Anti-Hepatotoxic and Synergistic Effects of Sesame Oil With Methotrexate in Adjuvant Induced Arthritis

Abstract

Methotrexate (MTX) is the first-line agent for rheumatoid arthritis (RA) treatment although it causes hepatotoxicity leading to poor compliance to therapy. Sesame oil is unique due to its unusually high oxidative stability and anti-inflammatory property that attributed mainly to the presence of α-tocopherol and anti-oxidative sesame lignans. These components give sesame oil extraordinary high oxidative stability and anti-inflammatory property. The present study aimed to investigate the anti-hepatotoxic and therapeutic potential of sesame oil alone or in combined therapy with MTX on RA rat model. Assessment of RA performed by measuring paw volume, rheumatoid factor and anti-cycliccitrullinated peptide antibody. Biomarkers of cartilage degeneration (MMP-3) and synthesis, (IGF-1), inflammatory mediators (TNF-α, IL-6, NO), anti-inflammatory mediators(IL-10) and oxidative stress were estimated. MTX mono-therapy were enhanced hepatotoxicity but concomitant administration with sesame oil was able to ameliorating RA biomarker and led to an increase its effectiveness without hepatotoxicity. Therefore combined therapy of MTX with sesame oil may lead to synergistic anti-arthritic action with fewer side effects of MTX on liver.

A systematic review on antioxidant and antiinflammatory activity of Sesame (Sesamum indicum L.) oil and further confirmation of antiinflammatory activity by chemical profiling and molecular docking

“…A number of reports stated that SO showed the antiinflammatory effect through reduction of proinflammatory cytokines (e.g., TNF‐α, IL‐6, IL‐1α, and IL‐1β) as well as antioxidative effect either reduction of ROS or induction of antioxidative enzymes (GSH, NADPH oxidase, and GPx; Hsu, Chu, & Jou, b; Hsu, Chu, Li, & Liu, ; Kang, Naito, Tsujihara, & Osawa, ; Nakano et al, ; Narasimhulu et al, ; Narasimhulu, Riad, & Parthasarathy, ; Figure ). Ali, Atia, El Allawy, and Alla () showed that SO significantly decreased the levels of inflammatory mediator TNF‐α and IL‐6, although the levels of antiinflammatory mediator IL‐10 were significantly amplified in groups treated with combination of SO with MTX (first line antiarthritis agent) compared with group treated with SO only or MTX only in adjuvant‐induced arthritis rat model (Ali et al, ). Later, Ismail, Hasan, El‐Orfali, Ismail, and Khawaja () reported that daily oral administration of Δ9‐THC/SO combination, over a period of 21 days, attenuated erythrocyte sedimentation rate scores and proinflammatory cytokines, including TNF‐α, IL‐1β, and IL‐6 levels, to normal values and MTX‐treated values on adjuvant‐induced arthritis rat model (Ismail et al, ).…”

Effects of sesame (Sesamum indicum L.) and bioactive compounds (sesamin and sesamolin) on inflammation and atherosclerosis: A review

“…Oral administration of rats suffering from rheumatoid arthritis, with sesame oil (1 mL/kg) and methotrexate (MTX) (1 and 2 mg/kg) reduced IL‐6, and TNF‐α also increased the amount of IL‐10 (Ali et al, 2017). In another study, in rats suffering from rheumatoid damage induced with injection of complete Freund's adjuvant in the left foot, oral administration of dronabinol (Δ9‐THC)/sesame oil, 2.5 mg/kg for 21 days decreased the deposition of erythrocytes and inflammatory cytokines, including TNF‐α, IL‐6, and IL‐10.…”