Current treatment modalities are fraught with significant side effects

Current treatment modalities are fraught with significant side effects. age of 17?weeks. MRL-MpJ mice develop lupus-like disease around 47?weeks and typically die at 73?weeks. Six mice of Rabbit Polyclonal to CSTL1 each strain received autoclaved water only (mice by significantly reducing lymphoproliferation, proteinuria, lesions (tail) and autoantibodies. mice as an animal model of SLE/SS MRLmice resemble human SLE in several ways, and therefore, is a widely used animal model.9C18 MRL-mouse has a single-gene mutation (apoptosis gene on mouse chromosome 19, and therefore, a defect in apoptotic death of lymphocytes. There is massive accumulation of CD4?CD8? T lymphocytes and development of a disease similar to human SLE. Even though lymphoproliferation in human lupus is not as prominent in majority, other features like lupus nephritis, skin lesions, arthritis and neurological manifestations match well. However, lymphadenopathy with double-negative T-cell proliferation may mimic the defective apoptotic mechanisms and its clearance in human lupus. MRLmice develop salivary and lacrimal gland lymphocytic infiltrates similar to human SS, but without functional loss.13C15 MRL-MPJ mice MRL/MpJ mice, even though they have the normal gene, develop autoimmune symptoms much later than the MRL-mice. MRL/MpJ inbred female mice have a lifespan of 73?weeks, while males live for 93?weeks. (3β,20E)-24-Norchola-5,20(22)-diene-3,23-diol MRL-female mice typically die at 17?weeks of age while the males die at 22?weeks. MRL-MpJ mice serve as a control for the MRL-mice ( The aetiology of SLE/SS is largely unknown. There is no effective treatment for SLE/SS, other than immunosuppressives. Current treatment modalities are fraught with significant side effects. Therefore, it is paramount to have studies that can identify new therapeutic agents with few side effects. Ultrasoluble curcumin Our studies showing significantly increased oxidative damage in lupus patients19C21 led us to investigate an antioxidant/anti-inflammatory agent known as curcumin,22C31 obtained from the rhizome of (turmeric). Curcumin (1,7-bis[4-hydroxy-3-methoxyphenyl]-1,6-heptadiene-3,5-dione), a naturally occurring nutraceutical, comprises 4C6% of turmeric. Commercial curcumin contains curcumin compound (77%), demethoxycurcumin (DMC) (17%) and bisdemethoxycurcumin (BDMC) (3%). Curcumin, when abbreviated CU, will refer to the commercially available mixture containing all?three curcuminoid compounds. CU has (3β,20E)-24-Norchola-5,20(22)-diene-3,23-diol been studied in prostate, oesophagus, lung, breast and oral cancers.32C35 Recently, CU was shown to suppress nuclear factor-kB and increase apoptosis in both Flo-1 and OE33 oesophageal adenocarcinoma cell lines36 37 CU also induces release of cytochrome or MpJ mice each. Materials and methods Materials Curcumin was purchased from Sigma Chemical Co., St Louis, Missouri, USA. Turmeric was bought from a local grocery store. Autoantigens Sm and ribonucleoprotein (RNP) were from Immunovision, AK. HEp-2 antinuclear antibody (ANA) (3β,20E)-24-Norchola-5,20(22)-diene-3,23-diol assay kit and anti-double-stranded DNA (anti-dsDNA) assay kit were from INOVA Diagnostics, San Diego, California, USA. Accustrip URS 10 Urine Reagent Strips were from Jant Pharmacal Corporation, Encino, California, USA. Secondary antibody conjugates were from Jackson Laboratories, Bar Harbor, Maine, USA. All other chemicals were of reagent grade. Animals MRL-and MRL-MpJ mice were purchased from Jackson Laboratories (Bar Harbor, Massachusetts, USA). Animals were housed in the OMRF Laboratory Animal Resource Center of the Oklahoma Medical Research Foundation with a 12?h light/dark cycle. Mice were fed standard -irradiated mouse chow (Picolab Rodent Diet 20, LabDiet, St. Louis, Missouri, USA) and water ad libitum. For mice selected for curcumin or turmeric treatment, heat/pressure solubilised curcumin or turmeric was supplied in the water bottle. All experimental designs were approved by the OMRF Institutional Animal Care and Use Committee according to established guidelines. Curcumin and turmeric solubilisation CU and TU were heat-solubilised/pressure-solubilised at 5?mg/mL water (UsC and UsT) and supplied to mice in water bottle. CU, at 5?mg/mL ultrapure water, was heated to boiling in an aluminium foil-covered conical flask on a hot plate for 1?h and autoclaved for 30?min. The heat-solubilised/pressure-solubilised CU was filtered with Whatman #1 filter after cooling. This filtrate (UsC) was supplied to mice in the water bottle. TU, at 5?mg/mL ultrapure water, was heated to boiling on a hot plate for 1?h and centrifuged at 5000?for 20?min after cooling. The supernatant (UsT) was provided to (3β,20E)-24-Norchola-5,20(22)-diene-3,23-diol the mice in the.

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