-
Molecules (Basel, Switzerland) Apr 2020Silymarin extracted from milk thistle consisting of flavonolignan silybin has shown chemopreventive and chemosensitizing activity against various cancers. The present... (Review)
Review
Silymarin extracted from milk thistle consisting of flavonolignan silybin has shown chemopreventive and chemosensitizing activity against various cancers. The present review summarizes the current knowledge on the potential targets of silymarin against various cancers. Silymarin may play on the system of xenobiotics, metabolizing enzymes (phase I and phase II) to protect normal cells against various toxic molecules or to protect against deleterious effects of chemotherapeutic agents on normal cells. Furthermore, silymarin and its main bioactive compounds inhibit organic anion transporters (OAT) and ATP-binding cassettes (ABC) transporters, thus contributing to counteracting potential chemoresistance. Silymarin and its derivatives play a double role, namely, limiting the progression of cancer cells through different phases of the cycle-thus forcing them to evolve towards a process of cell death-and accumulating cancer cells in a phase of the cell cycle-thus making it possible to target a greater number of tumor cells with a specific anticancer agent. Silymarin exerts a chemopreventive effect by inducing intrinsic and extrinsic pathways and reactivating cell death pathways by modulation of the ratio of proapoptotic/antiapoptotic proteins and synergizing with agonists of death domains receptors. In summary, we highlight how silymarin may act as a chemopreventive agent and a chemosensitizer through multiple pathways.
Topics: ATP-Binding Cassette Transporters; Apoptosis; Cell Cycle; Cell Cycle Checkpoints; Chemoprevention; Drug Resistance, Neoplasm; Humans; Protective Agents; Signal Transduction; Silymarin
PubMed: 32344919
DOI: 10.3390/molecules25092009 -
Aging Aug 2019
Topics: Aging; Animals; Muscle, Skeletal; Protective Agents; Sarcopenia; Sirolimus
PubMed: 31454792
DOI: 10.18632/aging.102176 -
Food and Chemical Toxicology : An... Feb 2020Cisplatin has dramatically improved the survival rate of cancer patients, but it has also increased the prevalence of hearing and neurological deficits in this... (Review)
Review
Cisplatin has dramatically improved the survival rate of cancer patients, but it has also increased the prevalence of hearing and neurological deficits in this population. Cisplatin induces ototoxicity, peripheral (most prevalent) and central (rare) neurotoxicity. This review addresses the ototoxicity and the neurotoxicity associated with cisplatin-based chemotherapy, providing an integrated view of the potential protective agents that have been evaluated in vitro, in vivo and in clinical trials, their targets and mechanisms of protection and their effects on the antitumor activity of cisplatin. So far, the findings are insufficient to support the use of any oto- or neuroprotective agent before, during or after cisplatin chemotherapy. Despite their promising effects in vitro and in animal studies, many agents have not been evaluated in clinical trials. Additionally, the clinical trials have limitations concerning the sample size, controls, measurement, heterogeneous groups, several arms of treatment, short follow-up or no blinding. Besides that, for most agents, the effects on the antitumor activity of cisplatin have not been evaluated in tumor-bearing animals, which discourages clinical trials. Further well-designed randomized controlled clinical trials are necessary to definitely demonstrate the effectiveness of the oto- or neuroprotective agents proposed by animal and in vitro studies.
Topics: Animals; Antineoplastic Agents; Cisplatin; Humans; Neoplasms; Neurotoxicity Syndromes; Ototoxicity; Protective Agents
PubMed: 31891754
DOI: 10.1016/j.fct.2019.111079 -
Arhiv Za Higijenu Rada I Toksikologiju Dec 2016Ectoine is a compatible water molecule-binding solute (osmoprotectant) produced by several bacterial species in response to osmotic stress and unfavourable environmental... (Review)
Review
Ectoine is a compatible water molecule-binding solute (osmoprotectant) produced by several bacterial species in response to osmotic stress and unfavourable environmental conditions. This amino acid derivative can accumulate inside cells at high concentrations without interfering with natural processes and can protect the cell against radiation or osmotic stress. This brief review presents the current state of knowledge about the effects of ectoine on animals and focuses on its practical use for enzyme stabilisation, human skin protection, anti-inflammatory treatment, inhibitory effects in neurodegenerative diseases, and other therapeutic potential in human or veterinary medicine.
