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Current Molecular Pharmacology

Author(s): Saeed Baharmi, Heibatullah Kalantari, Mojtaba Kalantar, Mehdi Goudarzi, Esrafil Mansouri and Hadi Kalantar*

DOI: 10.2174/1874467214666210531162741

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Pretreatment with Gallic Acid Mitigates Cyclophosphamide Induced Inflammation and Oxidative Stress in Mice

Article ID: e310521193731 Pages: 9

  • * (Excluding Mailing and Handling)

Abstract

Background: Cyclophosphamide (CP) as an alkylating compound has been widely applied to treat cancer and autoimmune diseases. CP is observed to be nephrotoxic in humans and animals because it produces reactive oxygen species. Gallic Acid (GA), a polyhydroxy phenolic compound, is reported to exhibit antioxidant and anti-inflammatory effects.

Objective: The current research aimed at evaluating the GA effect on CP-related renal toxicity.

Methods: In total, 35 male mice were assigned to 5 groups. Group1: receiving normal saline, group 2: CP group, receiving one CP injection (200 mg/kg; i.p.) on day 6. Groups 3 and 4: GA+CP, GA (10 and 30 mg/kg; p.o.; respectively) received through six consecutive days plus CP on the 6th day 2 hr after the last dose of GA, group 5: received GA (30 mg/kg; p.o.) for six consecutive days. Then on day 7, blood samples were collected for determining Creatinine (Cr), serum kidney injury molecule-1 (KIM-1), Blood Urea Nitrogen (BUN), and Neutrophil Gelatinase-Associated Lipocalin (NGAL) concentrations. Malondialdehyde (MDA), Nitric Oxide (NO) concentration, Catalase (CAT), Superoxide Dismutase (SOD), Glutathione (GSH), Glutathione Peroxidase (GPx) activities, and IL-1β, TNF-α levels were assessed in renal tissue.

Results: CP administration significantly increases KIM-1, NGAL, Cr, BUN, MDA, NO, IL-1β, and TNF-α level. It also decreases GSH concentration, SOD, GPx, and CAT function. Pretreatment with GA prevented these changes. Histopathological assessments approved the GA protective effect.

Conclusion: Our results showed that GA is possibly effective as a protective agent in cyclophosphamide- associated toxicities.

Keywords: Cyclophosphamide, inflammation, oxidative stress, nephrotoxicity, gallic acid, mice

Graphical Abstract

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