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Reduction of oxidative stress by an ethanolic extract of leaves of Piper betle (Paan) Linn. decreased methotrexate-induced toxicity

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Abstract

Methotrexate (MTX), a folate antagonist, is currently used as first line therapy for autoimmune diseases like rheumatoid arthritis and psoriasis, but its use is limited by the associated hepatotoxicity. As leaves of Piper betle, belonging to family Piperaceae, have antioxidant and anti-inflammatory properties, the present study was undertaken to investigate the potential of Piper betle leaf extract (PB) in attenuating MTX-induced hepatotoxicity. Rats pre-treated with PB (50 or 100 mg kg−1 b.w., p.o.) were administered with a single dose of MTX (20 mg kg−1, b.w., i.p.) and its hepatoprotective efficacy was compared with folic acid (1 mg kg−1 b.w., i.p.), conventionally used to minimize MTX-induced toxicity. MTX-induced hepatotoxicity was confirmed by increased activities of marker enzymes, alanine transaminase, aspartate transaminase, and alkaline phosphatase which were remitted by pre-treatment with PB and corroborated with histopathology. Additionally, MTX-induced hepatic oxidative stress which included increased generation of reactive oxygen species, enhanced lipid peroxidation, depleted levels of glutathione and decreased activities of antioxidant enzymes was effectively mitigated by PB, indicative that its promising antioxidant-mediated hepatoprotective activity was worthy of future pharmacological consideration.

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Acknowledgments

The work received financial assistance from the Department of Biotechnology, Govt. of India (BT/PR4641/MED/30/742/2012).

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Authors and Affiliations

  1. Department of Pharmacology, Institute of Postgraduate Medical Education and Research, 244 B, Acharya JC Bose Road, Kolkata, West Bengal, 700020, India

    Soumita De & Mitali Chatterjee

  2. Department of Pharmaceutical Technology, Jadavpur University, 188, Raja Subodh Chandra Mullick Road, Jadavpur, Kolkata, West Bengal, 700032, India

    Soumita De & Tuhinadri Sen

  3. School of Natural Product Studies, Jadavpur University, 188, Raja Subodh Chandra Mullick Road, Jadavpur, Kolkata, West Bengal, 700032, India

    Soumita De & Tuhinadri Sen

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  1. Soumita De
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Correspondence to Mitali Chatterjee.

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All procedures performed in animals were in accordance with the ethical standards of Institute of Post Graduate Medical Education and Research, Kolkata, India (CPCSEA Registration No. 544/PO/c/02/CPCSEA), where the studies were conducted.

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The authors declare that we have no conflict of interest.

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De, S., Sen, T. & Chatterjee, M. Reduction of oxidative stress by an ethanolic extract of leaves of Piper betle (Paan) Linn. decreased methotrexate-induced toxicity. Mol Cell Biochem 409, 191–197 (2015). https://doi.org/10.1007/s11010-015-2524-x

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  • DOI: https://doi.org/10.1007/s11010-015-2524-x

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