Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Jun 25:2018:9365464.
doi: 10.1155/2018/9365464. eCollection 2018.

Anti-Inflammatory, Antioxidative, and Hepatoprotective Effects of Trans Δ9-Tetrahydrocannabinol/Sesame Oil on Adjuvant-Induced Arthritis in Rats

Morouj Ismail  1 , Hiba Hasan  1 , Youmna El-Orfali  1 , Hanan Ismail  1 , Ghada Khawaja  1
Affiliations

Anti-Inflammatory, Antioxidative, and Hepatoprotective Effects of Trans Δ9-Tetrahydrocannabinol/Sesame Oil on Adjuvant-Induced Arthritis in Rats

Morouj Ismail et al. Evid Based Complement Alternat Med. .

Abstract

Rheumatoid arthritis (RA) is a painful chronic autoimmune disease affecting the joints. Its first-line therapy, Methotrexate (MTX), although effective in ameliorating the progress of the disease, induces hepatotoxicity over long-term usage. Thus, seeking natural compounds with fewer side effects could be an alternative therapeutic approach. This study aimed to investigate the anti-inflammatory, antiarthritic, and antioxidative effects of synthetic trans-Δ9-tetrahydrocannabinol (Δ9-THC) dissolved in sesame oil (Dronabinol) against MTX in adjuvant-induced arthritis (AIA) rat model. Daily oral administration of Δ9-THC/sesame oil, over a period of 21 days, was well tolerated in arthritic rats with no particular psychoactive side effects. It markedly attenuated the severity of clinical manifestations, recovered the histopathological changes in tibiotarsal joints, and repressed the splenomegaly in arthritic rats. Δ9-THC/sesame oil therapy showed similar effects to MTX in neutralizing the inflammatory process of AIA, through attenuating erythrocyte sedimentation rate (ESR) scores and proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin 1-beta (IL-1β), and interleukin-6 (IL-6) levels, to normal values. As opposed to MTX, this natural combination markedly protected the liver of arthritic rats and downregulated the induced oxidative stress by increasing the antioxidant defense system such as activities of catalase and superoxide dismutase (SOD) and levels of glutathione (GSH). These results suggest promising effects for the clinical use of Δ9-THC/sesame oil therapy in alleviating arthritic clinical signs as well as arthritis-induced liver injury.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Effect of treatments on left hind paw, body weight, and spleen index. (a) Macroscopic image of left hind paw at day 16 in following groups: (A) normal [N], (B) untreated AIA [A], (C) AIA treated with MTX [AM], (D) AIA treated with sesame oil [AS], and (E) AIA treated with Δ9-THC/sesame oil [AT]. (b) Mean macroscopic scores change, (c) body weight difference, and (d) spleen index among groups. All values are presented as mean ± SD of 8 rats per group. ∞∞∞∞p<0.0001 for A compared with N. ∗p<0.05, ∗∗p<0.01, ∗∗∗p<0.001, ∗∗∗∗p<0.0001 compared with A. ##p<0.01 and ####p<0.0001 compared with the positive control group AM.
Figure 2
Figure 2
Light micrographs of tibiotarsal joint sections of rat left hind paws. (a, b, c, d, e) H&E stained micrographs. (a) Normal rat shows normal appearance of the synovial membrane and cartilage. (b) AIA untreated rat shows severe synovial hyperplasia (∗∗∗) with cellular infiltration (###). (c) MTX-treated AIA rat shows moderate synovial hyperplasia (∗∗) and minimal infiltration (#). (d) Sesame oil-treated AIA rat shows severe synovial hyperplasia (∗∗∗) with some infiltration (##). (e) Δ9-THC/sesame oil-treated AIA rat shows minimal synovial hyperplasia (∗) with no infiltration. B: bone, C: cartilage, S: synovium. (f, g, h, i, j) Masson's Trichrome stained micrographs. (f) Normal rat shows normal and intact cartilage. (g) AIA untreated rat shows severe cartilage calcification (¤¤¤). (h) MTX-treated AIA rat shows minimal cartilage calcification (¤). (i) Sesame oil-treated AIA rat shows severe cartilage calcification (¤¤¤). (e) Δ9-THC/sesame oil-treated AIA rat shows moderate cartilage calcification (¤¤). (Original magnification x40.)
