Dataset Information

The Effects of H₂S and Recombinant Human Hsp70 on Inflammation Induced by SARS and Other Agents In Vitro and In Vivo.

ABSTRACT: The ongoing epidemic caused by SARS-CoV-2 infection led to the search for fundamentally new ways and means to combat inflammation and other pathologies caused by this virus. Using a cellular model of lipopolysaccharide (LPS)-induced sepsis (human promonocytes), we showed that both a hydrogen sulfide donor (sodium thiosulfate, STS) and a recombinant Heat shock protein 70 (rHsp70) effectively block all major inflammatory mediators when administrated before and after LPS challenge. The protective anti-inflammatory effect of rHsp70 and H₂S was also confirmed in vivo using various animal models of pneumonia. Specifically, it was found that rHsp70 injections prevented the development of the acute respiratory distress syndrome in highly pathogenic pneumonia in mice, increased animal survival, and reduced the number of Programmed death-1 (PD-1)-positive T-lymphocytes in peripheral blood. Based on our model experiments we developed a combined two-phase therapeutic approach for the treatment of COVID-19 patients. This procedure includes the inhalation of hot helium-oxygen mixtures for induction of endogenous Hsp70 in the first phase and STS inhalation in the second phase. The use of this approach has yielded positive results in COVID-19 patients, reducing the area of lung lesions, restoring parameters of innate immunity and T-cell immune response against coronavirus infection, and preventing the development of pulmonary fibrosis and immune exhaustion syndrome.

SUBMITTER: Onikienko S

PROVIDER: S-EPMC9496158 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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The Effects of H<sub>2</sub>S and Recombinant Human Hsp70 on Inflammation Induced by SARS and Other Agents In Vitro and In Vivo.

Onikienko Sergei S Vinokurov Maxim M Yurinskaya Marina M Zemlyanoi Alexander A Abkin Sergei S Shaykhutdinova Elvira E Palikov Victor V Ivanov Alexander A Smirnova Olga O Fedyakina Irina I Bychkova Natalia N Zatsepina Olga O Garbuz David D Evgen'ev Michael M

Biomedicines 20220901 9

The ongoing epidemic caused by SARS-CoV-2 infection led to the search for fundamentally new ways and means to combat inflammation and other pathologies caused by this virus. Using a cellular model of lipopolysaccharide (LPS)-induced sepsis (human promonocytes), we showed that both a hydrogen sulfide donor (sodium thiosulfate, STS) and a recombinant Heat shock protein 70 (rHsp70) effectively block all major inflammatory mediators when administrated before and after LPS challenge. The protective a ...[more]

PMID: 36140256

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Project description:Toxicity assessment for regulatory purposes is starting to move away from traditional in vivo methods and towards new approach methodologies (NAM) such as high-throughput in vitro models and computational tools. For materials with limited hazard information, utilising quantitative Adverse Outcome Pathways (AOPs) in a testing strategy involving NAM can produce information relevant for risk assessment. The aim of this work was to determine the feasibility of linking in vitro endpoints to in vivo events, and moreover to key events associated with the onset of a chosen adverse outcome to aid in the development of NAM testing strategies. To do this, we focussed on the adverse outcome pathway (AOP) relating to the onset of pulmonary fibrosis. We extracted in vivo and in vitro dose-response information for particles known to induce this pulmonary fibrosis (crystalline silica, specifically α-quartz). To test the in vivo-in vitro extrapolation (IVIVE) determined for crystalline silica, cerium dioxide nanoparticles (nano-CeO2) were used as a case study allowing us to evaluate our findings with a less studied substance. The IVIVE methodology outlined in this paper is formed of five steps, which can be more generally summarised into two categories (i) aligning the in vivo and in vitro dosimetry, (ii) comparing the dose-response curves and derivation of conversion factors. Our analysis shows promising results with regards to correlation of in vitro cytokine secretion to in vivo acute pulmonary inflammation assessed by polymorphonuclear leukocyte influx, most notable is the potential of using IL-6 and IL-1β cytokine secretion from simple in vitro submerged models as a screening tool to assess the likelihood of lung inflammation at an early stage in product development, hence allowing a more targeted investigation using either a smaller, more targeted in vivo study or in the future a more complex in vitro protocol. This paper also highlights the strengths and limitations as well as the current difficulties in performing IVIVE assessment and suggestions for overcoming these issues.

Dataset Information

The Effects of H₂S and Recombinant Human Hsp70 on Inflammation Induced by SARS and Other Agents In Vitro and In Vivo.

Publications

The Effects of H<sub>2</sub>S and Recombinant Human Hsp70 on Inflammation Induced by SARS and Other Agents In Vitro and In Vivo.

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Dataset Information

The Effects of H2S and Recombinant Human Hsp70 on Inflammation Induced by SARS and Other Agents In Vitro and In Vivo.

Publications

The Effects of H<sub>2</sub>S and Recombinant Human Hsp70 on Inflammation Induced by SARS and Other Agents In Vitro and In Vivo.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

The Effects of H₂S and Recombinant Human Hsp70 on Inflammation Induced by SARS and Other Agents In Vitro and In Vivo.