Therapeutic benefits of Indole-3-Carbinol in adjuvant-induced arthritis and its protective effect against methotrexate induced-hepatic toxicity

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.

The role of resveratrol in hepatotoxicity caused by methotrexate

“…Our data will be applicable as anatomical base to study the LM diameter, CR, CC diameter and DV diameter of the rabbit adrenal glands, because this animal species is considered as a pet wand at the same time is predisposed for adrenal glands diseases. Our attitude correspond to the data for the importance of the knowledge for the normal measurements of the glands (3,4).…”

“…Methotrexate (Mtx), a folic acid antagonist, is one of antiinflammatory, immunosuppressive, antiproliferative, antioxidant and cytotoxic agent that effectively reduces cellular growth and is widely used in the treatment of several diseases, including: ectopic pregnancy, rheumatoid arthritis, leukemia, systemic lupuserythematosus, psoriasis neoplastic diseases (1)(2)(3)(4).…”

“…It has many application fields as a therapeutic agent at low doses in autoimmune diseases and at high doses in many malignancies. Despite of wide usage, Mtx has a range of side effects such as hepatotoxicity -nephrotoxicity (4,(6)(7)(8)(9). Therefore, it has been advised to prevent Mtx induced hepatotoxicity, it is using concomitant with antioxidants (10).…”

Indole-3-carbinol inhibits the proliferation of colorectal carcinoma LoVo cells through activation of the apoptotic signaling pathway

“…41 Thus, natural compounds with limited side effects are potential alternative therapeutic agents for cancer. 42 I3C is a phytochemical found in cruciferous vegetables. 43 Various studies have reported the therapeutic effects of I3C, such as cancer-preventive, anti-inflammatory, and anti-oxidative effects.…”

Preoperative Management of Surgical Patients Using Dietary Supplements

“…Has been found to inhibit arthritis in mice without concomitant hepatotoxic effects 82 as well as to decrease cholesterol levels and limit obesity. No human safety data.…”