Application of arsenic trioxide for the treatment of lupus nephritis
Bor-Luen,Chiang Graduate Institute of Clinical Medicine
Arsenic trioxide has been used therapeutically for approximately 2,400 years as apartof Chinese medicine. It is historically the poison and most common side effectsaregastrointestinal and most inorganic arsenic after ingestion is eliminated rapidly inthe urine. Arsenic trioxide has many effects on cells. It can not only induce apoptosis, butalso has anti-proliferative activity. It even can inhibit angiogenesis. However, ithas different mechanisms to control these effects. Arsenictrioxide may interact with targeted proteins which contain closely spaced cysteine residues. Arsenic trioxide may alter the function of several enzymes and moleculesof cell signaling, such as AP-1 andresult in increasing downstream molecule activity. Inflammatory signal transduction was also blocked by arsenic trioxide,which can inhibit IKK, which is required for activation of the proinflammatory transcription factor NF-kB. Intherapy, arsenic trioxide is currently FDA-approved for treating chronic or acute leukemias. It is also used in clinical trials to evaluate its efficacy for treating multiple myeloma and a variety of solid tumors. In this proposal, we like to establish an animal model of lupus for the study of Chinese traditional drugs.
We treated NZB/NZW F1 (BWF1) lupus prone mice intrperitoneally with different dose of arsenic trioxide three times a week for three months. The effects of arsenic trioxide on the level of autoanibody against double-stranded DNA (dsDNA) or single-stranded DNA (ssDNA) and interlukin-10 (IL-10) in serum were detected by ELISA,the severe glomerulonephritis (GN) was determined by multistix, the renal histopathology was observed by immunofluorescence, and the change of peripheral lymphocytes subpopulation was analyzed by flow cytometry.
Administration of arsenic trioxide decreased the level of anti-dsDNA antibody in lupus mice. In addition, alleviation of proteinuria and prolonged life span was also noted in the mice receiving arsenic trioxide treatment. Furthermore, we also found that the percentage of peripheral T cells increased; however, the percentage of B cells in peripheral blood decreased significantly after treatment and so did the level of IL-10 in serum.
Arsenic trioxide can decreases anti-dsDNA antibody level and alleviates disease severity of lupus mice. We believe the result here will provide an excellent model to study the therapeutic effect of Chinese traditional drugs, such as arsenic trioxide, on the disease development of lupus in the future.
Key Word :Systemic lupus erythematosus, arsenic trioxide, nephritis