Effect of γ-tocotrienol in Counteracting Oxidative Stress and Joint Damage in Collagen-induced Arthritis in Rats

Overview

Journal Exp Ther Med

Specialty Pathology

Date 2014 Jun 19

PMID 24940448

Citations 16

Authors

Ammu Radhakrishnan

Dulanthi Tudawe

Srikumar Chakravarthi

Gan Seng Chiew

Nagaraja Haleagrahara

Affiliations

Soon will be listed here.

Abstract

Tocotrienols exhibit a significant anti-inflammatory and antioxidant effect in numerous human diseases. However, the anti-inflammatory and antioxidant effects of tocotrienols in arthritic conditions are not well documented. Therefore, the effect of γ-tocotrienol supplementation against oxidative stress and joint pathology in collagen-induced arthritis in rats was investigated in the present study. Adult female Dark Agouti rats were randomly divided into groups: Control, γ-tocotrienol alone, arthritis alone and arthritis with γ-tocotrienol. Arthritis was induced using 4 mg/kg body weight collagen in complete Freund's adjuvant. The rats were treated orally with 5 mg/kg body weight of γ-tocotrienol between day 21 and day 45. After 45 days, serum C-reactive protein (CRP), tumor necrosis factor (TNF)-α, superoxide dismutase (SOD) and total glutathione (GSH) assays were conducted. γ-tocotrienol significantly reduced the arthritis-induced changes in body weight, CRP, TNF-α, SOD and the total GSH levels. There was a significant reduction in the arthritis-induced histopathological changes in the γ-tocotrienol treatment group. The data indicated that administration of γ-tocotrienol resulted in a significant antioxidant and anti-inflammatory effect on collagen-induced arthritis; therefore, γ-tocotrienol may have therapeutic potential as a long-term anti-arthritic agent in rheumatoid arthritis therapy.

Citing Articles

Preliminary Exploration of the Protective Mechanism of Eugenol Against Acute Liver Injury Induced by Thioacetamide Based on Metabolomics.

Chen H, Li M, Yan H, Yan J, Wang G, Gao L Molecules. 2024; 29(22).

PMID: 39598677 PMC: 11596261. DOI: 10.3390/molecules29225288.

Preventative and therapeutic potential of tocotrienols on musculoskeletal diseases in ageing.

Saud Gany S, Chin K, Tan J, Aminuddin A, Makpol S Front Pharmacol. 2023; 14:1290721.

PMID: 38146461 PMC: 10749321. DOI: 10.3389/fphar.2023.1290721.

Serum Metabolomic Alteration in Rats with Osteoarthritis Treated with Palm Tocotrienol-Rich Fraction Alone or in Combination with Glucosamine Sulphate.

Ekeuku S, Tan J, Al-Saadi H, Ahmad F, Elvy Suhana M, Arlamsyah A Life (Basel). 2023; 13(12).

PMID: 38137944 PMC: 10744932. DOI: 10.3390/life13122343.

Strategies to Enhance the Solubility and Bioavailability of Tocotrienols Using Self-Emulsifying Drug Delivery System.

Mohamad N Pharmaceuticals (Basel). 2023; 16(10).

PMID: 37895874 PMC: 10610013. DOI: 10.3390/ph16101403.

The Role of Tocotrienol in Arthritis Management-A Scoping Review of Literature.

Tejpal Singh H, Aminuddin A, Pang K, Ekeuku S, Chin K Pharmaceuticals (Basel). 2023; 16(3).

PMID: 36986484 PMC: 10052945. DOI: 10.3390/ph16030385.

References

Matsunaga T, Shoji A, Gu N, Joo E, Li S, Adachi T . γ-Tocotrienol attenuates TNF-α-induced changes in secretion and gene expression of MCP-1, IL-6 and adiponectin in 3T3-L1 adipocytes. Mol Med Rep. 2012; 5(4):905-9. PMC: 3493080. DOI: 10.3892/mmr.2012.770. View

Taysi S, Polat F, Gul M, Sari R, Bakan E . Lipid peroxidation, some extracellular antioxidants, and antioxidant enzymes in serum of patients with rheumatoid arthritis. Rheumatol Int. 2002; 21(5):200-4. DOI: 10.1007/s00296-001-0163-x. View

McInnes I, Schett G . Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol. 2007; 7(6):429-42. DOI: 10.1038/nri2094. View

