Indian Journal of Experimental Biology Vol. 53, May 2015, pp. 281-291 Protective effect of Clerodendrum colebrookianum leaves against iron-induced oxidative stress and hepatotoxicity in Swiss albino mice Abhishek Das 1 , Dipankar Chaudhuri 2 , Nikhil Baban Ghate 2 , Sourav Panja 2 , Anupam Chatterjee 1 & Nripendranath Mandal 2 * 1 Department of Biotechnology & Bioinformatics, North-Eastern Hill University, Shillong- 793 022, Meghalaya, India 2 Division of Molecular Medicine, Bose Institute, Kolkata- 700 054, West Bengal, India Received 01 May 2014; revised 11 June 2014 Liver toxicity due to iron overload leads to oxidative damage of proteins, lipids and nucleic acids which in turn manifests several human diseases. Here, we evaluated the improving effect of Clerodendrum colebrookianum leaf on iron overload induced liver injury along with in vitro iron chelation and the protection of Fenton reaction induced DNA damage was conducted. Iron overload was induced by intraperitoneal administration of iron-dextran into mice. Post oral administration of different doses of the extract (50, 100 and 200 mg/kg body weight) showed significant decrease in different biochemical markers such as liver iron, serum ferritin and serum enzyme levels, along with decreased lipid peroxidation, protein oxidation and collagen content. In addition, the extract effectively enhanced the antioxidant enzyme levels and also exhibited the potential activity of the reductive release of ferritin iron. The protective effect of C. colebrookianum extract on injured liver was furthermore supported by the histopathological studies that showed improvement histologically. In conclusion, the present results demonstrated the hepatoprotective efficiency of C. colebrookianum leaf in iron overloaded mice, and hence, a potential iron chelating drug for iron overload diseases. Keywords: Antioxidant enzymes, East Indian Glory Bower, Folk medicine, Ferritin, Hypertension, Iron overload, Lipid peroxidation, Protein carbonyl, Traditional medicine Being an imperative trace element of the body for its growth and survival, iron exists in hemoglobin, myoglobin, cytochromes, iron-dependent metalloenzymes and enzymes with iron sulfur complexes 1 . Although an optimum level of iron is always maintained by the cells to balance between essentiality and toxicity, in some situations the balance is disrupted, resulting in iron overloaded toxicity. Generation of highly reactive HO • by virtue of Fenton’s reaction causes immense injury to various biomolecules leading to oxidative stress 2 , resulting in inflammatory responses in hepatic cells. The first line of defense against oxidative injury, the intrinsic antioxidant system involving superoxide dismutase (SOD), catalase (CAT) and glutathione-s-transferase (GST) enzymes and reduced glutathione (GSH), starts behaving abnormally as their levels hugely deviate from their respective normal conditions. The major mechanism of iron-induced hepatotoxicity appears due to increased hepatic lipid peroxidation (LPO) 3 and single and double-strand breaks in DNA 4 , which have been implicated in the pathophysiology of iron overload diseases including hemochromatosis, L-thalassemia, ischemic heart disease and cancer 5,6 . Fatty ballooning degeneration is one of the major detriments resulting from oxidative damage to lipids of hepatic parenchyma. Damage to hepatocellular proteins causes factors like collagen and protein carbonyl contents to strongly deviate from their normal course. This leads to serious pathological conditions like loss of overall tissue integrity, periportal vein inflammation and hepatocellular necrosis which is followed by the migration of fibrosis inside the deformed periportal vein; the same being a hallmark of hepatic damage. Hepatic damage also induces leakage of cellular enzymes into the bloodstream, resulting in elevated levels of serum ALAT, ASAT, ALP and bilirubin 1 Since total iron content in liver increases, ferritin, a storage protein, is incapable of hoarding iron and thus spills it in its Fe 3+ form in the blood. Analyzing the reductive release of ferritin becomes another hallmark for estimating the extent of damage due to excess iron. In order to bridge the gap between calculated assumptions and —————— *Correspondence Phone: +91-33-2569-3285, Fax: +91-33-2355-3886 E-mail: mandaln@rediffmail.com