Topics: Amino Acids, Diamino; Animals; Cell Membrane; Humans; Osmotic Pressure; Protective Agents; Radiation Injuries
PubMed: 28033102
DOI: 10.1515/aiht-2016-67-2837 -
American Journal of Physiology. Renal... Dec 2016Lithium has been a valuable treatment for bipolar affective disorders for decades. Clinical use of lithium, however, has been problematic due to its narrow therapeutic... (Review)
Review
Lithium has been a valuable treatment for bipolar affective disorders for decades. Clinical use of lithium, however, has been problematic due to its narrow therapeutic index and concerns for its toxicity in various organ systems. Renal side effects associated with lithium include polyuria, nephrogenic diabetes insipidus, proteinuria, distal renal tubular acidosis, and reduction in glomerular filtration rate. Histologically, chronic lithium nephrotoxicity is characterized by interstitial nephritis with microcyst formation and occasional focal segmental glomerulosclerosis. Nevertheless, this type of toxicity is uncommon, with the strongest risk factors being high serum levels of lithium and longer time on lithium therapy. In contrast, in experimental models of acute kidney injury and glomerular disease, lithium has antiproteinuric, kidney protective, and reparative effects. This paradox may be partially explained by lower lithium doses and short duration of therapy. While long-term exposure to higher psychiatric doses of lithium may be nephrotoxic, short-term low dose of lithium may be beneficial and ameliorate kidney and podocyte injury. Mechanistically, lithium targets glycogen synthase kinase-3β, a ubiquitously expressed serine/threonine protein kinase implicated in the processes of tissue injury, repair, and regeneration in multiple organ systems, including the kidney. Future studies are warranted to discover the exact "kidney-protective dose" of lithium and test the effects of low-dose lithium on acute and chronic kidney disease in humans.
Topics: Animals; Glomerular Filtration Rate; Humans; Kidney; Kidney Diseases; Lithium; Protective Agents; Psychotic Disorders
PubMed: 27122541
DOI: 10.1152/ajprenal.00145.2016 -
Experimental Animals Nov 2021The aim of this review is to analyze the cardiorespiratory and tissue-protective effects of caffeine in animal models. Peer-reviewed literature published between 1975... (Review)
Review
The aim of this review is to analyze the cardiorespiratory and tissue-protective effects of caffeine in animal models. Peer-reviewed literature published between 1975 and 2021 was retrieved from CAB Abstracts, PubMed, ISI Web of Knowledge, and Scopus. Extracted data were analyzed to address the mechanism of action of caffeine on cardiorespiratory parameters (heart rate and rhythm), vasopressor effects, and some indices of respiratory function; we close this review by discussing the current debate on the research carried out on the effects of caffeine on tissue protection. Adenosine acts through specific receptors and is a negative inotropic and chronotropic agent. Blockage of its cardiac receptors can cause tachycardia (with arrhythmogenic potential) due to the intense activity of β1 receptors. In terms of tissue protection, caffeine inhibits hyperoxia-induced pulmonary inflammation by decreasing proinflammatory cytokine expression in animal models. The protection that caffeine provides to tissues is not limited to the CNS, as studies have demonstrated that it generates attenuation of inflammatory effects in pulmonary tissue. It inhibits the effects of some pro-inflammatory cytokines and prevents functional and structural changes.
Topics: Animals; Caffeine; Disease Models, Animal; Heart Rate; Mice; Protective Agents; Rats; Respiratory Function Tests
PubMed: 34039788
DOI: 10.1538/expanim.20-0185 -
Biomedicine & Pharmacotherapy =... Jul 2021Erythropoietin (Epo) is a pleiotropic cytokine, essential for erythropoiesis. Epo and its receptor (Epo-R) are produced by several tissues and it is now admitted that... (Review)
Review
Erythropoietin (Epo) is a pleiotropic cytokine, essential for erythropoiesis. Epo and its receptor (Epo-R) are produced by several tissues and it is now admitted that Epo displays other physiological functions than red blood cell synthesis. Indeed, Epo provides cytoprotective effects, which consist in prevention or fight against pathological processes. This perspective article reviews the various protective effects of Epo in several organs and tries to give a proof of concept about its effects in the lung. The tissue-protective effects of Epo could be a promising approach to limit the symptoms of acute and chronic lung diseases.
