Abstract
BackgroundRheumatoid arthritis (RA) being an incapacitating disease requires early effective intervention. Considering Methotrexate (MTX)- the first line of treatment for RA- intoxicates the liver; therefore, alternative therapies with similar efficacy yet lower cytotoxicity are desired. Indole-3-Carbinol (I3C) which is found in cruciferous vegetables was examined for its possible therapeutic potentials in comparison with MTX by investigating its anti-inflammatory, anti-arthritic, anti-oxidant, and hepatoprotective potentials in adjuvant-induced arthritis (AIA) rat model.MethodsArthritis was induced in Sprague Dawley rats by injection of Complete Freund’s Adjuvant (CFA). Arthritic rats were treated with I3C and/or MTX. To examine the anti-inflammatory and anti-arthritic effect, the following parameters were assessed: body weight, macroscopic scoring of the hind paw, the level of the pivotal cytokines (TNF-α, IL-6) heavily involved in the pathogenesis, spleen index, and erythrocyte sedimentation rate. At a histological level, the tibiotarsal joint was stained with several specific stains. To assess the hepatoprotective and anti-oxidant effects, several oxidative stress parameters were monitored, and the liver histology was examined.ResultsBoth I3C and MTX attenuated the inflammation that was aggravated by arthritis by downregulating the inflammatory markers and mediators and alleviating the histopathological changes affecting the tibiotarsal joint. I3C attenuated the liver impairment that was initiated by arthritis and MTX treatment. It did so by downregulating the pro-oxidants and up-regulating the anti-oxidant defenses and by reducing the pathological changes affecting the liver.ConclusionOur results suggest that I3C is as potent as MTX as an anti-inflammatory and anti-arthritic agent. In addition, I3C does so while protecting the liver from damage as opposed to MTX.
Highlights
Rheumatoid arthritis (RA) being an incapacitating disease requires early effective intervention
The groups used are as follows: a) a normal group injected subcutaneously with saline into the left footpad, b) a normal group injected subcutaneously with saline into the left footpad which received the vehicle used to dissolve I3C (10% Dimethyl sulfoxide (DMSO), 10% Tween 80, 80% sucrose), c) a group injected with Complete Freund’s Adjuvant (CFA) that received no treatment, d) a group injected with CFA that received MTX (2 mg/kg/week for 6 weeks intraperitoneally), e) a group injected with CFA that received I3C (100 mg/kg/day for 3 weeks by diet) f) group injected with CFA that received both MTX (2 mg/kg/week for 6 weeks intraperitoneally) and I3C (100 mg/kg/day for 3 weeks by diet)
The body weight of arthritic non-treated model group rats declined from day 2 to 22 compared to normal rats and these rats showed a gradual increase in the inflammation and erythema which were evident as increased macroscopic score with a peak of score 4 on day 22
Summary
Rheumatoid arthritis (RA) being an incapacitating disease requires early effective intervention. Considering Methotrexate (MTX)- the first line of treatment for RA- intoxicates the liver; alternative therapies with similar efficacy yet lower cytotoxicity are desired. Rheumatoid Arthritis (RA) is a progressive, chronic, autoimmune disease that is associated with inflammation affecting the lining of the joints, articular cartilage and bones. Methotrexate (MTX) which is an antimetabolite and a DMARD is generally recognized as the first-line treatment for RA. That efficacy is hindered by the adverse effects it generates on the liver, rendering compliance to the treatment negligible. The toxic effects of MTX are suggested to be due to the accumulation of methotrexate polyglutamates in the liver resulting in the depletion of hepatic folate stores and inhibiting purine and pyrimidine precursor synthesis. Complementary and alternative natural agents are desired and strongly recommended
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