Heat Stress Nephropathy: What Have We Learned?

The unbearable heat waves that we are experiencing these days around the world are the result of increasing global warming, leading to heat stress and a constant health issue for the existing population. The thermoregulatory dysfunction of the human body due to climatological changes might result in fluid and electrolyte imbalance and transforms the human body from a normal physiological condition to a distorted pathological state. Subsequently, at one point in time, the human body may fail to handle its normal thermoregulatory function in the form of sudden unconsciousness and health defects. There might be associated dehydration that imposes renal damage, even to the extent to cause acute kidney injury (AKI), followed by chronic kidney disease (CKD). Thus, we cannot deny CKD as a major cause of death, mainly in patients having long-standing medical issues such as cardiac dysfunction, hypertension, diabetes, and obesity, heat stress nephropathy (HSN) might therefore become a major health problem. There is always a hopeful way in our hands, fortunately, which is of course prevention, that comes through government policies and human awareness. The present review brings out light on the alarming resultant facts of heat stress, dehydration, its pathology, molecular derangements, and recommendations for the prevention of heat stress nephropathy.

Therapeutic approaches of nutraceuticals in the prevention of Alzheimer's disease.

Alzheimer's disease (AD) is a neurological illness that causes memory loss over time. Currently, available pharmaceutical medicines and products are limited, and they have side effects at a higher price. Researchers and scientists have observed significant effects of nutraceuticals. Various preclinical and clinical studies were investigated for the Anti-Alzheimer's activity of nutraceuticals. The increasing ability of the pathogenesis of AD has led to the analysis of novel therapeutic targets, including the pathophysiological mechanisms and distinct cascades. So, current improvement will show the most adequate and prominent nutraceuticals and suggested concise mechanisms involving autophagy regulation, anti-inflammatory, antioxidant, mitochondrial homeostasis, and others. The effects of nutraceuticals cannot be ignored; it is important to investigate high-quality clinical trials. Given the potential of nutraceuticals to battle AD as multi-targeted therapies, it's vital to evaluate them as viable lead compounds for drug discovery and development. To the best of the authors 'knowledge, modification of blood-brain barrier permeability, bioavailability, and aspects of randomized clinical trials should be considered in prospective investigations. PRACTICAL APPLICATIONS: Advancements in molecular diagnostic and fundamentals have implemented particular usefulness for drug evaluation. An excess of experimental knowledge occurs regarding the effect of nutraceuticals on AD. There are various preclinical and clinical studies that have been done on nutraceuticals. In addition, various substitute inhibit and enhance some pathophysiological levels associated with AD. Nutraceuticals are easily available and have fewer side effects with cost-effective advantages. However, further investigations and clinical trials are required to encourage its effect on disease.

A Unifying Perspective in Blunting the Limited Oral Bioavailability of Curcumin: A Succinct Look.

BACKGROUND: Curcumin is a polyphenolic compound derived from rhizomes of Curcuma longa, the golden spice. Curcumin has drawn much attention in recent years of biomedical research owing to its wide variety of biologic and pharmacologic actions. It exerts antiproliferative, antifibrogenic, anti-inflammatory, and antioxidative effects, among various imperative pharmacologic actions. In spite of its well-documented efficacies against numerous disease conditions, the limited systemic bioavailability of curcumin is a continuing concern. Perhaps, the poor bioavailability of curcumin may have curtailed its significant development from kitchen to clinic as a potential therapeutic agent. Subsequently, there have been a considerable number of studies over decades researching the scientific basis of curcumin's reduced bioavailability and eventually improvement of its bioavailability employing a variety of therapeutic approaches, for instance, in combination with piperine, the bio-active constituent of black pepper. Piperine has remarkable potential to modulate the functional activity of metabolic enzymes and drug transporters, and thus there has been a great interest in the therapeutic application of this widely used spice as alternative medicine and bioavailability enhancer. Growing body of evidence supports the synergistic potential of curcumin against numerous pathologic conditions when administered with piperine. CONCLUSION: In light of current challenges, the major concern pertaining to poor systemic bioavailability of curcumin, its improvement, especially in combination with piperine, and the necessity of additional research in this setting are together described in this review. Besides, the recent advances in the potential therapeutic rationale and efficacy of curcumin-piperine combination, a promising duo, against various pathologic conditions are delineated.

Possible involvement of PKC-delta in the abrogated cardioprotective potential of ischemic preconditioning in hyperhomocysteinemic rat hearts.

The present study has been designed to investigate the possible role of protein kinase C-delta (PKC-delta) in hyperhomocysteinemia-induced attenuation of cardioprotective potential of ischemic preconditioning (IPC). Rats were administered L-methionine (1.7 g/kg/day, p.o.) for 4 weeks to produce hyperhomocysteinemia. Isolated Langendorff perfused normal and hyperhomocysteinemic rat hearts were subjected to global ischemia for 30 min followed by reperfusion for 120 min. Myocardial infarct size was assessed macroscopically using triphenyltetrazolium chloride (TTC) staining. Coronary effluent was analyzed for lactate dehydrogenase (LDH) and creatine kinase (CK) release to assess the degree of cardiac injury. Moreover, the oxidative stress in heart was assessed by measuring lipid peroxidation and superoxide anion generation. The ischemia-reperfusion (I/R) was noted to produce myocardial injury as assessed in terms of increase in myocardial infarct size, LDH and CK in coronary effluent and oxidative stress in normal and hyperhomocysteinemic rat hearts. In addition, the hyperhomocysteinemic rat hearts showed enhanced I/R-induced myocardial injury with high degree of oxidative stress as compared with normal rat hearts subjected to I/R. Four episodes of IPC (5 min each) afforded cardioprotection against I/R-induced myocardial injury in normal rat hearts as assessed in terms of reduction in myocardial infarct size, LDH, CK and oxidative stress. On the other hand, IPC mediated myocardial protection against I/R-injury was abolished in hyperhomocysteinemic rat hearts. Treatment with rottlerin (10 microM), a selective inhibitor of PKC-delta did not affect the cardioprotective effects of IPC in normal rat hearts; but its treatment significantly restored the cardioprotective potentials of IPC in hyperhomocysteinemic rat hearts. The high degree of oxidative stress produced in hyperhomocysteinemic rat hearts during reperfusion may activate PKC-delta, which may be implicated in the observed paradoxically abrogated cardioprotective potentials of IPC in hyperhomocysteinemic rat hearts.

