Immunomodulatory Effect of Glutoxim on Some Activities of Isolated Human Neutrophils and in Whole Blood

Fimiani, Vincenzo; Cavallaro, Antonia; Ainis, Tommaso; Baranovskaia, Galina; Ketlinskaya, Olga; Kozhemyakin, L. A.

doi:10.1081/iph-120016039

Cited by 6 publications

(4 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Glutoxim has a immunomodulating effect on lymphocytes showing chemoattractant activity on cells and inhibiting fMLP-induced chemotaxis. Fimiani et al, 2002 50 mg/kg Glutoxim increased the receptor-mediated expression of GR, GPx and GTS, increased the expression of HSP70 in the model of acute cerebral ischemia. systems for the regulation of many cellular processes.…”

Section: Belenichev Et Al 2020mentioning

confidence: 90%

“…The positive effects of the drug on LP markers are described, glutoxim reduces the level of diene conjugates and malonaldehyde against the background of an increase in the antioxidant enzymes SOD and catalase ( Belenichev et al, 2020 ; Table 2 ). Today, the drug is successfully used in phthisiology, oncology, gastroenterology, gynecology, narcology, and toxicology, surgery ( Fimiani et al, 2002 ; Wasinger et al, 2018 ).…”

Section: Possible Pathways For Activation Of Hsp70-dependent Mechanis...mentioning

confidence: 99%

See 1 more Smart Citation

Involvement of heat shock proteins HSP70 in the mechanisms of endogenous neuroprotection: the prospect of using HSP70 modulators

Беленичев

Aliyeva

Popazova

et al. 2023

Front. Cell. Neurosci.

View full text Add to dashboard Cite

This analytical review summarizes literature data and our own research on HSP70-dependent mechanisms of neuroprotection and discusses potential pharmacological agents that can influence HSP70 expression to improve neurological outcomes and effective therapy. The authors formed a systemic concepts of the role of HSP70-dependent mechanisms of endogenous neuroprotection aimed at stopping the formation of mitochondrial dysfunction, activation of apoptosis, desensitization of estrogen receptors, reduction of oxidative and nitrosative stress, prevention of morpho-functional changes in brain cells during cerebral ischemia, and experimentally substantiated new target links for neuroprotection. Heat shock proteins (HSPs) are an evolutionarily integral part of the functioning of all cells acting as intracellular chaperones that support cell proteostasis under normal and various stress conditions (hyperthermia, hypoxia, oxidative stress, radiation, etc.). The greatest curiosity in conditions of ischemic brain damage is the HSP70 protein, as an important component of the endogenous neuroprotection system, which, first of all, performs the function of intracellular chaperones and ensures the processes of folding, holding and transport of synthesized proteins, as well as their degradation, both under normoxic conditions and stress-induced denaturation. A direct neuroprotective effect of HSP70 has been established, which is realized through the regulation the processes of apoptosis and cell necrosis due to a long-term effect on the synthesis of antioxidant enzymes, chaperone activity, and stabilization of active enzymes. An increase in the level of HSP70 leads to the normalization of the glutathione link of the thiol-disulfide system and an increase in the resistance of cells to ischemia. HSP 70 is able to activate and regulate compensatory ATP synthesis pathways during ischemia. It was found that in response to the cerebral ischemia formation, HIF-1a is expressed, which initiates the launch of compensatory mechanisms for energy production. Subsequently, the regulation of these processes switches to HSP70, which “prolongs” the action of HIF-1a, and also independently maintains the expression of mitochondrial NAD-dependent malate dehydrogenase activity, thereby maintaining the activity of the malate-aspartate shuttle mechanism for a long time. During ischemia of organs and tissues, HSP70 performs a protective function, which is realized through increased synthesis of antioxidant enzymes, stabilization of oxidatively damaged macromolecules, and direct anti-apoptotic and mitoprotective action. Such a role of these proteins in cellular reactions during ischemia raises the question of the development of new neuroprotective agents which are able to provide modulation/protection of the genes encoding the synthesis of HSP 70 and HIF-1a proteins. Numerous studies of recent years have noted the important role of HSP70 in the implementation of the mechanisms of metabolic adaptation, neuroplasticity and neuroprotection of brain cells, so the positive modulation of the HSP70 system is a perspective concept of neuroprotection, which can improve the efficiency of the treatment of ischemic-hypoxic brain damage and be the basis for substantiating of the feasibility of using of HSP70 modulators as promising neuroprotectors.

show abstract

Section: Belenichev Et Al 2020mentioning

confidence: 90%

Section: Possible Pathways For Activation Of Hsp70-dependent Mechanis...mentioning

confidence: 99%

Involvement of heat shock proteins HSP70 in the mechanisms of endogenous neuroprotection: the prospect of using HSP70 modulators

Беленичев

Aliyeva

Popazova

et al. 2023

Front. Cell. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Adverse effects were limited to transient febrile events that resolved on discontinuation of the drug. Preclinical studies in human neutrophils and whole blood demonstrated an immunomodulatory mode of action [47], suggesting that immunomodulatory peptide-based drugs can be safe and effective. Glutoxim is currently undergoing phase III clinical trials in the USA as a chemotherapy adjuvant (http://www.clinicaltrials.gov/ct2/ show/NCT00347412) in non-small-cell lung cancer rather than as an anti-infective, possibly because of the relatively low incidence of tuberculosis in the USA and lesser potential for return on investment.…”

Section: Reviewmentioning

confidence: 99%

Potential of immunomodulatory host defense peptides as novel anti-infectives

Easton

Nijnik

Mayer

et al. 2009

Trends in Biotechnology

197

163

View full text Add to dashboard Cite

A fundamentally new strategy for the treatment of infectious disease is the modulation of host immune responses to enhance clearance of infectious agents and reduce tissue damage due to inflammation. Antimicrobial host defense peptides have been investigated for their potential as a new class of antimicrobial drugs. Recently their immunomodulatory activities have begun to be appreciated. Modulation of innate immunity by synthetic variants of host defense peptides, called innate defense regulators (IDRs), is protective without direct antimicrobial action. We discuss the potential and current limitations in exploiting the immunomodulatory activity of IDRs as a novel anti-infective pathway. IDRs show significant promise and current research is uncovering mechanistic information that will aid in the future development of IDRs for clinical use.

show abstract

“…Several other immune response modifiers that target different stages of innate immunity and might be useful for plague therapy have recently been reviewed (Amlie- Lefond et al, 2005;Masihi, 2000), but only one, glutoxim, a sulfur-containing hexapeptide with an immunomodulatory effect on lymphocytes (Fimiani et al, 2002), has been used in an animal model of plague (Zhemchugov, 2004). When injected into mice (12?5 mg per animal) 6 h before challenge with 10 LD 50 of the virulent Y. pestis strain 231, it protected half of the animals from death.…”

Section: Antibiotic Prophylaxis and Therapymentioning

confidence: 99%