-
Expert Opinion on Drug Metabolism &... Oct 2020Cisplatin is a highly effective chemotherapeutic agent against a variety of solid tumors in adults and in children. Unfortunately, a large percentage of patients suffer... (Review)
Review
INTRODUCTION
Cisplatin is a highly effective chemotherapeutic agent against a variety of solid tumors in adults and in children. Unfortunately, a large percentage of patients suffer permanent sensorineural hearing loss. Up to 60% of children and at least 50% of adults suffer this complication that seriously compromises their quality of life. Hearing loss is due to damage to the sensory cells in the inner ear. The mechanisms of cochlear damage are still being investigated. However, it appears that inner ear damage is triggered by reactive oxygen species (ROS) formation and inflammation 34.
AREAS COVERED
We discuss a number of potential therapeutic targets that can be addressed to provide hearing protection. These strategies include enhancing the endogenous antioxidant pathways, heat shock proteins, G protein coupled receptors and counteracting ROS and reactive nitrogen species, and blocking pathways that produce inflammation, including TRPV1 and STAT1 36.
EXPERT OPINION
Numerous potential protective agents show promise in animal models by systemic or local administration. However, clinical trials have not shown much efficacy to date with the exception of sodium thiosulfate. There is an urgent need to discover safe and effective protective agents that do not interfere with the efficacy of cisplatin against tumors yet preserve hearing 151.
Topics: Adult; Animals; Antineoplastic Agents; Child; Cisplatin; Hearing Loss; Humans; Neoplasms; Ototoxicity; Platinum Compounds; Protective Agents; Quality of Life; Reactive Oxygen Species
PubMed: 32757852
DOI: 10.1080/17425255.2020.1806235 -
Molecules (Basel, Switzerland) Nov 2022CA (cyclosporine A) is a powerful immunosuppressing agent that is commonly utilized for treating various autoimmune illnesses and in transplantation surgery. However,... (Review)
Review
CA (cyclosporine A) is a powerful immunosuppressing agent that is commonly utilized for treating various autoimmune illnesses and in transplantation surgery. However, its usage has been significantly restricted because of its unwanted effects, including nephrotoxicity. The pathophysiology of CA-induced kidney injury involves inflammation, apoptosis, tubular injury, oxidative stress, and vascular injury. Despite the fact that exact mechanism accountable for CA's effects is inadequately understood, ROS (reactive oxygen species) involvement has been widely proposed. At present, there are no efficient methods or drugs for treating CA-caused kidney damage. It is noteworthy that diverse natural products have been investigated both in vivo and in-vitro for their possible preventive potential in CA-produced nephrotoxicity. Various extracts and natural metabolites have been found to possess a remarkable potential for restoring CA-produced renal damage and oxidative stress alterations via their anti-apoptosis, anti-inflammatory, and antioxidative potentials. The present article reviews the reported studies that assess the protective capacity of natural products, as well as dietary regimens, in relation to CA-induced nephrotoxicity. Thus, the present study presents novel ideas for designing and developing more efficient prophylactic or remedial strategies versus CA passive influences.
Topics: Cyclosporine; Kidney; Protective Agents; Oxidative Stress; Anti-Inflammatory Agents; Biological Products
PubMed: 36431872
DOI: 10.3390/molecules27227771 -
Phytomedicine : International Journal... Jul 2024Sulforaphane (SFN) is a dietary isothiocyanate, derived from glucoraphanin, present in cruciferous vegetables belonging to the Brassica genus. It is a biologically... (Review)
Review
BACKGROUND
Sulforaphane (SFN) is a dietary isothiocyanate, derived from glucoraphanin, present in cruciferous vegetables belonging to the Brassica genus. It is a biologically active phytochemical that acts as a nuclear factor erythroid 2-related factor 2 (Nrf2) inducer. Thus, it has been reported to have multiple protective functions including anticancer responses and protection against a toxic agent's action.
PURPOSE
The present work systematically reviewed and synthesised the protective properties of sulforaphane against a toxic agent. This review reveals the mechanism of the action of SFN in each organ or system.
METHODS
The PRISMA guideline was followed in this sequence: researched literature, organised retrieved documents, abstracted relevant information, assessed study quality and bias, synthesised data, and prepared a comprehensive report. Searches were conducted on Science Direct and PubMed using the keywords "Sulforaphane" AND ("protective effects" OR "protection against").
