Ceratonia siliqua pods (Carob) methanol extract alleviates doxorubicin-induced nephrotoxicity via antioxidant, anti-inflammatory and anti-apoptotic pathways in rats

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Atta A.H.; Atta S.A.; Khattab M.S.; Abd El-Aziz T.H.; Mouneir S.M.; Ibrahim M.A.; Nasr S.M.; Emam S.R.

Journal: Environmental Science and Pollution Research

Publisher: Springer

Publication Date: 21 June 2023

Volume / Issue: Volume 30 / Issue 35

Pages: 83421–83438

ISSN: 9441344

DOI: 10.1007/s11356-023-28146-z

Scopus: View on Scopus

PubMed: 37341944

Document Type: Article

Access: All Open Access; Green Open Access; Hybrid Gold Open Access

Authors and Affiliations

Atta A.H., Pharmacology Department, Faculty of Veterinary Medicine, Cairo University, Giza, 1211, Egypt; Atta S.A., Immunology Department, Theodor Belharz Research Institute, Giza, 12411, Egypt; Khattab M.S., Pathology Department, Faculty of Veterinary Medicine, Cairo University, Giza, 1211, Egypt; Abd El-Aziz T.H., Department of Parasitology and Animal Diseases, National Research Centre, 33 Bohouth St, Dokki, Giza, 12622, Egypt; Mouneir S.M., Pharmacology Department, Faculty of Veterinary Medicine, Cairo University, Giza, 1211, Egypt; Ibrahim M.A., Biochemistry and Molecular Biology Department, Faculty of Veterinary Medicine, Cairo University, Giza, 1211, Egypt; Nasr S.M., Department of Parasitology and Animal Diseases, National Research Centre, 33 Bohouth St, Dokki, Giza, 12622, Egypt; Emam S.R., Pharmacology Department, Faculty of Veterinary Medicine, Cairo University, Giza, 1211, Egypt

Abstract

Doxorubicin (DOX) is an anti-neoplastic therapy, but its use is limited by its deleterious toxic effects including nephrotoxicity and cardiotoxicity. This work aimed at assessing the potential protective effect of Ceratonia siliqua methanol extract (CME) on DOX-induced nephrotoxicity in 5 groups of Wistar rats. Nephrotoxicity was induced experimentally by intraperitoneal (IP) injection of DOX (15 mg/kg). DOX increased serum creatinine, urea, sodium, and potassium levels. It elevated MDA levels in the renal tissue but decreased the concentration of GSH and the activity of GST, CAT, and SOD. Meanwhile, it decreased the level of immunomodulatory anti-inflammatory mediators: IL-10 and TGF-β, as well as the activity of MPO but increased the level of IL-6, TNF-α, and caspase-3 in the renal tissue. DOX has upregulated COX-2, caspase-9, and Bax gene expression and downregulated the Bcl-2 gene expression. Immunolabeling of renal tubular epithelium in DOX-intoxicated rats was moderate to strong against Bax, COX-2, and NF-kβ and weak against Bcl-2. Treatment with CME significantly restored the levels of kidney function parameters and the levels of oxidative stress markers. It stimulated the production of IL-10 and TGF-β and decreased the level of IL-6 and TNF-α. CME reverted the gene expression of COX-2, caspase-9, and Bax. Microscopically, CME alleviated the DOX-induced renal damage. Phytochemical analysis revealed the presence of 26 compounds in the CME. No signs of acute toxicity were recorded by CME up to 4000 mg/kg b. wt. orally into mice. Finally, 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. © The Author(s) 2023.

Keywords

Anti-apoptotic; Anti-Inflammatory; Antioxidant; Carob; Ceratonia siliqua; Doxorubicin; Nephrotoxicity; Phytochemistry; Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; bcl-2-Associated X Protein; Caspase 9; Cyclooxygenase 2; Fabaceae; Interleukin-10; Interleukin-6; Kidney; Methanol; Mice; Oxidative Stress; Rats; Rats, Wistar; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha; Gene expression; Industrial poisons; Metabolism; Tissue; Urea; algaroba; antiinflammatory agent; interleukin 10; interleukin 6; protein Bax; tumor necrosis factor; Anti-inflammatories; Apoptotic; Genes expression; Methanol extract; Renal tissue; animal; mouse; rat; Wistar rat

Citation Information

Scopus Citations: 37

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