Protective Effect of Curcumin and Cerium Oxide Nanoparticles on Carboplatin Induced Myelotoxicity and Hepatotoxicity in Adult Male Wistar Rats

Document Type : Original Article

Authors

1 Forensic Medicine and Clinical Toxicology, Faculty of Medicine , Zagazig University

2 Forensic medicine and toxicology department Faculty of medicine Zagazig university

3 Pathology Department, Faculty of medicine, Zagazig University

4 Human anatomy and embryology, faculty of medicine, Zagazig university

5 Clinical pharmacy department, faculty of medicine, Zagazig university

6 Clinical pharmacology Department, Faculty of medicine, Zagazig University

Abstract

Background: Carboplatin is a chemotherapeutic agent used in many types of cancers. Carboplatin adversely affects multiple organs like the bone marrow, liver, gastrointestinal tract, and kidney. Aim of the study: The aim of this work is to evaluate the potential protective role of curcumin and cerium oxide nanoparticles (CONPs) on carboplatin induced myelotoxicity and hepatotoxicity. Methods: Forty-eight adult male Wistar rats were classified into seven groups; I. Control (Subdivided into negative and positive control groups), II. Curcumin-treated, III. CONPs-treated, IV. Carboplatin intoxicated, V. Curcumin-treated carboplatin intoxicated, VI. CONPs-treated carboplatin intoxicated & VII. Curcumin & CONPs-treated carboplatin intoxicated groups.  Curcumin was administered orally, once daily for 4 consecutive weeks. CONPs, suspended in saline, and carboplatin were administered intraperitoneally once a week for 4 consecutive weeks.After 4 weeks, blood samples were collected after anesthesia of rats. The animals were then sacrificed, with bone marrow samples & livers collected for biochemical, histopathological and immunohistochemical studies. Results: Carboplatin treatment decreased blood cells count and elevated liver enzymes and bone marrow & hepatic malondialdehyde (MDA). It decreased GSH levels and causes DNA damage. Carboplatin induced hypocellularity in bone marrow samples and showed Strong 8-OHdG immunoreactivity. It also induced septal fibrosis with architectural distortion in liver tissue. Administration of either curcumin or CONPs ameliorated these toxic effects of carboplatin. Meanwhile the concurrent administration of curcumin and CONPs revealed much better improvement than each of them used alone. Conclusions: Combined administration of curcumin and CONPs ameliorated carboplatin-induced myelotoxicity and hepatotoxicity through antioxidant mechanism.

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