How does ARA-290 work to protect DNA?

RNA extraction

Researchers have demonstrated that ARA-290 has antigenotoxic, antioxidant, anti-inflammatory, and antiapoptotic activities. There is a correlation between ARA-290 concentration and its genoprotective effects. Several cell lines treated with doxorubicin benefited from ARA-290’s genoprotective properties. Based on these findings, it is hypothesized that ARA-290 may function as a protective agent, protecting against DOX-induced DNA damage and oxidative stress.

The nonhematopoietic peptide ARA-290, created from EPO, binds preferentially with the innate repair receptor and has comparable properties. Unlike EPO, which has undesirable hematological side effects, ARA-290 is clinically helpful in protecting tissues without these drawbacks.

The substantial hematological side effects, notably the cardiovascular adverse effects of EPO, restrict its potential therapeutic applicability, although ARA-290 mediates tissue protection without these drawbacks. Mechanistically, ARA-290 exerts anti-inflammatory and antiapoptotic. Tissue-protective effects interact with the innate repair receptor (IRR) and thereby inhibit the activation of pro-inflammatory pathways, glycogen synthase kinase-3, p38 mitogen-activated protein kinase, and nuclear factor-kappaB-driven gene transcription. All of these result in the phosphorylation of endothelial. Furthermore, some investigations have demonstrated that the Janus kinase-2 (JAK-2) pathway is the hypothesized cytoprotective pro-survival mechanism of the ARA-290. The phosphorylation of JAK-2 and the pathways it activates have potent anti-inflammatory and antiapoptotic effects. Furthermore, ARA-290’s cumulative preclinical toxicology tests have shown no safety concerns. Here, researchers test if ARA-290 has a genoprotective effect for the first time.

Researchers hypothesized that, by moderating the cytotoxicity, genotoxicity, and oxidative stress caused in vitro by DOX, ARA-290 would serve as a chemoprotective substance, and that is what researchers set out to test in the current work.

Protects healthy cells without impeding the effectiveness of doxorubicin in killing cancer cells

Secondary malignancies, such as leukemia, are more common after chemotherapy than radiation treatment. Free-radical scavenging properties of antioxidants [restricted to normal, non-cancerous cells] may prevent the systemic oxidative stress caused by chemotherapy, which plays a significant role in the development of cytotoxicity and carcinogenesis in normal tissues.

The research results demonstrated that ARA-290 safeguards healthy cells without affecting the efficacy of  DOX against cancer. Previous research has shown that EpoR transcript levels are 10-1000-fold lower in tumor tissues and cell lines compared to normal cells, suggesting that functional EpoR is not expressed in tumor cells.

ARA-290’s Effect on Normal Cellular Oxidative Stress (ROS):

Intervention with ARA-290 reduced oxidative stress and reactive oxygen species production. Antioxidant enzyme activities, including GPx and SOD, were elevated in response to ARA-290 treatment, as shown by the current research. This suggests that ARA-290 could help alleviate the symptoms of stress-related free radical generation.

Both pro-inflammatory and anti-inflammatory cytokines are elevated, and immune cells infiltrate the brain after a brain injury. EPO’s anti-inflammatory effects were shown by its ability to lessen the infiltration and activation of immune/inflammatory cells such as neutrophils and microglial cells. One possible justification for employing this paradigm is the rapid rise in inflammatory cytokine concentrations after the induction of brain damage in rats. 

Demyelinating inflammatory diseases of the peripheral nervous system have a model organism in experimental autoimmune neuritis, a T-cell model triggered by autoantigens. Breakdown of the blood-nerve barrier, increased reactive T cells and macrophages, and demyelination are all hallmarks of experimental autoimmune neuritis. Researchers revealed that EPO might reduce inflammation and improve Schwann cell function, which can help alleviate autoimmune neuritis. Animal models of inflammatory demyelinating polyneuropathies, such as experimental autoimmune neuritis, allow researchers to examine the potential effects of new therapeutics before they are tested on humans. Buy ARA-290 peptide if you are a researcher.