Brigelius-Flohe R, Traber M . Vitamin E: function and metabolism. FASEB J. 1999; 13(10):1145-55. View

Lee K, Chen Y, Judson J, Chakravarthi S, Sim Y, Er H . The effect of water extracts of Euphorbia hirta on cartilage degeneration in arthritic rats. Malays J Pathol. 2009; 30(2):95-102. View

Feldmann M, Brennan F, Foxwell B, Maini R . The role of TNF alpha and IL-1 in rheumatoid arthritis. Curr Dir Autoimmun. 2002; 3:188-99. DOI: 10.1159/000060522. View

Herman S, Kronke G, Schett G . Molecular mechanisms of inflammatory bone damage: emerging targets for therapy. Trends Mol Med. 2008; 14(6):245-53. DOI: 10.1016/j.molmed.2008.04.001. View

Asquith D, Miller A, McInnes I, Liew F . Animal models of rheumatoid arthritis. Eur J Immunol. 2009; 39(8):2040-4. DOI: 10.1002/eji.200939578. View

Kasama T, Kobayashi K, Sekine F, Negishi M, Ide H, Takahashi T . Follow-up study of lipid peroxides, superoxide dismutase and glutathione peroxidase in the synovial membrane, serum and liver of young and old mice with collagen-induced arthritis. Life Sci. 1988; 43(23):1887-96. DOI: 10.1016/s0024-3205(88)80006-7. View

10.

Kamat J, Devasagayam T . Tocotrienols from palm oil as potent inhibitors of lipid peroxidation and protein oxidation in rat brain mitochondria. Neurosci Lett. 1995; 195(3):179-82. DOI: 10.1016/0304-3940(95)11812-b. View

11.

Navarro-Cano G, del Rincon I, Pogosian S, Roldan J, Escalante A . Association of mortality with disease severity in rheumatoid arthritis, independent of comorbidity. Arthritis Rheum. 2003; 48(9):2425-33. DOI: 10.1002/art.11127. View

12.

Goldring S . Pathogenesis of bone erosions in rheumatoid arthritis. Curr Opin Rheumatol. 2002; 14(4):406-10. DOI: 10.1097/00002281-200207000-00013. View

13.

Guo Y, Chen J, Xiong X, Wu D, Zhu H, Liang Q . Effect of Bizhongxiao decoction and its dismantled formulae on IL-1 and TNF levels in collagen-induced arthritis in rat synovial joints. Theor Biol Med Model. 2012; 9:47. PMC: 3507724. DOI: 10.1186/1742-4682-9-47. View

14.

Okazaki Y, Sawada T, Nagatani K, Komagata Y, Inoue T, Muto S . Effect of nuclear factor-kappaB inhibition on rheumatoid fibroblast-like synoviocytes and collagen induced arthritis. J Rheumatol. 2005; 32(8):1440-7. View

15.

Jones N, Pegues M, McCrory M, Kerr S, Jiang H, Sellati R . Collagen-induced arthritis is exacerbated in C-reactive protein-deficient mice. Arthritis Rheum. 2011; 63(9):2641-50. PMC: 3168703. DOI: 10.1002/art.30444. View

16.

Sokol R . Vitamin E and neurologic function in man. Free Radic Biol Med. 1989; 6(2):189-207. DOI: 10.1016/0891-5849(89)90117-2. View

17.

Hosomi A, Arita M, Sato Y, Kiyose C, Ueda T, Igarashi O . Affinity for alpha-tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs. FEBS Lett. 1997; 409(1):105-8. DOI: 10.1016/s0014-5793(97)00499-7. View

18.

Madhok R, Crilly A, Watson J, Capell H . Serum interleukin 6 levels in rheumatoid arthritis: correlations with clinical and laboratory indices of disease activity. Ann Rheum Dis. 1993; 52(3):232-4. PMC: 1005024. DOI: 10.1136/ard.52.3.232. View

19.

Soliman M, Ashcroft D, Watson K, Lunt M, Symmons D, Hyrich K . Impact of concomitant use of DMARDs on the persistence with anti-TNF therapies in patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register. Ann Rheum Dis. 2011; 70(4):583-9. PMC: 3048625. DOI: 10.1136/ard.2010.139774. View

20.

Lee D, Weinblatt M . Rheumatoid arthritis. Lancet. 2001; 358(9285):903-11. DOI: 10.1016/S0140-6736(01)06075-5. View