Effect of Pioglitazone on Antioxidant Capacity and Oxidative Damage after Spinal Cord Injury in Rat

BACKGROUND AND OBJECTIVE: Reduction of the antioxidant capacity and oxidative damage has a crucial role in development of damage after spinal cord injury. Since pioglitazone (PPAR-gamma agonist) have a powerful antioxidant property, the present study aimed to evaluate the effect of pioglitazone on antioxidant capacity and oxidative damage in the injured areas of spinal cord in rat. METHODS: In the present experimental study eighteen male Wistar rats divided into three groups as follow (n=6); sham, control injured and pioglitazone-treated injured group. Spinal cord injury was performed according to the Ping-Weight Drop (contusion) model in rat. The animals received pioglitazone (3 mg/kg) intraperitoneally at times of 15 min after injury and then each 12 hours until a week. At the end, malondialdehyde level, activity of catalase and superoxide dismutase (SOD) enzymes and also histopathological alterations of spinal cord were assessed. FINDINGS: Induction of spinal cord injury in control injured animals significantly increased the malondialdehyde levels (56%) and decreased the activity of catalase (48%) and SOD (65%) enzymes compared to sham group (p=0.004, p=0.001 and P=0.008, respectively). Pioglitazone in treated injured group significantly decreased the malondialdehyde levels (38%) and increased the activity of catalase (34%) enzyme compared to control injured group (p=0.038 and p=0.014, respectively). Also, pioglitazone prevented the histopathological changes of injured areas in spinal cord. CONCLUSION: The findings of present study indicate that treatment with pioglitazone through potentiation of the antioxidant defense capacity of injured spinal cord decreases oxidative damage and also histopathological changes of spinal cord

Pharmacological mechanism of immunomodulatory agents for the treatment of severe cases of COVID-19 infection

Objective: Coronavirus disease 2019 (COVID-19) is a world-wide pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To date, treatment of severe COVID-19 is far from clear. Therefore, it is urgent to develop an effective option for the treatment of patients with COVID-19. Most patients with severe COVID-19 exhibit markedly increased serum levels of pro-inflammatory cytokines, including interferon (IFN)-α, IFN-γ, and interleukin (IL)-1β. Immunotherapeutic strategies have an important role in the suppression of cytokine storm and respiratory failure in patients with COVID-19. Methods: A systematic search in the literature was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, as well as Google Scholar preprint database using all available MeSH terms for Coronavirus, SARS-CoV-2, anti-rheumatoid agents, COVID-19, cytokine storm, immunotherapeutic drugs, IFN, interleukin, JAK/STAT inhibitors, MCP, MIP, TNF. Results: Here, we first review common complications of COVID-19 patients, particularly neurological symptoms. We next explain host immune responses against COVID-19 particles. Finally, we summarize the existing experimental and clinical immunotherapeutic strategies, particularly anti-rheumatoid agents and also plasma (with a high level of gamma globulin) therapy for severe COVID-19 patients. We discuss both their therapeutic effects and side effects that should be taken into consideration for their clinical application. Conclusion: It is suggested that immunosuppressants, such as anti-rheumatoid drugs, could be considered as a potential approach for the treatment of cytokine storm in severe cases of COVID-19. One possible limitation of immunosuppressant therapy is their inhibitory effects on host anti-viral immune response. So, the appropriate timing of administration should be carefully considered. © 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature