Affiliation:
1. Laboratory of Immunopharmacology and Experimental Therapeutics, Division of Cancer Research, Regional Cancer Centre, Medical College Campus, Thiruvananthapuram 695011, Kerala, India
2. Division of Crop Improvement, ICAR-Central Plantation Crops
Research Institute, Kasaragod 671124, Kerala, India
Abstract
Background:
Although Methotrexate (MTX) possesses a wide clinical spectrum of activity, its toxic
side effects on normal cells and drug resistance often hamper its successful outcome. Naringenin (NG) is one of
the promising bioactive flavonoids that are extensively found in grapes, citrus fruits, and fruit arils of Pithecellobium
dulce.
Objective:
Only a few experimental in vivo studies on the efficacy of NG against chemotherapeutic drugs have
been carried out. Aiming to fill this gap, the present study was carried out to characterize and identify its possible
therapeutic targets and also to explore its protective efficacy against MTX-induced tissue damage.
Methods:
Oxidative stress was induced in mice with MTX (20 mg/kg B.wt), and animals were orally administered
with 10 mg/kg B.wt NG for 10 consecutive days. On day 11, all animals were sacrificed, and hematological
and serum biochemical parameters were analyzed. The anti-oxidant efficacy of NG against MTX was evaluated
by quantifying tissue superoxide dismutase (SOD), glutatione peroxidase (GPx), reduced glutathione
(GSH) and catalase along with oxidative stress markers [malondialdehyde (MDA) and nitric oxide (NO)]. Further,
the histopathological analysis was performed to confirm the protective efficacy of FPD. In silico docking
studies were also performed to exploring anti-oxidant enzyme-based targets.
Results:
Our results showed that concurrent administration of NG counteracted oxidative stress induced by
MTX, as evidenced by increased expression of anti-oxidant markers, decreased expression of renal and hepatotoxicity
serum marker enzymes (p <0.05). A molecular docking study was performed using Auto dock vina to
understand the mechanism of ligand binding (S-NG and R-NG)with anti-oxidant enzymes. The binding affinity
of S-NG with catalase, GPx, ALP, and SGPT was -10.1, -7.1, -7.1, and -7.3 kcal/mol, respectively, whereas for
R-NG was -10.8, -7.1, -7.6, and -7.4 kcal/mol, respectively. Further, histopathological analysis affirmed the protective
efficacy of NG against MTX-induced hepatic and renal toxicities.
Conclusion:
Treatment with NG significantly reduced MTX-induced pancytopenia, renal, and hepatic toxicity.
Funder
University Grants Commission, India
Council of Scientific and Industrial Research, India
Publisher
Bentham Science Publishers Ltd.
Subject
Cancer Research,Pharmacology,Molecular Medicine
Cited by
4 articles.
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