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

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. Eldakroory et al . 2 Vol. XXI, No. 1, January 2013 Mansoura J. Forensic Med. Clin. Toxicol. reperfusion injury of the brain, heart and retina (Ashraf et al., 2010). Utilization of the leaves of this plant as an herbal medicine for treating a variety of diseases can be traced back to thousands of years in ancient China. The leaves of GinkgoBiloba containing ginkgo-flavone glycosides which can scavenge superoxide, hydroxyl radicals and nitric oxide (NO) and protect myocardia from ischemia reperfusion injury (Shen et al., 2011). Ferulic acid is a hydroxycinnamic acid, a type of organic compound. It is an abundant phenolic phyto-chemical found in plant cell wall components such as arabinoxylans as covalent side chains. It is found in seeds of plants such as rice, wheat, oats, as well as coffee, apple, artichoke, peanut, orange and pineapple. It can be extracted from wheat bran and maize bran using concentrated alkali. Like many phenols, it is an antioxidant in vitro in the sense that it is reactive toward free radicals, quenching lipid peroxidative chains (Fereidoon and Marian, 2004; Yogeeta et al., 2006; Barone et al., 2009). The aim of study is to evaluate the efficacy of Ferulic acid and Ginkgo Biloba in counteracting doxorubicin toxicity.