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Published on:March 2021
Indian Journal of Pharmaceutical Education and Research, 2021; 55(1s):s265-s274
Original Article | doi:10.5530/ijper.55.1s.59

Ethanolic Extract of Capparis decidua Fruit Ameliorates Methotrexate-Induced Hepatotoxicity by Activating Nrf2/HO-1 and PPARγ Mediated Pathways


Authors and affiliation (s):

Preetha Santhakumar1,*, Anitha Roy2, Karthik Ganesh Mohanraj3, Selvaraj Jayaraman4, Rajkumar Durairaj5

1Department of Physiology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, INDIA.

2Department of Pharmacology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, INDIA.

3Department of Anatomy, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, INDIA.

4Department of Biochemistry, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, INDIA.

5Department of Anatomy, National Institute for Empowerment of Persons with Multiple Disabilities, Muttukadu, Chennai, Tamil Nadu, INDIA.

Abstract:

Introduction: Methotrexate, a folate antimetabolite, immunosuppressant and cytotoxic chemotherapeutic agents employed for malignant conditions. Continuous exposure of methotrexate produces adverse side effects especially liver toxicity. Recently, medicinal plants are gaining an importance owing to their phytoconstituents which are responsible for their medicinal value. Capparis decidua is one such medicinal plant widely used in the traditional system of medicine. No study has focused the mechanism of hepatoprotective property of Capparis decidua via Nrf2/HO-1 and PPARγ signaling pathway. Hence the study was mainly focused on its ability to modulate Nrf2 and PPARγ signaling in the methotrexate induced hepatotoxicity in Wistar rats. Materials and Methods: 30 female Wistar albino rats were divided into five groups. Following a single dose of methotrexate (20 mg/kg, intraperitoneally) injection, Wistar rats were orally administered with Capparis decidua at a doses of 250 mg/kg and 500mg/kg for 14 days. AST, ALT and ALP, antioxidants like GST, GPx, GR, were assessed in hepatic tissue. LPO, H2O2, OH radicals were assessed. mRNA expression of Nrf2, HO-1, PPARү was carried using real-time PCR in hepatic tissue. Nrf2, TNF-α, IL -1β proteins were assessed using western blot. Results: Methotrexate administration significantly increased liver function marker, caused lipid peroxidation and decreased antioxidants levels. Treatment with Capparis decidua caused significant decrease in AST, ALT, ALP, levels and significant increase in GST, GPx, GR. Methotrexate decreased mRNA expression of Nrf2, HO-1, PPARγ. Capparis decidua prevented methotrexate induced liver injury by upregulating Nrf2 and PPARү signaling pathway. Capparis decidua also suppressed inflammatory markers like TNF-α and IL -1β proteins. Conclusion: Capparis decidua has thus attenuated methotrexate induced hepatotoxicity and this could be via up-regulation of Nrf2/HO-1 and PPARγ pathways.

Key words: Antioxidant, Capparis decidua, Hepatotoxicity, Methotrxate, Nrf2, PPARү.

 




 

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The Official Journal of Association of Pharmaceutical Teachers of India (APTI)
(Registered under Registration of Societies Act XXI of 1860 No. 122 of 1966-1967, Lucknow)

Indian Journal of Pharmaceutical Education and Research (IJPER) [ISSN-0019-5464] is the official journal of Association of Pharmaceutical Teachers of India (APTI) and is being published since 1967.

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