Topics: Animals; Erythropoietin; Humans; Lung Diseases; Protective Agents; Receptors, Erythropoietin; Recombinant Proteins
PubMed: 33831836
DOI: 10.1016/j.biopha.2021.111547 -
Cardiovascular & Hematological Agents... 2019Chrysin is one of the flavonoids fruits, vegetables, and plant especially found in honey, it has been indicated that its cardiovascular protective effect is due to its... (Review)
Review
Chrysin is one of the flavonoids fruits, vegetables, and plant especially found in honey, it has been indicated that its cardiovascular protective effect is due to its antioxidative effects and anti inflammatory activities. Chrysin exerts an antioxidant effect by enhancing the antioxidant system, suppressing pro-oxidant enzymes, scavenging free radicals and chelating redox active transition metal ions. Chrysin decreases lipid synthesis and also increases its metabolism, thereby ameliorating blood lipid profile. Chrysin modulates vascular function by increasing the bioavailability of endothelial nitric oxide. Chrysin inhibits the development of atherosclerosis by decreasing vascular inflammation. The anti-inflammatory effects of chrysin may relate to its inhibitory effect on the nuclear transcriptional factor-kB signaling pathway. It also prevents vascular smooth muscle cells proliferation and thrombogenesis. Altogether, chrysin may be effective as a natural agent for the prevention and treatment of cardiovascular diseases; however, several clinical trial studies should be done to confirm its protective effects on humans.
Topics: Animals; Antioxidants; Cardiotonic Agents; Cardiovascular Diseases; Flavonoids; Humans; Lipid Metabolism; Nitric Oxide; Oxidative Stress
PubMed: 30648526
DOI: 10.2174/1871525717666190114145137 -
Oxidative Medicine and Cellular... 2015Mitochondria are cytoplasmic organelles that regulate both metabolic and apoptotic signaling pathways; their most highlighted functions include cellular energy... (Review)
Review
Mitochondria are cytoplasmic organelles that regulate both metabolic and apoptotic signaling pathways; their most highlighted functions include cellular energy generation in the form of adenosine triphosphate (ATP), regulation of cellular calcium homeostasis, balance between ROS production and detoxification, mediation of apoptosis cell death, and synthesis and metabolism of various key molecules. Consistent evidence suggests that mitochondrial failure is associated with early events in the pathogenesis of ageing-related neurodegenerative disorders including Parkinson's disease and Alzheimer's disease. Mitochondria-targeted protective compounds that prevent or minimize mitochondrial dysfunction constitute potential therapeutic strategies in the prevention and treatment of these central nervous system diseases. This paper provides an overview of the involvement of mitochondrial dysfunction in Parkinson's and Alzheimer's diseases, with particular attention to in vitro and in vivo studies on promising endogenous and exogenous mitochondria-targeted protective compounds.
Topics: Alzheimer Disease; Animals; Disease Models, Animal; Humans; Mitochondria; Parkinson Disease; Protective Agents
PubMed: 26064418
DOI: 10.1155/2015/408927 -
Medicinal Research Reviews Sep 2018To follow-up on our prior Part I review, this Part II review summarizes and provides updated literature on novel quinoline and quinazoline alkaloids isolated during the... (Review)
Review
To follow-up on our prior Part I review, this Part II review summarizes and provides updated literature on novel quinoline and quinazoline alkaloids isolated during the period of 2009-2016, together with the biological activity and the mechanisms of action of these classes of natural products. Over 200 molecules with a broad range of biological activities, including antitumor, antiparasitic and insecticidal, antibacterial and antifungal, cardioprotective, antiviral, anti-inflammatory, hepatoprotective, antioxidant, anti-asthma, antitussive, and other activities, are discussed. This survey should provide new clues or possibilities for the discovery of new and better drugs from the original naturally occurring quinoline and quinazoline alkaloids.
Topics: Alkaloids; Anti-Inflammatory Agents; Antioxidants; Humans; Protective Agents; Quinazolines; Quinolines
PubMed: 29485730
DOI: 10.1002/med.21492