An in vivo and in silico approach to elucidate the Tocotrienol-mediated fortification against infection and inflammation induced alterations in antioxidant defense system

M.S. Khan 1,2, M.K.A. Khan 2, M.H. Siddiqui 2, J.M. Arif 2,3

¹Department of Biochemistry, J N Medical College, A M University, Aligarh (India)

² Department of Biotechnology, Integral University, Lucknow (India)

³ Department of Biochemistry, University of Hail, Hail (Saudi Arabia)

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• Pharmacology

Background: Tocotrienol (Tocomin) are naturally occurring analogues of vitamin E family and has been reported to possess a potent free radical scavenging activity. In the present study we have initially investigated protective role of tocotrienol against infection and inflammation induced alterations in tissues antioxidant defense system, as well as speculated, via in silico docking studies, that tocotrienol can act by directly binding to antioxidant enzymes.

Materials and Methods: Syrian hamsters were injected with bacterial lipopolysaccharide (LPS, 200 µg), zymosan (20 mg), or turpentine (0.5 ml) to mimic acute infection, acute systemic inflammation, and acute localized inflammation, respectively, which are responsible for the generation of plenty of free radicals that causes oxidative stress. Tocomin (10 mg) was administered daily for 10 days before and 12 h after lipopolysaccharides (LPS) or 24 h after turpentine or zymosan injection. Molecular docking studies were performed using Autodock 4.0.

Results: Our results show a significant decrease in the activities of antiperoxidative enzymes, glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), glutathione-s-transferase (GST), as well as reduced glutathione (GSH), in liver and kidney of LPS, turpentine or zymosan stressed hamsters. Feeding of 10 mg Tocomin to stressed hamsters was quite effective in reversing/normalizing the altered levels of enzymatic and nonenzymatic antioxidants in liver and kidney. In order to explore the interaction between tocotrienol and antioxidant enzymes a molecular docking study was performed. The results showed good interaction in term of binding energy and inhibition constant in the following order GR >CAT > SOD >GST >GPx.

Conclusion: Our in vivo and in silico results for the first time indicate that tocotrienol significantly alleviate the condition of oxidative stress not only by its potent free radical scavenging properties but also may be by interacting directly and strongly with antioxidant enzymes as proved by molecular docking simulations.

Corresponding Author: Mohammad Salman Khan, Ph.D.; e-mail: contactskhan@gmail.com

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