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Agents and Actions. Supplements 1988
Clinical Trial Review
Topics: Animals; Arthritis, Rheumatoid; Auranofin; Clinical Trials as Topic; Humans; Immune System; In Vitro Techniques; Intestinal Absorption; Neutrophils
PubMed: 3055876
DOI: 10.1007/978-3-0348-9160-8_15 -
Journal of Helminthology Dec 2023Schistosomiasis is a serious tropical disease. Despite extensive research into the etiology of liver fibrosis, effective therapeutic options remain limited. This study...
Schistosomiasis is a serious tropical disease. Despite extensive research into the etiology of liver fibrosis, effective therapeutic options remain limited. This study aims to assess the effectiveness of auranofin in treating hepatic granuloma and fibrogenesis produced by eggs. Auranofin is a gold complex that contains thioglucose tetraacetate and triethylphosphine. Eighty BALB/c male mice were divided into four groups (n=20/group): negative control (GI), positive control (GII), and early (GIII) and late (GIV) treatment groups with oral auranofin according to beginning of treatment 4th week and 6th week post-infection. Mice were infected subcutaneously in a dose of 60±10 cercariae/mouse. Worm counts, egg loads, and oogram patterns were determined. Biochemical, histological, and immunostaining of interleukin-1β (IL-1β), Sirtuin 3 (SIRT3), and smooth muscle actin (SMA) were assessed. GIII showed a significant decrease in the total worm burden and ova/gram in liver tissue (with reduction percent of 63.07% and 78.26%, respectively). Schistosomal oogram patterns, immature and mature ova, also showed a significant decrease. The reduction in granuloma number and size was 40.63% and 48.66%, respectively, in GIII, whereas in GIV, the reduction percent was 76.63% and 67.08%. In addition, the degree of fibrosis was significantly diminished in both treated groups. GIV showed significant reduction in IL-1β and SMA expression and increase in SIRT3 expression. These findings reveal how auranofin suppresses the development of liver fibrosis. Therefore, it is crucial to take another look at auranofin as a prospective medication for the treatment of egg-induced hepatic granuloma and consequent fibrosis.
Topics: Male; Animals; Mice; Schistosoma mansoni; Schistosomiasis mansoni; Auranofin; Prospective Studies; Sirtuin 3; Ovum; Liver; Liver Cirrhosis; Granuloma
PubMed: 38053397
DOI: 10.1017/S0022149X23000792 -
Frontiers in Cellular and Infection... 2023Microbe entry through catheter ports can lead to biofilm accumulation and complications from catheter-related bloodstream infection and ultimately require antimicrobial...
Microbe entry through catheter ports can lead to biofilm accumulation and complications from catheter-related bloodstream infection and ultimately require antimicrobial treatment and catheter replacement. Although strides have been made with microbial prevention by applying standardized antiseptic techniques during catheter implantation, both bacterial and fungal microbes can present health risks to already sick individuals. To reduce microbial adhesion, murine and human catheters were coated with polyurethane and auranofin using a dip coating method and compared to non-coated materials. Upon passage of fluid through the coated material , flow dynamics were not impacted. The unique antimicrobial properties of the coating material auranofin has shown inhibitory activity against bacteria such as and fungi such as . Auranofin coating on catheters at 10mg/mL reduced . accumulation from 2.0 x 10 to 7.8 x 10 CFU for mouse catheters and from 1.6 x 10 to 2.8 x 10 for human catheters, showing an impact to mature biofilms. Assessment of a dual microbe biofilm on auranofin-coated catheters resulted in a 2-log reduction in . and a 3-log reduction in . compared to uncoated catheters. assessment in a murine subcutaneous model demonstrated that catheters coated with 10 mg/mL auranofin reduced independent . and . accumulation by 4-log and 1-log, respectively, compared to non-coated catheters. In conclusion, the auranofin-coated catheters demonstrate proficiency at inhibiting multiple pathogens by decreasing . and . biofilm accumulation.
