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Renal Failure Dec 2023Patients with diabetic kidney disease (DKD) are at increased risk to develop post-contrast acute kidney injury (AKI). Diabetic patients under dipeptidyl peptidase 4... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Patients with diabetic kidney disease (DKD) are at increased risk to develop post-contrast acute kidney injury (AKI). Diabetic patients under dipeptidyl peptidase 4 inhibitors (DPP4Is) experience a lower propensity to develop AKI. We speculated that linagliptin as a single agent or in combination with allopurinol may reduce the incidence of post-contrast AKI in stage 3-5 chronic kidney disease (CKD) patients with underlying DKD.
METHODS
Out of 951 DKD patients eligible for this study, 800 accepted to sign informed consent. They were randomly allocated to 4 equal groups that received their prophylaxis for 2 days before and after radiocontrast. The first control group received N-acetyl cysteine and saline, the 2 received allopurinol, the 3 group received linagliptin, and the 4 received both allopurinol and linagliptin. Post-procedure follow-up for kidney functions was conducted for 2 weeks in all patients.
RESULTS
20, 19, 14, and 8 patients developed post-contrast AKI in groups 1 through 4, respectively. Neither linagliptin nor allopurinol was superior to N-acetyl cysteine and saline alone. However, the combination of the two agents provided statistically significant renal protection: post-contrast AKI in group 4 was significantly lower than in groups 1 and 2 ( < 0.02 and <0.03, respectively). None of the post-contrast AKI cases required dialysis.
CONCLUSION
Linagliptin and allopurinol in combination may offer protection against post-contrast AKI in DKD exposed to radiocontrast. Further studies are needed to support this view.
TRIAL REGISTRATION CLINICALTRIALS.GOV
NCT03470454.
Topics: Humans; Acute Kidney Injury; Allopurinol; Diabetic Nephropathies; Kidney Failure, Chronic; Linagliptin; Prospective Studies; Renal Insufficiency, Chronic; Contrast Media; Chemoprevention; Drug Therapy, Combination; Acetylcysteine; Protective Agents; Saline Solution
PubMed: 36974638
DOI: 10.1080/0886022X.2023.2194434 -
Molecular Pharmaceutics Nov 2023Amifostine (AMF, also known as WR-2721) is the only approved broad-spectrum small-molecule radiation protection agent that can combat hematopoietic damage caused by... (Review)
Review
Amifostine (AMF, also known as WR-2721) is the only approved broad-spectrum small-molecule radiation protection agent that can combat hematopoietic damage caused by ionizing radiation and is used as an antitumor adjuvant and cell protector in cancer chemotherapy and radiotherapy. Amifostine is usually injected intravenously before chemotherapy or radiotherapy and has been used in the treatment of head and neck cancer. However, the inconvenient intravenous administration and its toxic side effects such as hypotension have severely limited its further application in clinic. In order to reduce the toxic and side effects, scientists are trying to develop a variety of drug administration methods and are devoted to developing a wide application of amifostine in radiation protection. This paper reviews the research progress of amifostine for radiation protection in recent years, discusses its mechanism of action, clinical application, and other aspects, with focus on summarizing the most widely studied amifostine injection administration and drug delivery systems, and explored the correlation between various administrations and drug efficacies.
Topics: Humans; Amifostine; Radiation Protection; Radiation-Protective Agents; Administration, Intravenous; Adjuvants, Immunologic; Drug-Related Side Effects and Adverse Reactions
PubMed: 37747899
DOI: 10.1021/acs.molpharmaceut.3c00600 -
Molecules (Basel, Switzerland) May 2022Foods rich in antioxidants such as lycopene have a major role in maintaining cardiac health. Lycopene, 80% of which can be obtained by consuming a common vegetable such... (Review)
Review
Foods rich in antioxidants such as lycopene have a major role in maintaining cardiac health. Lycopene, 80% of which can be obtained by consuming a common vegetable such as tomato, can prevent the disturbances that contribute to cardiovascular disease (CVD). The present work begins with a brief introduction to CVD and lycopene and its various properties such as bioavailability, pharmacokinetics, etc. In this review, the potential cardio-protective effects of lycopene that reduce the progression of CVD and thrombotic complications are detailed. Further, the protective effects of lycopene including in vitro, in vivo and clinical trials conducted on lycopene for CVD protective effects are explained. Finally, the controversial aspect of lycopene as a protective agent against CVD and toxicity are also mentioned.
Topics: Antioxidants; Cardiovascular Diseases; Carotenoids; Heart Disease Risk Factors; Humans; Lycopene; Risk Factors
PubMed: 35630709
DOI: 10.3390/molecules27103235 -
Food Research International (Ottawa,... May 2022Present study was conducted to comprehensively investigate the protective effects of galactooligosaccharides (GOS, 100%) against LPS-induced intestinal barrier damages,...
Present study was conducted to comprehensively investigate the protective effects of galactooligosaccharides (GOS, 100%) against LPS-induced intestinal barrier damages, and the regulatory effect for intestinal microbes. Results showed that GOS intervention restored villi (jejunum and ileum) integrity, which were atrophic and broken in LPS-challenged mice. Electron microscopy, western blotting and immunofluorescence analysis exhibited that mice administrated with GOS showed higher expression of tight junction, which was confirmed in IPEC-J2 cells model. Meanwhile, the GOS increased the secretion of mucin and SIgA, as well as it alleviated inflammatory response caused by LPS in NF-κB dependent way. Administration of GOS could also increase the relative abundances of several specific friendly bacteria, and enhance the adaptability of intestinal microbiota. Collectively, these results indicated the potential of GOS for protecting intestine from injuries caused by stress as LPS challenge.