RESULTS
Reports showed that liver and the nervous system are the target organs on which attention was focused, and this might be due to the key role of oxidative stress in liver and neurodegenerative diseases. However, protective activities have also been demonstrated in the lungs, heart, immune system, kidneys, and endocrine system. SFN exerts its protective effects by activating the Nrf2 pathway, which enhances antioxidant defenses and reduces oxidative stress. It also suppresses inflammation by decreasing interleukin production. Moreover, SFN inhibits apoptosis by preventing caspase 3 cleavage and increasing Bcl2 levels. Overall, SFN demonstrates multifaceted mechanisms to counteract the adverse effects of toxic agents.
CONCLUSION
SFN has potential clinical applications as a chemoprotective agent. Nevertheless, more studies are necessary to set the safe doses of SFN in humans.
Topics: Isothiocyanates; Sulfoxides; Humans; Animals; Brassica; Oxidative Stress; NF-E2-Related Factor 2; Protective Agents
PubMed: 38824824
DOI: 10.1016/j.phymed.2024.155731 -
Environmental Pollution (Barking, Essex... May 2022Aggrandized technological and industrial progression in past decades have occasioned immense depreciation in the quality of environment and ecosystem, majorly due to... (Review)
Review
Aggrandized technological and industrial progression in past decades have occasioned immense depreciation in the quality of environment and ecosystem, majorly due to augmentation in the number of obnoxious pollutants incessantly being released in soil, water or air. Arsenic (As) is one such hazardous metalloid contaminating the environment which has the potential to detrimentally affect the life on earth. Even in minute quantity, As is known to cause various critical diseases in humans and toxicity in plants. Recent studies on nanoparticles (NPs) approve of their ability to qualify the criterion of becoming a potent tool for mitigating As-induced phytotoxicity. Nanoparticles are reported to promote plant growth under As-stress by stimulating various alterations at physiological, biochemical, and molecular levels. In this review, we provide an up-to-date compilation of research that has been carried out in comprehending the mechanisms utilized by nanoparticles including controlled As uptake and distribution in plants, maintenance of ROS homeostasis during stress and chelation and vacuolar sequestration of As so as to reduce the severity of toxicity induced by As, and potential areas of research in this field will also be indicated for future perspectives.
Topics: Arsenic; Arsenic Poisoning; Ecosystem; Humans; Nanoparticles; Protective Agents; Soil Pollutants
PubMed: 35077838
DOI: 10.1016/j.envpol.2022.118887 -
Expert Opinion on Drug Safety Aug 2020Cilastatin, a dehydropeptidase I inhibitor, has been used alongside imipenem, a broad spectrum antibiotic, in order to reduce its renal metabolism, consequently... (Review)
Review
INTRODUCTION
Cilastatin, a dehydropeptidase I inhibitor, has been used alongside imipenem, a broad spectrum antibiotic, in order to reduce its renal metabolism, consequently increasing its urinary recovery and effectiveness for many years. However, this measure could be useful in preventing imipenem-induced renal damage and decreasing the number of nephrotoxicity reports with imipenem. In this review, the authors gathered all available studies focusing on cilastatin use as a nephroprotective agent, beside well-known nephrotoxic medications like vancomycin, cisplatin, cyclosporine, or tacrolimus.
AREAS COVERED
PubMed, Scopus, Google Scholar, and Medline databases were searched using key words like 'cilastatin,' 'nephroprotective,' 'nephroprotection,' 'vancomycin,' 'nephrotoxicity,' 'cisplatin,' 'cyclosporine,' 'tacrolimus,' and 'prevention' with varying combinations. All relevant animal and human studies up to the date of publication were included.
EXPERT OPINION
It seems that cilastatin could potentially be effective against drug-induced nephrotoxicity via mechanisms such as reducing reactive oxygen species (ROS) production, apoptosis, P-glycoprotein suppression, and morphological changes of renal cells. Nearly all the in vitro, in vivo and human studies have supported this hypothesis. Though since cilastatin protective effect has not extensively been researched in humans, its efficacy and widespread use with other nephrotoxic agents is yet to be defined in large well-designed human studies.
