International Journal of Biology Research 44 International Journal of Biology Research ISSN: 2455-6548; Impact Factor: RJIF 5.22 Received: 09-08-2019; Accepted: 11-09-2019 www.biologyjournal.in Volume 4; Issue 4; October 2019; Page No. 44-50 Effect of Punica granatum seeds on Doxorubicin and Gamma Radiation -Induced Hepatotoxicity in Wistar Rats Mohamed A Bashandy 1 , Diaa Farrag Ibrahim 2 , Hesham F Hasan 3 , Mahmoud A El-Sharkawy 4 1-2-4 Department of Zoology, Faculty of Science, Al-Azhar University, Cairo, Egypt 3 Radiation biology Department, National Center for Radiation Research and Technology, Atomic energy authority, Cairo, Egypt Abstract Punica granatum Linn popularly known as ‘Pomegranate’ is a rich source of flavonoids. Flavonoids have been implicated in Hepatoprotective activity. Objectives: To evaluate effect of Punica granatum seeds and its flavonoids on doxorubicin-induced hepatotoxicity in Wistar rats. Materials and Methods: The Anthocyanidins of Punica granatum (100 mg/kg) extracts as potent antioxidants in improving the toxicity of doxorubicin (DOX) and/or gamma radiation in albino Wistar rats. The rats were injected with DOX (2.5 mg/kg, i.p.) and/or exposed the rats to irradiation (2 Gy, whole body) weekly, for four consecutive weeks. The antioxidant treatments were used daily via oral gavages for two weeks protection period and during the experiment (4 weeks). The levels of aminotranferases (ASAT, ALAT), alkaline phosphatase (ALP) and Superoxide dismutase (SOD), Catalase (CAT), Glutathione reductase (GSH) and Lipid peroxidation (TBARS) levels in liver were measured. Result: In the present study, DOX and/or gamma radiation revealed increase in the hepatic biomarkers (ASAT, ALAT and ALP), also decreased in total protein and albumin, which were significantly decreased after pretreatment with Pomegranate (POM) (100 mg/kg), while decreased in total protein and albumin. DOX and/or gamma radiation significantly decreased levels of SOD, CAT, and GSH which were restored with POM. Conclusion: The study concludes that POM possess potential hepatoprotective activity which may be attributated to its flavonoids (anthocyanidins), having therapeutic potential in treatment of liver disorders. Keywords: Punica granatum, hepatotoxicity, doxorubicin and gamma radiation Introduction Doxorubicin (DOX) used for the treatment of cancer in 1969, this chemical has demonstrated high antitumor efficacy. However, its use in chemotherapy has been limited largely due to its diverse toxicities, including cardiac, renal, hematological and testicular toxicity (Gillick et al., 2002; [27] Yilmaz et al., 2006) [75] alterations of DNA and the production of free radicals (Quiles et al., 2002) [57] , mitochondrial damage and iron-dependent oxidative damage to biological macromolecules (Thomas et al., 1987). DOX is an anthracyclic antibiotic with broad spectrum of anti- neoplastic activity. Oxidative stress has been demonstrated in DOX mediated myocardial, renal (Fadillioglu et al., 2004) [23] and liver (Kwiecien et al., 2006) damages. DOX injection substantially increased the peroxidative damage in the myocardium, hepatic and renal tissues and markedly increased the serum Creatinine, BUN, ALAT and ASAT (Saad et al., 2001) [60] . DOX treatment also induced peroxidative alterations in various tissues (Chen et al., 1998; [16] Todorova et al., 2009) [69] , which was evident by significant elevation in SOD and CAT. Scientific and technological advancements have increased radiation burden in humans, since exposure to low level of radiation frequently has become common during medical diagnostic procedures, space or air travel cosmic radiation and use of certain electronic gadgets. Exposure to ionizing radiation can induce functional and structural changes in the liver (Kim & Jung, 2017) [39] , mainly caused by the excess of free radicals and oxidative stress. Oxidative stress is a crucial factor in liver damage (Cichoż-Lach & Michalak, 2014) [17] Hepatocyte's lipids, proteins, and nucleic acids are among the cellular structures to be affected primarily by reactive oxygen species (ROS). It is well documented that lipid peroxidation disrupts the normal membrane structure (Niki, 2009), proteins oxidation affect signal transduction and DNA repair enzymes (Dalle-Donne et al., 2003) [18] , and DNA oxidation leads to the formation of 8‐hydroxy‐deoxyguanosine (8‐OHdG) and mutation in the DNA strands (Voulgaridou et al., 2011) [71] . These processes result in structural and functional abnormalities in the liver (Cichoż-Lach & Michalak, 2014) [17] . The effects of ROS are counteracted by antioxidants including glutathione (GSH), the most important antioxidant molecule (Valko et al., 2007) [70] , superoxide dismutase, GSH peroxidase, and catalase (CAT). In addition to oxidative stress, alteration in the detoxification pathways can affect the integrity of the liver (Cederbaum, 2017) [15] . Detoxification inside the liver cells depends on phase 1 catalyzed by the cytochrome P450 (CYP450) enzyme group and the formation of free radicals, which are further metabolized by phase 2 involving conjugation reactions and the formation of a water‐soluble component, which can be excreted through urine or bile. The phase 2 enzyme systems include both Uridine 5′‐diphospho‐glucuronosyltransferase and GSH transferase (GSH‐T). Several studies have shown evidence of associations between induced phase 1 and/or decreased