allopurinol and Coronavirus-Infections

In light of the recent pandemic, favipiravir (Avigan

Topics: Aldehyde Oxidase; Amides; Antiviral Agents; Biotransformation; Coronavirus Infections; COVID-19; Drug Interactions; Humans; Hyperuricemia; Kidney; Kidney Diseases; Molecular Structure; Organic Anion Transport Protein 1; Organic Anion Transporters; Organic Anion Transporters, Sodium-Independent; Organic Cation Transport Proteins; Pandemics; Pneumonia, Viral; Pyrazines; Uric Acid; Xanthine Oxidase

Topics: Adolescent; Allopurinol; Anemia, Hemolytic, Autoimmune; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Betacoronavirus; Combined Modality Therapy; Coronavirus Infections; COVID-19; Cytokine Release Syndrome; Daunorubicin; Fluid Therapy; Humans; Male; Methylprednisolone; Nitriles; Pandemics; Pneumonia, Viral; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Pyrazoles; Pyrimidines; Respiration, Artificial; Respiratory Distress Syndrome; SARS-CoV-2; Vincristine

To assess relationships between xanthine oxidase (XOD) and nephropathogenic infectious bronchitis virus (NIBV) infection, 240 growing layers (35 days old) were randomly divided into two groups (infected and control) of 120 chickens each. Each chicken in the control and infected group was intranasally inoculated with 0.2 mL sterile physiological saline and virus, respectively, after which serum antioxidant parameters and renal XOD mRNA expression in growing layers were evaluated at 8, 15 and 22 days post-inoculation (dpi). The results showed that serum glutathione peroxidase and superoxide dismutase activities in the infected group were significantly lower than in the control group at 8 and 15 dpi (p < 0.01), while serum malondialdehyde concentrations were significantly higher (p < 0.01). The serum uric acid was significantly higher than that of the control group at 15 dpi (p < 0.01). In addition, the kidney mRNA transcript level and serum activity of XOD in the infected group was significantly higher than that of the control group at 8, 15 and 22 dpi (p < 0.05). The results indicated that NIBV infection could cause the increases of renal XOD gene transcription and serum XOD activity, leading to hyperuricemia and reduction of antioxidants in the body.

Topics: Animals; Antioxidants; Chickens; Coronavirus Infections; Female; Infectious bronchitis virus; Kidney; Poultry Diseases; Real-Time Polymerase Chain Reaction; RNA, Messenger; Transcription, Genetic; Uric Acid; Xanthine Oxidase

We have shown that mice infected with mouse hepatitis virus A59 develop autoantibodies (autoAb) to liver and kidney fumarylacetoacetate hydrolase (FAH). Because it has been proposed that the immune system is stimulated by alarm signals called damage-associated molecular patterns or alarmins, we investigated the participation of uric acid and high-mobility group box protein 1 (HMGB1) in the autoimmune response elicited by mouse hepatitis virus (MHV). Mice subjected to MHV infection had increased plasmatic uric acid concentration that significantly decreased after 20 days of daily treatment with allopurinol and, simultaneously, autoAb to FAH were undetected. Furthermore, this autoAb disappeared after 30 days of treatment with ethyl pyruvate, along with a substantial reduction in serum HMGB1 concentration. Both results indicated a remarkable relationship between the autoimmune process induced by the virus and uric acid and HMGB1 liberation. Unexpectedly, it was found that allopurinol and ethyl pyruvate inhibited the release of both uric acid and HMGB1. Because HMGB1 is activated through binding to interleukin 1β, and that this cytokine is produced by the NLRP3 inflammasome that could be stimulated by uric acid, we propose that both alarmins could be acting in concert with the induction of the autoAb to FAH in MHV-infected mice.

Topics: Allopurinol; Animals; Autoantibodies; Autoimmunity; Coronavirus Infections; Female; Hepatitis, Viral, Animal; HMGB1 Protein; Hydrolases; Liver; Mice; Mice, Inbred BALB C; Murine hepatitis virus; NF-kappaB-Inducing Kinase; p38 Mitogen-Activated Protein Kinases; Protein Serine-Threonine Kinases; Pyruvates; Signal Transduction; Uric Acid