Affiliation:
1. Cairo University
2. Theodor Bilharz Research Institute
3. Cairo University Faculty of Veterinary Medicine
4. National Research Centre
Abstract
Abstract
Doxorubicin (DOX) is an effective antitumor therapy but its use is limited by its deleterious toxic effects including nephrotoxicity and cardiotoxicity. The aim of this work was to assess the potential protective effect of Ceratonia siliqua methanol extract (CME) on DOX-induced nephrotoxicity in 5 groups of rats. Rats in groups 1and 2 were given normal saline while groups 3–5 were given Vitamin C (reference antioxidant, 250mg/kg), CME (500mg/kg) and CME (1000 mg/kg) for 5 days. On the 5th day, 1 hour after the last treatment dose, rats of groups 2–5 were given DOX in a dose of 15 mg/kg IP. DOX increased serum creatinine, urea, sodium and potassium and decreased GSH concentration, GST, CAT, SOD and MPO activities but increased MDA. It increased the inflammatory mediators (COX-2, IL-6, TNF-α, and NF-κβ) but decreased the anti-inflammatory cytokine (IL-10) and the Transforming growth factor-β (TGF-β). DOX has up-regulated COX-2, Caspase-3, Caspase-9, Bax and NF- κβ transcripts and down-regulated the anti-apoptotic Bcl-2 as assessed by immunohistochemistry and gene expression analysis. CME significantly improved the levels of kidney function parameters and restored the levels of the oxidative stress markers. It also decreased the level of COX-2, IL-6, TNF-α, and NF-κβ and stimulated the production of IL-10 and TGF-β. CME down-regulated the expression levels of the Bax, Cox-2 and caspases and up-regulated the anti-apoptotic Bcl-2. Microscopically, CME alleviated the DOX-induced renal damage in dose dependent manner. Phytochemical analysis revealed the presence of 26 compounds among which 4 major compounds (over 5%) in the CME. Acute toxicity test revealed that CME is not toxic up to 5 g/kg orally into rats. In conclusion, CME could effectively alleviate the deleterious effects of DOX on the kidney. The safety of carob extract encourages its use in the preparation of valuable therapeutic agents.
Publisher
Research Square Platform LLC
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