, Kang, & Zhou, ; Li, Li, Yang, & Mei, ). Because NC particles are nano‐sized, it has been inferred that NCs still have some toxicity, though they may be better tolerated than other nanoparticles.…”
Nanocrystals (NCs), a type of innovative material particle, are a potential drug delivery platform that aims to improve the bioavailability of hydrophobic drugs. However, due to the lack of consideration of their toxicity, existing studies have not investigated whether the nanoscale properties of NCs, such as particle sizes, may lead to NC-induced toxicity. Because of the disparity between the rapid development of NCs and the lack of studies regarding NC toxicity, the present study investigated possible NC toxicity and clarified the relationship between particle sizes and NC toxicity. RAW264.7 and HepG2 cells were chosen as representatives of macrophage cells and tissue-type cells, respectively. Monosodium urate NCs were used as a drug model. Different particle sizes of monosodium urate NCs were prepared using precipitation methods. Methyl tetrazolium, lactate dehydrogenase, oxidative stress and apoptosis/necrosis assays were then used to evaluate cell damage and recovery. The results showed that small NC particle sizes produced higher toxicity than larger ones. In immune cells, these cytotoxic effects were greater than in tissue cells. After removal of small NCs, tissue cell damage could be significantly reversed, while immune cells were only slightly restored. However, after removal of large NCs, both cell types had almost no recovery. In summary, despite conventional wisdom, our research confirmed that NCs are not very safe and that NC particle sizes are closely related to the degree of NC toxicity.
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