Topics: Humans; Animals; Mice; Auranofin; Staphylococcus aureus; Bacteria; Biofilms; Candida albicans; Catheters
PubMed: 37313344
DOI: 10.3389/fcimb.2023.1135942 -
Inflammopharmacology Dec 2012More than 30 years ago, auranofin was developed for the treatment of rheumatoid arthritis as a substitution for the injectable gold compounds aurothiomalate and... (Review)
Review
More than 30 years ago, auranofin was developed for the treatment of rheumatoid arthritis as a substitution for the injectable gold compounds aurothiomalate and aurothioglucose. Both the ease of oral administration over intramuscular injections and more potent anti-inflammatory effects in vitro made auranofin seem like an excellent substitute for the traditional injectable gold compounds. Despite efficacy in the treatment of both rheumatoid arthritis and psoriasis, currently, auranofin is seldom used as a treatment for patients with rheumatoid arthritis as more novel anti-rheumatic medications have become available. Despite the decline in its clinical applications, research on auranofin has continued as it shows promise in the treatment of several different diseases. In recent years, advances in technology have allowed researchers to use molecular techniques to identify novel mechanisms of action of auranofin. Additionally, researchers are discovering potential new applications of auranofin. Dual inhibition of inflammatory pathways and thiol redox enzymes by auranofin makes it a new candidate for cancer therapy and treating microbial infections. This review will summarize recently obtained data on the mechanisms of action of auranofin, and potential new applications of auranofin in the treatment of various diseases, including several types of leukaemia, carcinomas, and parasitic, bacterial, and viral infections.
Topics: Animals; Antirheumatic Agents; Auranofin; Bacterial Infections; Humans; Inflammation; Leukemia; Neoplasms; Parasitic Diseases; Virus Diseases
PubMed: 22965242
DOI: 10.1007/s10787-012-0149-1 -
Future Medicinal Chemistry Jun 2019The orphan drug auranofin was recently found to exhibit antimicrobial properties. We explored the efficacy of auranofin by evaluating the minimal inhibitory...
The orphan drug auranofin was recently found to exhibit antimicrobial properties. We explored the efficacy of auranofin by evaluating the minimal inhibitory concentration against a collection of over 500 clinical isolates derived from multiple institutions, inclusive of drug resistant strains. Our evaluation also included continuous exposure of bacteria to auranofin. We found that minimal inhibitory concentrations ranged between 0.125 and 1 mg/l, exerting robust antimicrobial activity against a sizeable clinical collection of the bacteria. Further, we evaluated the propensity of the methicillin-resistant strain MW2 to develop resistance through extended exposure to auranofin. After 25 days, the bacteria remained susceptible. Our data suggest that resistance mechanisms do not currently exist to block auranofin antimicrobial activity.
Topics: Anti-Bacterial Agents; Auranofin; Drug Resistance, Bacterial; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Staphylococcus aureus
PubMed: 31298580
DOI: 10.4155/fmc-2018-0544 -
Cell Biochemistry and Function Dec 2023The intrinsic redox status of cancer cells limits the efficacy of chemotherapeutic drugs. Auranofin, a Food and Drug Administration-approved gold-containing compound,...
The intrinsic redox status of cancer cells limits the efficacy of chemotherapeutic drugs. Auranofin, a Food and Drug Administration-approved gold-containing compound, documented with effective pharmacokinetics and safety profiles in humans, has recently been repurposed for anticancer activity. This study examined the paclitaxel-sensitizing effect of auranofin by targeting redox balance in the MDA-MB-231 and MCF-7 breast cancer cell lines. Auranofin treatment depletes the activities of superoxide dismutase, catalase, and glutathione peroxidase and alters the redox ratio in the breast cancer cell lines. Furthermore, it has been noticed that auranofin augmented paclitaxel-mediated cytotoxicity in a concentration-dependent manner in both MDA-MB-231 and MCF-7 cell lines. Moreover, auranofin increased the levels of intracellular reactive oxygen species (observed using 2, 7-diacetyl dichlorofluorescein diacetate staining) and subsequently altered the mitochondrial membrane potential (rhodamine-123 staining) in a concentration-dependent manner. Further, the expression of apoptotic marker p21 was found to be higher in auranofin plus paclitaxel-treated breast cancer cells compared to paclitaxel-alone treatment. Thus, the present results illustrate the chemosensitizing property of auranofin in MDA-MB-231 and MCF-7 breast cancer cell lines via oxidative metabolism. Therefore, auranofin could be considered a chemosensitizing agent during cancer chemotherapy.
Topics: Humans; Female; Paclitaxel; Auranofin; Breast Neoplasms; Oxidation-Reduction; Cell Line, Tumor; MCF-7 Cells; Apoptosis
PubMed: 37792847
DOI: 10.1002/cbf.3865 -
International Journal of Antimicrobial... Nov 2021Acanthamoebae are opportunistic pathogens that cause serious infections, including Acanthamoeba keratitis, a sight-threatening disease affecting mainly contact lens...