Figure 3
Figure 3
Effect of treatments on inflammatory markers. (a) Blood ESR, serum, (b) TNF-α, (c) IL-1β, and (d) IL-6 among groups. All values are presented as mean ± SD of 8 rats per group. ∞∞∞∞p<0.0001 for A compared with N. ∗∗p<0.01, ∗∗∗p<0.001, ∗∗∗∗p<0.0001 compared with arthritic group A. #p<0.05, ###p<0.001 compared with positive control group AM. ≈≈p<0.01 between AS and AT.
Figure 4
Figure 4
Effect of treatments on liver histology. Photomicrographs of liver sections stained by H&E. (a) Normal rat showing normal liver architecture. (b) AIA untreated rat showing moderate portal inflammation (+++) and neutrophil infiltration (black arrow). (c, d) MTX-treated AIA rat shows distortion of liver architecture with severe portal inflammation (++++) and neutrophil infiltration (black arrow), vascular congestion (aster), and multinucleation (cross). (e) Sesame oil-treated AIA rat shows mild portal inflammation (++) with neutrophil infiltration (arrow). (f) Δ9-THC/sesame oil-treated AIA rat shows minimal portal inflammation (+) with neutrophil infiltration (arrow) and normal liver architecture.
Figure 5
Figure 5
Effect of treatments on liver function enzymes. (a) ALT and (b) AST serum activity levels among groups. All values are presented as mean ± SD of 8 rats per group. ∞∞∞∞p<0.001 for A compared with N. ∗p<0.05, ∗∗∗∗p<0.0001 compared with arthritic group A. ####p<0.0001 compared with positive control AM.
Figure 6
Figure 6
Effect of treatments on liver oxidative stress and antioxidative defense biomarkers. (a) Lipid peroxidation levels (MDA); enzymatic activities of (b) catalase, (c) SOD, and (d) glutathione levels liver homogenates. All values are presented as mean ± SD of 8 rats per group. ∞p< 0.05, ∞∞p<0.01, and ∞∞∞∞p<0.0001 for A and/or AM compared with N. ∗∗∗p<0.001, ∗∗∗∗p<0.0001 compared with arthritic group A. ##p<0.01, ####p<0.0001 compared with positive control AM. ≈≈≈≈p<0.0001 between AS and AT.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Scott D. L., Wolfe F., Huizinga T. W. J. Rheumatoid arthritis. The Lancet. 2010;376(9746):1094–1108. doi: 10.1016/S0140-6736(10)60826-4. - DOI - PubMed
    1. Kumar L. D., Karthik R., Gayathri N., Sivasudha T. Advancement in contemporary diagnostic and therapeutic approaches for rheumatoid arthritis. Biomedicine & Pharmacotherapy. 2016;79:52–61. doi: 10.1016/j.biopha.2016.02.001. - DOI - PubMed
    1. Choy E. Understanding the dynamics: Pathways involved in the pathogenesis of rheumatoid arthritis. Rheumatology. 2012;51(supplement 5): v3–v11. doi: 10.1093/rheumatology/kes113. - DOI - PubMed
    1. Müller-Ladner U., Pap T., Gay R. E., Neidhart M., Gay S. Mechanisms of disease: the molecular and cellular basis of joint destruction in rheumatoid arthritis. Nature Clinical Practice: Rheumatology. 2005;1(2):102–110. doi: 10.1038/ncprheum0047. - DOI - PubMed
    1. Kamanli A., Naziroğlu M., Aydilek N., Hacievliyagil C. Plasma lipid peroxidation and antioxidant levels in patients with rheumatoid arthritis. Cell Biochemistry & Function. 2004;22(1):53–57. doi: 10.1002/cbf.1055. - DOI - PubMed