Topics: Animals; Cell Line; Gastrointestinal Microbiome; Intestines; Lipopolysaccharides; Mice; Protective Agents
PubMed: 35400418
DOI: 10.1016/j.foodres.2022.111003 -
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 -
Phytomedicine : International Journal... Nov 2022Radiation hazards are accountable for extensive damage in the biological system and acts as a public health burden. Owing to the rapid increasing in radiation... (Review)
Review
BACKGROUND
Radiation hazards are accountable for extensive damage in the biological system and acts as a public health burden. Owing to the rapid increasing in radiation technology, both Ionizing radiation (IR) from natural and man made source poses detrimental outcome to public health. IR releases free radicals which induces oxidative stress and deleterious biological damage by modulating radiation induced signalling intermediates. The efficacy of existing therapeutic approach and treatment strategy are limited owing to their toxicity and associated side effects. Indian system of traditional medicine is enriched with prospective phytochemicals with potential radioprotection ability.
PURPOSE
The present review elucidated and summarized the potential role of plant derived novel chemical compound with prospective radioprotective potential.
METHOD
So far as the traditional system of Indian medicine is concerned, plant kingdom is enriched with potential bioactive molecules with diverse pharmacological activities. We reviewed several compounds mostly secondary metabolites from plant origin using various search engines.
RESULTS
Both compounds from land plants and marine source exhibited antioxidant antiinflammatory, free radical scavenging ability. These compounds have tremendous potential in fine-tuning of several signalling intermediates, which are actively participated in the progression and development of a pathological condition associated with radiation stress.
CONCLUSION
Development and explore of an operational radioprotective agent from originated from plant source that can be used as a novel molecular tool to eliminate the widespread damage caused by space exploration, ionizing radiation, nuclear war and radiotherapy has been significantly appreciated. Through extensive literature search we highlighted several compounds from both land plant and marine origin can be implemented for a better therapeutic potential against radiation induced injury. Furthermore, extensive clinical trials must be carried out in near future for better therapeutic modality and clinical efficacy.
Topics: Antioxidants; Free Radicals; Humans; Phytochemicals; Prospective Studies; Radiation Injuries; Radiation-Protective Agents
PubMed: 36029645
DOI: 10.1016/j.phymed.2022.154188 -
Advances in Gerontology = Uspekhi... 2020Radiation-protective and anti-aging properties are often combined. Combination of this properties is linked to the common mechanisms of action such as direct and...
Radiation-protective and anti-aging properties are often combined. Combination of this properties is linked to the common mechanisms of action such as direct and indirect antioxidant activities, inhibition of free radicals formation, increase resistance to stress impacts at the cellular level, acceleration of DNA reparation, prevention of chronic diseases linked to abnormalities in regeneration processes, activation of immune inflammatory processes and carcinogenesis. Regulation of cell cycle and apoptosis can often be considered as an implementing driver of radiation-protective and anti-aging activities. On the one hand, against the background of stopping the cell cycle and blockade of apoptosis increases the time required to repair the defects of a DNA. Antiapoptotic effects enhances survival chances at the early stage after irradiation in a particular range of doses. On the other hand, activation of apoptosis of altered cells can be seen as one of the mechanisms to delay aging processes and prevention of isolated effects of exposure to ionizing radiation. Formation of radiation-induced and age-related alterations are characterized by multiple factors and a variety of manifestations. Nevertheless, similarity of individual links of the pathogenesis of disease related to radiation exposure and aging of the body is striking. It could be stated that radiation-protective property defines an increase in life expectancy by short-term exposure in sub-lethal and lethal doses. However anti-aging activities prevent the development of remote effects of ionizing radiation by prolonged low doses or fractionated exposure to radiation.
Topics: Apoptosis; DNA Damage; Dose-Response Relationship, Radiation; Radiation, Ionizing; Radiation-Protective Agents
PubMed: 33342093
DOI: No ID Found -
Bioorganic Chemistry Jan 2020Polydatin(PD), a natural active ingredient isolated from traditional Chinese herb Polygonum cuspidatum, is also found in daily foods such as grapes and red wine. It... (Review)
Review
Polydatin(PD), a natural active ingredient isolated from traditional Chinese herb Polygonum cuspidatum, is also found in daily foods such as grapes and red wine. It might play a potential therapeutic role in human health through its anti-inflammatory, anti-oxidant, anti-ischemia injury, anti-apoptosis, conditioning blood lipids and other effects, which makes it increasingly become a hotspot of research. Various studies have shown that PD has a protective effect in the ischemia-reperfusion injury of heart, lungs, kidneys, gastrointestinal tract, cerebra and other organs. However, the specific mechanism of action is less and not completely clear. In this study, we aim to review the protective mechanism of PD in the ischemia-reperfusion injury of various organs, and provide inspiration for future studies.
Topics: Animals; Drugs, Chinese Herbal; Fallopia japonica; Glucosides; Humans; Medicine, Chinese Traditional; Molecular Conformation; Protective Agents; Reperfusion Injury; Stilbenes
PubMed: 31836186
DOI: 10.1016/j.bioorg.2019.103485 -
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