Acanthamoebae are opportunistic pathogens that cause serious infections, including Acanthamoeba keratitis, a sight-threatening disease affecting mainly contact lens wearers, and granulomatous amoebic encephalitis, an infection of the central nervous system that occurs mostly in immunocompromised individuals. Although these infections are rare, they are a challenge for healthcare providers. In the last decade, the search for and implementation of novel treatment approaches against these parasites and the infections they cause have intensified, but current options are still unsatisfactory. The aim of this study was to investigate the in vitro activity of the gold-based compound auranofin against Acanthamoeba spp. The study showed that auranofin has potent antimicrobial activity against Acanthamoeba spp., with an IC ranging from 2.9 to 3.48 µM, and thus may be useful in the prevention and control of Acanthamoeba infections.
Topics: Acanthamoeba; Acanthamoeba Keratitis; Amebiasis; Antiparasitic Agents; Auranofin; Encephalitis; Humans; Parasitic Sensitivity Tests
PubMed: 34419578
DOI: 10.1016/j.ijantimicag.2021.106425 -
Seminars in Arthritis and Rheumatism Aug 1987
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PloS One 2022Neisseria gonorrhoeae has been classified by the U.S. Centers for Disease Control and Prevention as an urgent threat due to the rapid development of antibiotic...
Neisseria gonorrhoeae has been classified by the U.S. Centers for Disease Control and Prevention as an urgent threat due to the rapid development of antibiotic resistance to currently available antibiotics. Therefore, there is an urgent need to find new antibiotics to treat gonococcal infections. In our previous study, the gold-containing drug auranofin demonstrated potent in vitro activity against clinical isolates of N. gonorrhoeae, including multidrug-resistant strains. Therefore, the aim of this study was to investigate the in vivo activity of auranofin against N. gonorrhoeae using a murine model of vaginal infection. A significant reduction in N. gonorrhoeae recovered from the vagina was observed for infected mice treated with auranofin compared to the vehicle over the course of treatment. Relative to the vehicle, after three and five days of treatment with auranofin, a 1.04 (91%) and 1.40 (96%) average log10-reduction of recovered N. gonorrhoeae was observed. In conclusion, auranofin has the potential to be further investigated as a novel, safe anti-gonococcal agent to help meet the urgent need for new antimicrobial agents for N. gonorrhoeae infection.
Topics: Animals; Anti-Bacterial Agents; Auranofin; Disease Models, Animal; Female; Gold; Gonorrhea; Humans; Male; Mice; Microbial Sensitivity Tests; Neisseria gonorrhoeae; Reproductive Tract Infections
PubMed: 35446884
DOI: 10.1371/journal.pone.0266764 -
Antimicrobial Agents and Chemotherapy Sep 2019Nontuberculous mycobacteria (NTM) are highly drug-resistant, opportunistic pathogens that can cause pulmonary disease. The outcomes of the currently recommended...
Nontuberculous mycobacteria (NTM) are highly drug-resistant, opportunistic pathogens that can cause pulmonary disease. The outcomes of the currently recommended treatment regimens are poor, especially for New or repurposed drugs are direly needed. Auranofin, a gold-based antirheumatic agent, was investigated for Here, we test auranofin against NTM and We tested the susceptibility of 63 NTM isolates to auranofin using broth microdilution. Next, we assessed synergy between auranofin and antimycobacterial drugs using the checkerboard method and calculated the fractional inhibition concentration index (FICI). Using time-kill kinetics assays (TK), we assessed pharmacodynamics of auranofin alone and in combination with drug combinations showing the lowest FICIs for CIP 104536. A response surface analysis was used to assess synergistic interactions over time in TKs. Primary isolated macrophages were infected with and treated with auranofin. Finally, using KEGG Orthology, we looked for orthologues to auranofins drug target in had the lowest auranofin MIC (2 μg/ml) among the tested NTM. The lowest average FICIs were observed between auranofin and amikacin (0.45) and linezolid (0.50). Auranofin exhibited concentration-dependent killing of , with >1-log killing at concentrations of >2× MIC. Only amikacin was synergistic with auranofin according to Bliss independence. Auranofin could not lower the intracellular bacterial load in macrophages. Auranofin itself may not be feasible for treatment, but these data point toward a promising, unutilized drug target.
Topics: Anti-Bacterial Agents; Auranofin; Bacterial Proteins; Drug Therapy, Combination; Humans; Kinetics; Macrophages; Microbial Sensitivity Tests; Mycobacterium; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus; Phylogeny; Thioredoxin-Disulfide Reductase
PubMed: 31262763
DOI: 10.1128/AAC.00449-19