Evaluation of Doxorubicin Toxicity; Does Ferulic Acid have A Possible Protective Effect Like Ginkgo Biloba ?

Document Type : Original Article

Authors

1 Forensic Med. & Clin. Toxicology, Mansoura Faculty of Medicine,Egypt

2 Department of Pharmacology, Mansoura University, Egypt

3 Department of Physiology,Mansoura University , Egypt

4 Department of Pathology, Mansoura University, Egypt

Abstract

Doxorubicin (Dox) is an anthracycline antibiotic agent used in the treatment of solid and haematopoietic tumours, but its use is limited by its diverse toxicities. The objective of this study was to investigate the role of ferulic acid (FA), a natural antioxidant agent, and Ginkgo Biloba (GB) extract, a cytoprotective herb-derived agent, in protection against Doxorubicin-induced toxicity. Fourty albino rats weighing between 150 and 200gm were used in this study. Animals were equally divided into four groups; Group I (control group) was given 1ml/kg saline. Group II was given 2.5 mg/kg Dox intraperitoneal three times weekly for two weeks. Group III was given an GB orally in a dose of 100mg/kg/d one week before giving Dox then with Dox for two weeks; GB daily and intraperitoneal injection of 2.5mg/kg Dox three times weekly after GB by 1 hour. Group IV was given FA in a dose of 110 mg/kg/d orally for one week then with Dox for two weeks; FA daily and  intraperitoneal injection of 2.5mg/kg Dox three times  weekly after FA by 1 hour. Animals were sacrificed 48 hours following the last Dox dose by cervical dislocation. Intra cardial blood sample was taken for biochemical assays of serum creatinine, serum lactate dehydrogenase, creatine phosphokinase, AST and ALT were done. Half of kidneys, heart and liver were removed for the remaining half of tissues were used to estimate levels of MDA, GSH, SOD and histological analysis catalase. The results showed that MDA was increased in all tissues and serum in Dox group; while histopathological examination, SOD and catalase activities were decreased. Overall, there was evident significant improvement of  biochemical markers of Dox toxicity and decreasing the toxic histopathological effect of Dox  in both GB-treated and FA treated groups especially liver and heart in GB group and kidney in FA group. The results of this study could clarify the role of a natural ultimate solution (FA) in addition to the common popular herbal drug GB in prevention of serious Dox treatment toxicity.