Topics: Animals; Apoptosis; Cilastatin; Humans; Kidney Diseases; Protease Inhibitors; Protective Agents; Reactive Oxygen Species
PubMed: 32666842
DOI: 10.1080/14740338.2020.1796967 -
Molecules (Basel, Switzerland) Oct 2021The blockade of the progression or onset of pathological events is essential for the homeostasis of an organism. Some common pathological mechanisms involving a wide... (Review)
Review
BACKGROUND
The blockade of the progression or onset of pathological events is essential for the homeostasis of an organism. Some common pathological mechanisms involving a wide range of diseases are the uncontrolled inflammatory reactions that promote fibrosis, oxidative reactions, and other alterations. Natural plant compounds (NPCs) are bioactive elements obtained from natural sources that can regulate physiological processes. Inflammation is recognized as an important factor in the development and evolution of chronic renal damage. Consequently, any compound able to modulate inflammation or inflammation-related processes can be thought of as a renal protective agent and/or a potential treatment tool for controlling renal damage. The objective of this research was to review the beneficial effects of bioactive natural compounds on kidney damage to reveal their efficacy as demonstrated in clinical studies.
METHODS
This systematic review is based on relevant studies focused on the impact of NPCs with therapeutic potential for kidney disease treatment in humans.
RESULTS
Clinical studies have evaluated NPCs as a different way to treat or prevent renal damage and appear to show some benefits in improving OS, inflammation, and antioxidant capacity, therefore making them promising therapeutic tools to reduce or prevent the onset and progression of KD pathogenesis.
CONCLUSIONS
This review shows the promising clinical properties of NPC in KD therapy. However, more robust clinical trials are needed to establish their safety and therapeutic effects in the area of renal damage.
Topics: Antioxidants; Berberine; Beta vulgaris; Betalains; Biological Products; Catechin; Curcumin; Disulfides; Flavonoids; Humans; Isothiocyanates; Kidney; Kidney Diseases; Plant Extracts; Pomegranate; Protective Agents; Resveratrol; Sulfinic Acids; Sulfoxides; Xanthophylls
PubMed: 34684678
DOI: 10.3390/molecules26206096 -
International Journal of Molecular... Jul 2021Mibyou, or pre-symptomatic diseases, refers to state of health in which a disease is slowly developing within the body yet the symptoms are not apparent. Common examples... (Review)
Review
Mibyou, or pre-symptomatic diseases, refers to state of health in which a disease is slowly developing within the body yet the symptoms are not apparent. Common examples of mibyou in modern medicine include inflammatory diseases that are caused by chronic inflammation. It is known that chronic inflammation is triggered by the uncontrolled release of proinflammatory cytokines by neutrophils and macrophages in the innate immune system. In a recent study, it was shown that molecular hydrogen (H) has the ability to treat chronic inflammation by eliminating hydroxyl radicals (·OH), a mitochondrial reactive oxygen species (ROS). In doing so, H suppresses oxidative stress, which is implicated in several mechanisms at the root of chronic inflammation, including the activation of NLRP3 inflammasomes. This review explains these mechanisms by which H can suppress chronic inflammation and studies its applications as a protective agent against different inflammatory diseases in their pre-symptomatic state. While mibyou cannot be detected nor treated by modern medicine, H is able to suppress the pathogenesis of pre-symptomatic diseases, and thus exhibits prospects as a novel protective agent.
Topics: Alzheimer Disease; Animals; Asymptomatic Diseases; Chronic Disease; Diabetes Mellitus, Type 2; Free Radical Scavengers; Hepatitis; Humans; Hydrogen; Hypertension; Inflammation; Models, Biological; Neoplasms; Oxidative Stress; Parkinson Disease; Protective Agents; Renal Insufficiency, Chronic
PubMed: 34281264
DOI: 10.3390/ijms22137211 -
The Journal of International Medical... Aug 2020Cisplatin (CDDP) toxicity is a dose-limiting clinical problem in clinical practice, mainly because of nephrotoxicity or ototoxicity. However, the mechanism of...
OBJECTIVE
Cisplatin (CDDP) toxicity is a dose-limiting clinical problem in clinical practice, mainly because of nephrotoxicity or ototoxicity. However, the mechanism of CDDP-induced cardiotoxicity is poorly understood. Acetyl-l-carnitine (ALCAR) is an antioxidant agent with protective effects against the side effects of various chemotherapeutics. CDDP-induced cardiotoxicity and the protective role of ALCAR were evaluated in this study.
METHODS
Morphological changes were evaluated in hematoxylin and eosin-stained sections, and immunohistochemistry for caspase-3, superoxide dismutase-2 (SOD-2), inducible nitrite oxide synthase (iNOS), cyclooxygenase-2, and Bcl-2 was performed using the hearts of athymic nude mice carrying xenograft neuroblastoma tumors. Mice were randomized (six/group) to the control, CDDP (16 mg/kg), and ALCAR (200 mg/kg)+CDDP (16 mg/kg) groups. Results were analyzed using nonparametric tests.
