Abstract

Background: A recent study has indicated the potential of metformin therapy for lupus in animal models, but there has been no study evaluating the effect on pristane-induced lupus. This study aims to evaluate the effect of intraperitoneal versus oral metformin on interferon (IFN)-γ levels and FOXP3 mRNA expression on pristane-induced female BALB/c mice. Methods: In total, 31 female BALB/c mice, aged 6 weeks, were intraperitoneally induced with 0.5 ml of pristane (2,6,10,14-tetramethylpentadecane). After 120 days, the mice were grouped and treated with various treatments: normal saline 100 MCL, oral metformin 100mg/kg-BW, or intraperitoneal metformin 100mg/kg-BW. After 60 days of treatment, all treatment groups were sacrificed, and kidney specimens prepared and stained using hematoxylin and eosin. Results: IFNγ levels of saline controls vs. oral metformin group was 309.39 vs. 292.83 pg/mL (mean difference 16.56 pg/mL; 95% CI 0.74-32.37; p=0.042), and saline control vs. intraperitoneal metformin group was 309.39 vs. 266.90 pg/mL (mean difference 42.49 pg/mL; 95% CI 29.24-55.73 pg/mL; p<0.001). FOXP3 mRNA expression changes in saline controls vs. oral metformin group was 6.90 vs. 7.79-fold change (mean difference -0.89-fold change; 95% CI -1.68-(-0.11); p=0.03) and in saline controls vs. intraperitoneal metformin group was 6.90 vs. 9.02-fold change (mean difference -2.12-fold change; 95% CI -2.99-(-1.25); p=<0.001). Correlation analysis of FOXP3 mRNA expression and IFNγ level changes revealed a Pearson correlation of -0.785 (p=0.001) and R2 value of 0.616 (p=0.001). Conclusion: Metformin is a potential new therapy to reduce the levels of IFNγ and increase FOXP3 mRNA expression in mice models of systemic lupus erythematosus.

Highlights

  • Systemic lupus erythematosus (SLE) is a complex systemic disease, which is defined by multiple organ damage and dysfunction resulting from auto-antibody generation and inherited immune system dysregulation[1]

  • Metformin is a potential new therapy to reduce the levels of IFNγ and increase FOXP3 mRNA expression in mice models of systemic lupus erythematosus

  • This study aims to evaluate the effect of intraperitoneal versus oral metformin in decreasing IFNγ and increasing FOXP3 mRNA expression levels on pristane-induced female BALB/c mice, as there no studies that have evaluated the route of metformin delivery, especially on an environmentally induced model of lupus nephritis

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Summary

Introduction

Systemic lupus erythematosus (SLE) is a complex systemic disease, which is defined by multiple organ damage and dysfunction resulting from auto-antibody generation and inherited immune system dysregulation[1]. Lupus treatment currently relies on immunosuppressants and corticosteroids to suppress the immune system and reduce disease activity. This strategy is not ideal; there are several types of patients who do not respond well to immunosuppression and this therapy produces side effects, such as recurrent infection, bone density loss, sarcopenia and psychological disturbances. This study aims to evaluate the effect of intraperitoneal versus oral metformin on interferon (IFN)-γ levels and FOXP3 mRNA expression on pristaneinduced female BALB/c mice. FOXP3 mRNA expression changes in saline controls vs oral metformin group was 6.90 vs 7.79fold change (mean difference -0.89-fold change; 95% CI -1.68-(-0.11); p=0.03) and in saline controls vs intraperitoneal metformin group was 6.90 vs 9.02-fold change

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