Cadmium induced pathophysiology: Prophylactic role of edible jute (Corchorus olitorius) leaves with special emphasis on oxidative stress and mitochondrial involvement Saikat Dewanjee a,⇑ , Moumita Gangopadhyay a,b , Ranabir Sahu a , Sarmila Karmakar a a Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Raja S C Mullick Road, Kolkata 700 032, India b Division of Biophysics and Structural Genomics, Saha Institute of Nuclear Physics, Bidhannagar, Kolkata 700 064, India article info Article history: Received 22 May 2013 Accepted 16 July 2013 Available online 25 July 2013 Keywords: Antioxidant CdCl 2 Cadmium toxicity Corchorus olitorius Oxidative stress abstract The present study was undertaken to evaluate the protective effect of aqueous extract of Corchorus olito- rius leaves (AECO) against CdCl 2 intoxication. In vitro bioassay on isolated mice hepatocytes confirmed dose dependent cytoprotective effect of AECO. The CdCl 2 (30 lM) exhibited a significantly increased lev- els of lipid peroxidation, protein carbonylation along with the reduction of antioxidant enzymes and reduced glutathione levels in hepatocytes. AECO (200 and 400 lg/ml) + CdCl 2 (30 lM) could significantly restore the aforementioned oxidation parameters in hepatocytes. Beside this, AECO could significantly reduce Cd-induced increase in Bad/Bcl-2 ratio and the over-expression of NF-jB, caspase 3 and caspase 9. In in vivo assay, CdCl 2 (4 mg/kg body weight, for 6 days) treated rats exhibited a significantly increased intracellular Cd accumulation, oxidative stress and DNA fragmentation in the organs. In addition, the hae- matological parameters were significantly altered in the CdCl 2 treated rats. Simultaneous administration of AECO (50 and 100 mg/kg body weight), could significantly restore the biochemical, antioxidant and haematological parameters near to the normal status. Histological studies of the organs supported the protective role of jute leaves. Presence of substantial quantity of phenolic compounds and flavonoids in extract may be responsible for overall protective effect. Ó 2013 Elsevier Ltd. All rights reserved. 1. Introduction Cadmium (Cd) is a toxic metal emanating from both industrial and agricultural sources with biological half-life in the range of 10–30 years (Xiang et al., 2012). Human body may be exposed to Cd mainly through air, water or even through foods. After absorp- tion from the alimentary tract, Cd forms durable combinations with the apoprotein thionein, forming metallothionein, the holo- protein that plays an important role in further metabolism of this metal. In chronic exposure, Cd has been considered to be a multi- target toxicant, and it causes damage of vital organs namely liver, kidney, brain, pancreas, intestine and heart (Al-Saleh et al., 2008; Oymak et al., 2009; Mortensen et al., 2011; Kossowska et al., 2013). However, the mechanism of Cd toxicity remains fairly un- clear but Cd related augmented oxidative stress may be one of the critical features of Cd induced toxicity of critical tissues. Cd it- self is unable to generate free radicals directly, since it has only one oxidation state. However, indirect generation of various radicals involving the superoxide radical, hydroxyl radical and nitric oxide has been reported (Galan et al., 2001; Ghosh et al., 2010). It has been reported that Cd increases the free iron (Fe) concentration possibly by its replacement in various proteins and hence increases the cellular amount of free redox-active metals (Cuypers et al., 2010). Free redox-active metals directly enhance the generation of hydroxyl radicals through the Fenton reaction (Watanabe et al., 2003). Reduction of the oxidised metal ion can be achieved by the Haber-Weiss reaction (Karihtala and Soini, 2007) with superoxide radicals as a substrate, but also other reducing agents, such as ascorbate can catalyse this reaction (Winterbourn, 1979). Cd also exhibits other ways to induce oxidative stress. As a thiol- affectionate metal, Cd targets the highly abundant cellular GSH, thiol antioxidant (Nair et al., 2013). Thiol affinity of Cd is several times greater than its affinity for phosphate, chloride, carboxyl, or amino groups (Rikans and Yamano, 2000). Depletion of the GSH results impairment of the cellular redox balance leading to oxidative stress. Mitochondria are the primary cellular targets of Cd (Muller, 1986). Mitochondria are a major cellular site of electron-transfer-chain-dependent production of oxidative free radicals during Cd-intoxication. Later resulted decrease in mitochondrial membrane potential, which further leads to the 0278-6915/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.fct.2013.07.043 ⇑ Corresponding author. Address: Advanced Pharmacognosy Research Laboratory (3rd Floor), Department of Pharmaceutical Technology, Jadavpur University, Raja S C Mullick Road, Kolkata 700 032, India. Tel.: +91 33 24146666x2043; fax: +91 33 28371078. E-mail address: s.dewanjee@yahoo.com (S. Dewanjee). Food and Chemical Toxicology 60 (2013) 188–198 Contents lists available at ScienceDirect Food and Chemical Toxicology journal homepage: www.elsevier.com/locate/foodchemtox