RESULTS
No difference was observed in the rates of cardiac necrosis, dilated/congested blood vessels, hemorrhage, polymorphonuclear leukocyte infiltration, edema, and pyknotic nuclei among the groups. SOD-2 expression was increased in the CDDP group but not in the ALCAR+CDDP group. iNOS, Bcl-2, and caspase-3 levels were not significantly different among the groups.
CONCLUSIONS
ALCAR might be a candidate protective agent for CDDP-induced cardiotoxicity. SOD-2, as a member of the oxidant system, should be evaluated in further studies as a biomarker of cardiotoxicity.
Topics: Acetylcarnitine; Animals; Antineoplastic Agents; Antioxidants; Cardiotoxicity; Cisplatin; Mice; Mice, Nude
PubMed: 32865065
DOI: 10.1177/0300060520951393 -
European Journal of Pharmacology Oct 2022Sepsis-related acute liver injury (ALI) is a fatal disease associated with many complications. Recent studies indicate that malvidin, an active flavonoid, has multiple...
Sepsis-related acute liver injury (ALI) is a fatal disease associated with many complications. Recent studies indicate that malvidin, an active flavonoid, has multiple bioactivities including anti-oxidant and anti-inflammation. However, the protective roles of malvidin against LPS-induced ALI are unknown. The purpose of this research is to explore whether malvidin has biological activities on LPS-induced ALI in mice and the underlying mechanisms. Male C57 mice were injected intraperitoneally with malvidin for five days and the mice were euthanized 6 h after LPS (10 mg/kg body weight) intraperitoneal injection. Multiple methods of H&E staining, biochemical kits, qRT-PCR assay, western blotting analysis, TUNEL and transmission electron microscope (TEM) were used. Results showed that decreased ALT, AST levels and alleviated histopathological damage of liver tissue were observed in malvidin pretreatment group in mice. Then, malvidin prevented LPS-induced reduction of antioxidant enzyme activities such as superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and catalase (CAT) via up-regulating nuclear factor E2-related factor2 (Nrf2) pathway. In addition, in malvidin pretreatment groups, mRNA levels of pro-inflammatory cytokines (TNF-α,IL-1β, IL-6) and protein levels of NOD-like receptor protein 3 (NLRP3) inflammasome in the liver were significantly down-regulated. We also found that the malvidin could reduce the expression of apoptosis key protein and TUNEL-labeled apoptotic hepatocytes. Furthermore, malvidin inhibited the protein expression of ATG5, p62 and the ratio of LC3-II/LC3-I. In conclusion, our study firstly suggests that malvidin is a potentially protective agent against LPS-induced ALI through up-regulating Nrf2 signaling pathway, suppressing NLRP3 inflammasome and inhibiting apoptosis and autophagy.
Topics: Animals; Anthocyanins; Antioxidants; Apoptosis; Autophagy; Catalase; Chemical and Drug Induced Liver Injury; Cytokines; Glutathione Peroxidase; Inflammasomes; Interleukin-6; Lipopolysaccharides; Male; Mice; NF-E2-Related Factor 2; NLR Family, Pyrin Domain-Containing 3 Protein; NLR Proteins; Protective Agents; RNA, Messenger; Superoxide Dismutase; Tumor Necrosis Factor-alpha
PubMed: 36063870
DOI: 10.1016/j.ejphar.2022.175252 -
Frontiers in Bioscience (Landmark... Mar 2020Osteoporosis is a progressive and chronic bone disorder characterized by low bone mass and microarchitectural deterioration of skeletal tissues. Osteoporosis leads to... (Review)
Review
Osteoporosis is a progressive and chronic bone disorder characterized by low bone mass and microarchitectural deterioration of skeletal tissues. Osteoporosis leads to alteration in bone mineral content resulting in decreased bone strength with elevated fracture risks frequently associated with greater morbidity. The latest research in the area of photomedicine had sparked interest in harnessing the active components from plants in both disease control and management across the globe. We in the present review have taken a comprehensive approach to identify forty known plants and their phytoconstituents, which encompasses (i) the genetic diversity of various plants, (ii) their active components and (iii) their osteoprotective role in osteoporosis. Thus, the present review is an attempt for the first time to collectively document the therapeutic properties of valuable medicinal plants in preventing and treating bone loss in osteoporosis.
Topics: Animals; Bone Density; Bone and Bones; Fractures, Bone; Humans; Osteoporosis; Phytotherapy; Plant Preparations; Plants, Medicinal; Protective Agents
PubMed: 32114432
DOI: 10.2741/4855