Possible role of JAK-2 in attenuated cardioprotective effect of ischemic preconditioning in hyperhomocysteinemic rat hearts.

The present study investigated the possible role of Janus kinase-2 (JAK-2) in hyperhomocysteinemia-induced attenuation of the cardioprotective effects of ischemic preconditioning (IPC). Rats were administered L-methionine (1.7 g/kg/day, p.o.) for 4 weeks to produce hyperhomocysteinemia. Isolated Langendorff's perfused normal and hyperhomocysteinemic rat hearts were subjected to global ischemia for 30 min, followed by reperfusion for 120 min. Myocardial infarct size was assessed macroscopically using triphenyltetrazolium chloride staining. Coronary effluent was analyzed for lactate dehydrogenase (LDH) and creatine kinase (CK) release to assess the extent of cardiac injury. The oxidative stress in the heart was assessed by measuring thiobarbituric acid-reactive substances (TBARS), superoxide anion generation and the reduced form of glutathione. Ischemia-reperfusion (I/R) induced oxidative stress by increasing TBARS, superoxide anion generation and decreasing reduced form of glutathione in normal and hyperhomocystenemic rat hearts. Moreover, I/R produced myocardial injury, which was assessed in terms of the increase in myocardial infarct size, LDH and CK release in coronary effluent, and decrease in coronary flow rate in normal and hyperhomocysteinemic rat hearts. The hyperhomocysteinemic rat hearts showed enhanced I/R-induced myocardial injury with a high degree of oxidative stress as compared with normal rat hearts subjected to I/R. Four episodes of IPC (5 min each) afforded cardioprotection against I/R-induced myocardial injury in normal rat hearts as assessed in terms of improvement in coronary flow rate and reduction in myocardial infarct size, levels of LDH, CK, and oxidative stress. On the other hand, IPC-mediated myocardial protection against I/R-injury was abolished in hyperhomocysteinemic rat hearts. Tyrphostin AG490 (5 microM), a selective inhibitor of JAK-2, did not affect the cardioprotective effects of IPC in normal rat hearts, but its administration markedly restored the cardioprotective potential of IPC in hyperhomocysteinemic rat hearts. Administration of diazoxide (30 microM), an ATP-sensitive potassium (K(ATP)) channel opener, also restored the cardioprotective effects of IPC in hyperhomocysteinemic rat hearts. In conclusion, it is suggested that the high degree of oxidative stress produced in hyperhomocysteinemic rat hearts during reperfusion and consequent activation of JAK-2 and closure of K(ATP) channels may be responsible for abolishing the cardioprotective potential of IPC against I/R-induced myocardial injury.

Modulation of cardioprotective effect of ischemic pre- and postconditioning in the hyperhomocysteinemic rat heart.

The present study was designed to investigate the effect of hyperhomocysteinemia (Hhcy) on cardioprotective potentials of ischemic preconditioning (IPC) and postconditioning (IPost). Rats were administered L-methionine (1.7 g/kg/day orally) for 4 weeks to produce Hhcy. Isolated Langendorff-perfused normal and hyperhomocysteinemic rat hearts were subjected to global ischemia for 30 min followed by reperfusion for 120 min. Myocardial infarct size was assessed macroscopically by volume method using triphenyltetrazolium chloride staining. Coronary effluent was analyzed for the release of lactate dehydrogenase (LDH) and creatine kinase (CK) to assess the degree of cardiac injury. Moreover, oxidative stress in the heart was assessed by measuring lipid peroxidation, superoxide anion generation and reduced glutathione. Ischemia-reperfusion (I/R) was noted to produce myocardial injury, as assessed in terms of increase in myocardial infarct size, LDH and CK in coronary effluent and oxidative stress in normal and hyperhomocysteinemic rat hearts. In addition, the hyperhomocysteinemic rat hearts showed enhanced I/R-induced myocardial injury with a high degree of oxidative stress in comparison with normal rat hearts subjected to I/R. Four episodes of IPC (5 min each) and six episodes of IPost (10 s each) afforded cardioprotection against I/R-induced myocardial injury in normal rat hearts, as assessed in terms of reduction in myocardial infarct size, LDH, CK and oxidative stress. However, surprisingly, IPC- and IPost-mediated myocardial protection against I/R injury was abolished in the hyperhomocysteinemic rat heart. It may be concluded that Hhcy may make the heart susceptible to oxidative stress induced by I/R, and that the high degree of oxidative stress produced in the hyperhomocysteinemic rat heart in response to reperfusion may be responsible for abolishing the cardioprotective potential of IPC and IPost against I/R injury.