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Aging Dec 2023Cisplatin has the potential to cause kidney and reproductive organ injuries, prompting the search for protective agents against cisplatin-induced toxicity. Melatonin, an...
Cisplatin has the potential to cause kidney and reproductive organ injuries, prompting the search for protective agents against cisplatin-induced toxicity. Melatonin, an antioxidant hormone, has shown promise in mitigating oxidative stress in various organs. However, its protective effects on cisplatin-induced kidney and reproductive injuries have not been extensively investigated. The aim of this study was to explore the potential protective effects of melatonin on cisplatin-induced kidney and reproductive injuries when administered in combination with gemcitabine in mice. Male C57BL/6 mice were subjected to a seven-week treatment with gemcitabine plus cisplatin, with or without melatonin intervention. The testis, epididymis, and kidney were assessed through histological analysis and measurement of blood parameters. Treatment with cisplatin led to a significant reduction in testicular weight, histological abnormalities, and alterations in reproductive hormone levels. Melatonin exhibited a slight protective effect on the testis, with higher doses of melatonin yielding better outcomes. However, melatonin did not reverse the effects of cisplatin on the epididymis. Administration of melatonin before and during treatment with cisplatin plus gemcitabine in mice demonstrated a modest protective effect on testicular injuries, while showing limited effects on epididymal injuries. Serum creatinine levels in the group treated with gemcitabine plus cisplatin treatment and high-dose melatonin approached those of the control group, indicating a protective effect on the kidney. These findings underscore the potential of melatonin as a protective agent against cisplatin-induced kidney and reproductive injuries and emphasize the need for further research to optimize its dosage and evaluate its long-term effects.
Topics: Mice; Male; Animals; Cisplatin; Melatonin; Gemcitabine; Mice, Inbred C57BL; Testis; Antioxidants; Oxidative Stress; Kidney; Protective Agents
PubMed: 38097341
DOI: 10.18632/aging.205307 -
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 -
Molecular Medicine (Cambridge, Mass.) Mar 2022Acute lung injury (ALI) and acute respiratory distress syndrome, which is a more severe form of ALI, are life-threatening clinical syndromes observed in critically ill... (Review)
Review
Acute lung injury (ALI) and acute respiratory distress syndrome, which is a more severe form of ALI, are life-threatening clinical syndromes observed in critically ill patients. Treatment methods to alleviate the pathogenesis of ALI have improved to a great extent at present. Although the efficacy of these therapies is limited, their relevance has increased remarkably with the ongoing pandemic caused by the novel coronavirus disease 2019 (COVID-19), which causes severe respiratory distress syndrome. Several studies have demonstrated the preventive and therapeutic effects of molecular hydrogen in the various diseases. The biological effects of molecular hydrogen mainly involve anti-inflammation, antioxidation, and autophagy and cell death modulation. This review focuses on the potential therapeutic effects of molecular hydrogen on ALI and its underlying mechanisms and aims to provide a theoretical basis for the clinical treatment of ALI and COVID-19.
Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents, Non-Steroidal; Humans; Hydrogen; Protective Agents; Sepsis; COVID-19 Drug Treatment
PubMed: 35240982
DOI: 10.1186/s10020-022-00455-y -
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 -
Progress in Lipid Research Jul 2020In this review, steroids with a tertiary butyl group, which are usually called neo steroids, are a small group of natural lipids isolated from higher plants, fungi,... (Review)
Review
In this review, steroids with a tertiary butyl group, which are usually called neo steroids, are a small group of natural lipids isolated from higher plants, fungi, marine sponges, and yeast. In addition, steroids with a tertiary butyl group have been synthesized in some laboratories in Canada, USA, Europe, and Japan and their biological activity was studied. Some natural neo steroids demonstrate antitumor or hepatoprotective activities. In addition, synthetic neo steroids exhibit anticancer and neuroprotective properties. However, to confirm the above data, both practical and clinical experimental studies are necessary. Nevertheless, the results may be useful for pharmacologists, chemists, biochemists, and the pharmaceutical industry.
Topics: Animals; Antineoplastic Agents; Biological Products; Humans; Liver; Molecular Structure; Neoplasms; Protective Agents; Steroids
PubMed: 32603672
DOI: 10.1016/j.plipres.2020.101048 -
Nitric Oxide : Biology and Chemistry Jul 2016Cisplatin is a potent chemotherapeutic agent for the treatment of various solid-organ cancers. However, a plethora of evidence indicates that nephrotoxicity is a major... (Review)
Review
Cisplatin is a potent chemotherapeutic agent for the treatment of various solid-organ cancers. However, a plethora of evidence indicates that nephrotoxicity is a major side effect of cisplatin therapy. While the antineoplastic action of cisplatin is due to formation of cisplatin-DNA cross-links, which damage rapidly dividing cancer cells upon binding to DNA, its nephrotoxic effect results from metabolic conversion of cisplatin into a nephrotoxin and production of reactive oxygen species, causing oxidative stress leading to renal tissue injury and potentially, kidney failure. Despite therapeutic targets in several pre-clinical and clinical studies, there is still incomplete protection against cisplatin-induced nephrotoxicity. Hydrogen sulfide (H2S), the third discovered gasotransmitter next to nitric oxide and carbon monoxide, has recently been identified in several in vitro and in vivo studies to possess specific antioxidant, anti-inflammatory and anti-apoptotic properties that modulate several pathogenic pathways involved in cisplatin-induced nephrotoxicity. The current article reviews the molecular mechanisms underlying cisplatin-induced nephrotoxicity and displays recent findings in the H2S field that could disrupt such mechanisms to ameliorate cisplatin-induced renal injury.
Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Apoptosis; Cisplatin; Humans; Hydrogen Sulfide; Kidney Diseases; Protective Agents
PubMed: 27095538
DOI: 10.1016/j.niox.2016.04.005 -
Molecules (Basel, Switzerland) Dec 2020The inflammatory mediator and oxidant agent storm caused by the SARS-CoV-2 infection has been strongly associated with the failure of vital organs observed in critically... (Review)
Review
The inflammatory mediator and oxidant agent storm caused by the SARS-CoV-2 infection has been strongly associated with the failure of vital organs observed in critically ill patients with coronavirus disease 2019 (COVID-19) and the death of thousands of infected people around the world. Acute kidney injury (AKI) is a common renal disorder characterized by a sudden and sustained decrease in renal function with a critical influence on poor prognosis and lethal clinical outcomes of various etiologies, including some viral infection diseases. It is known that oxidative stress and inflammation play key roles in the pathogenesis and development of AKI. Quercetin is a natural substance that has multiple pharmacological properties, such as anti-inflammatory action, and is used as a dietary supplement. There is evidence of the anti-coronavirus activities of this compound, including against the target SARS-CoV-2 3CLpro. The ability to inhibit coronavirus and its inflammatory processes is strongly desired in a new drug for the treatment of COVID-19. Therefore, in this review, the dual effect of quercetin is discussed from a mechanistic perspective in relation to AKI kidney injury and its nephroprotective potential to SARS-CoV-2 patients.
Topics: Acute Kidney Injury; Animals; COVID-19; Humans; Morbidity; Protective Agents; Quercetin; COVID-19 Drug Treatment
PubMed: 33297540
DOI: 10.3390/molecules25235772