Metformin as a Potential Adjuvant Antimicrobial Agent Against Multidrug Resistant Bacteria.

INTRODUCTION: The continuous increase in the incidence of bacterial resistance to existing antibiotics represents a worldwide health burden. A surrogate strategy to combat such crisis is to find compounds that restore the antimicrobial activity of the already existing antibiotics against multidrug resistant bacteria. Metformin is a commonly used antidiabetic medication. It has proven benefits in other diseases including cancer, aging-related and infectious diseases. In this study, the potential effect of metformin as an adjuvant therapy to antibiotics was investigated. METHODS: Two multidrug resistant bacterial strains were used; methicillin-resistant Staphylococcus aureus (MRSA; ATCC 33,591) and multidrug resistant Pseudomonas aeruginosa (ATCC BAA-2114). To assess its efficacy, metformin was combined with several antibiotics: levofloxacin, chloramphenicol, rifampicin, ampicillin, and doxycycline. The antibacterial effect of metformin was tested using the micro broth dilution method. The minimum inhibitory concentration (MIC) was also measured. Cytotoxicity studies were also performed on mammalian cells to assess its safety. RESULTS: Metformin exhibited an antibacterial effect when combined with the antibiotics on the two tested strains. It also showed low toxicity on the mammalian cells. Moreover, synergetic studies showed that metformin enhanced the effect of the combined antibiotics, as these combinations provide either a synergistic or additive effect with significant reduction in the MIC. CONCLUSION: Metformin exerts an adjuvant antibacterial effect; thus, it could be a possible candidate as an adjuvant therapy to reduce antimicrobial resistance.

Every-other day fasting prevents memory impairment induced by high fat-diet: Role of oxidative stress.

Imbalance of diet consumption results in memory and learning deterioration. High-fat diet (HFD) causes neuronal damage and eventually cognitive impairment, which can be related to increasing oxidative stress in the brain. Using the every other day fasting (EODF) paradigm, as a method of dietary restriction is thought to provide protection of learning and memory in several experimental studies. In the current work, the preventive effect of EODF paradigm on memory impairment-induced by HFD was investigated. Adult male Wistar rats were fed with HFD using the EODF paradigm for six weeks. At the end of these six weeks, and while the previous treatment were continued, rats were examined for learning and memory (both the short-term and the long-term memory) using the radial arm water maze (RAWM). Oxidative stress in the brain, namely in the hippocampus was also assessed. Chronic administration of HFD induced impairment in both, short- and long- term memory that was prevented using EODF paradigm. Furthermore, EODF prevented HFD-induced decrease in the activities of the antioxidant enzymes, SOD and catalase along with reduction of glutathione (GSH) level and the ratio of reduced glutathione/oxidized glutathione (GSH/GSSG ratio). The EODF also inhibited rise in oxidized glutathione (GSSG) and thiobarbituric acid reactive substances (TBARS) seen with HFD. In conclusion, EODF ameliorated oxidative stress and memory impairment induced by chronic HFD. This probably, can be explained by the ability of EODF to normalize mechanisms involved in oxidative stress in the hippocampus.

Vitamin D Pretreatment Attenuates Ciprofloxacin-Induced Antibacterial Activity.

BACKGROUND: Ciprofloxacin is an antimicrobial that is commonly used to treat several types of infections. It exerts its antimicrobial activity through interfering with bacterial DNA replication and transcription, leading to increase oxidative stress and eventually bacterial death. Vitamin D, on the other hand, has been found to have DNA protective and antioxidant effects. In the current study, the possible interactive effect of vitamin D on ciprofloxacin-induced cytotoxicity was investigated in various standard bacterial strains. METHODS: The bacterial strains that were used include Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus epidermidis, Acinetobacter baumannii, Proteus mirabilis, and Klebsiella pneumoniae. The antibacterial effect of ciprofloxacin with and without vitamin D treatment of the bacteria was assessed using disc diffusion method and by measuring the minimum inhibitory concentration (MIC) and zones of inhibition of bacterial growth. Moreover, reactive oxygen species (ROS) generation after pretreatment of E. Coli cells with ciprofloxacin and/or vitamin D was measured as a function of as a function of hydrogen peroxide generation. RESULTS: Ciprofloxacin demonstrated a potent antibacterial effect against the tested strains of bacteria. Moreover, pretreatment with vitamin D resulted in protecting the bacteria from the cytotoxicity of ciprofloxacin, this was indicated by the significantly smaller zones of inhibition and higher MIC values compared to ciprofloxacin alone as well as reduced ciprofloxacin-induced ROS generation after treatment with vitamin D. CONCLUSION: Results revealed the possible reduction in the activity of ciprofloxacin when used in combination with vitamin D. This could be explained by the ability of vitamin D to reduce oxidative stress in the bacterial cells.

Edaravone protects from memory impairment induced by chronic L-methionine administration.

Hyperhomocysteinemia is a well-known cause of cognitive impairment and neurodegeneration. Increased oxidative stress in the brain has a major possible role in hyperhomocysteinemia-induced pathogenesis. Edaravone is a potent free radical scavenger that has a neuroprotective effect against memory impairment in several experimental models. The current study investigated the possible protective effect of edaravone in L-methionine-induced vascular dementia in a rat model. L-methionine was given (1.7 mg/kg/day) through oral gavage, while edaravone was given (6 mg/kg/day) intraperitoneally. The administration of methionine and edaravone started concomitantly and continued for a total of 9 weeks. Spatial learning and memory were assessed using the radial arm water maze (RAWM). Changes in the oxidative stress-related biomarkers in the hippocampus were assessed using enzymatic assays. Chronic L-methionine administration resulted in short-term and long-term memory impairment, whereas edaravone prevented such effect. Furthermore, edaravone ameliorated L-methionine induced decrease in the activity of the antioxidant enzymes catalase and glutathione peroxidase as well as the ratio of reduced glutathione to oxidized glutathione (GSH/GSSG ratio). Edaravone also prevented increase in the oxidized glutathione (GSSG) secondary to chronic L-methionine administration. In conclusion, the current study suggests that memory impairment and oxidative stress secondary to chronic L-methionine administration can be prevented by edaravone, probably via enhancing antioxidant mechanisms in the hippocampus.