Oxidative stress plays a dual role in infections. Free radicals protect against invading microorganisms, and they can also cause tissue damage during the resulting inflammation. In the process of infection, there is generation of reactive species by myeloperoxidase, NADPH oxidase, and nitric oxide synthase. On the other hand, reactive species can be generated among others, by cytochrome P450, some metals, and xanthine oxidase. Some pathologies arising during infection can be attributed to oxidative stress and generation of reactive species in infection can even have fatal consequences. This article reviews the basic pathways in which reactive species can accumulate during infectious diseases and discusses the related health consequences.

• MeSH
• Communicable Diseases immunology   physiopathology   MeSH
• Metals metabolism   MeSH
• Humans MeSH
• Metabolic Networks and Pathways MeSH
• NADPH Oxidases metabolism   MeSH
• Oxidative Stress * MeSH
• Peroxidase metabolism   MeSH
• Nitric Oxide Synthase metabolism   MeSH
• Cytochrome P-450 Enzyme System metabolism   MeSH
• Free Radicals immunology   metabolism   toxicity   MeSH
• Xanthine Oxidase metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Metals MeSH
• NADPH Oxidases MeSH
• Peroxidase MeSH
• Nitric Oxide Synthase MeSH
• Cytochrome P-450 Enzyme System MeSH
• Free Radicals MeSH
• Xanthine Oxidase MeSH

BACKGROUND: Galantamine is a drug used for the treatment of Alzheimer's disease and some other cognitive disorders. It is an inhibitor of acetylcholinesterase; however, interaction with nicotinic acetylcholine receptors has also been reported. Owing to the significant role of cholinergic anti-inflammatory pathways in neuro-immunomodulation, we decided to examine the effect of galantamine on tularemia-infected BALB/c mice. METHODS: Animals were infected with Francisella tularensis LVS and treated with galantamine (0.1 mg/kg of body weight). Total mortality over the course of tularemia infection was assessed and interleukin 6 (IL-6) and interferon gamma (IFN-gamma) in plasma samples were measured by enzyme-linked immunosorbent assays. Apart from the cytokine assays, biochemical markers such as inorganic phosphate, uric acid, lactate dehydrogenase, gamma glutamyltransferase, creatinine phosphokinase and amylase were assayed. RESULTS: The modulation of immunity by galantamine depended on two opposing processes: up-regulation of IFN-gamma and down-regulation of IL-6. Tularemia infection resulted in significant nephropathy, as hyperphosphataemia and hyperuricaemia occurred in infected animals. In addition, galantamine resulted in the mitigation of nephropathy, and markers of kidney dysfunction were modulated. Alterations in mortality were also found in this study. CONCLUSIONS: Galantamine can significantly influence the immune response via the cholinergic anti-inflammatory pathway. Despite the decrease in IL-6 levels, galantamine treatment enhanced protection against the intracellular pathogen F. tularensis, resulting in the remission of some pathology and reduced mortality.

• Keywords
• Acetylcholinesterase, Immunity, Tularemia, Inflammation,
• MeSH
• Survival Analysis MeSH
• Francisella tularensis drug effects   MeSH
• Galantamine pharmacology   therapeutic use   MeSH
• Interferon-gamma blood   MeSH
• Interleukin-6 blood   MeSH
• Mice, Inbred BALB C MeSH
• Mice MeSH
• Tularemia blood   drug therapy   microbiology   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Galantamine MeSH
• Interferon-gamma MeSH
• Interleukin-6 MeSH

Francisella tularensis is the causative agent of tularemia. It is an intracellular pathogen with the ability to survive within phagosomes and induce pyroptotic cell death. In this study, we attempted to prove whether oxidative imbalance plays a significant role in tularemia pathogenesis. In our experimental model, we subcutaneously infected female BALB/c mice (dose 10(5) CFU of F. tularensis LVS). Liver, spleen, and blood were collected from mice at regular intervals from days 1-15 after infection. The bacterial burden was assessed by a cultivation test. The burden was unchanging from the 2(nd) to 6(th) day after infection. The bacterial burden corresponded to the plasmatic level of IFN-γ, IL-6, and liver malondialdehyde. After the phase of acute bacteraemia and the innate immunity reaction, the levels of reduced glutathione and total low molecular weight antioxidants decreased significantly and the activity of caspase-3 increased in the liver. The level of reduced glutathione decreased to 25% of the original level, and the total level of low molecular weight antioxidants was less than 50% of the initial amount. The demonstrated effects of tularemia-induced pathology had a more extensive impact on the liver than on the spleen.

• MeSH
• Antioxidants analysis   MeSH
• Bacterial Load MeSH
• Francisella tularensis pathogenicity   MeSH
• Interferon-gamma blood   MeSH
• Interleukin-6 blood   MeSH
• Liver microbiology   MeSH
• Blood microbiology   MeSH
• Malondialdehyde analysis   MeSH
• Disease Models, Animal MeSH
• Mice, Inbred BALB C MeSH
• Mice MeSH
• Oxidative Stress * MeSH
• Spleen microbiology   MeSH
• Tularemia microbiology   pathology   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Antioxidants MeSH
• Interferon-gamma MeSH
• Interleukin-6 MeSH
• Malondialdehyde MeSH