Cadmium induced pathophysiology: Prophylactic role of edible jute (Corchorus olitorius) leaves with special emphasis on oxidative stress and mitochondrial involvement

doi:10.1016/j.fct.2013.07.043

Food and Chemical Toxicology

Volume 60, October 2013, Pages 188-198

https://doi.org/10.1016/j.fct.2013.07.043 Get rights and content

Highlights

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Cd is a ubiquitous environmental pollutant.
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Oxidative stress has been proposed as a possible mechanism involved in Cd toxicity.
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Jute leaf is edible and contains significant quantity of phyto-antioxidants.
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This is the first report on protective role of jute leaf against Cd-intoxication.
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It mainly acts through reducing oxidative stress associated with Cd-intoxication.

Abstract

The present study was undertaken to evaluate the protective effect of aqueous extract of Corchorus olitorius leaves (AECO) against CdCl₂ intoxication. In vitro bioassay on isolated mice hepatocytes confirmed dose dependent cytoprotective effect of AECO. The CdCl₂ (30 μM) exhibited a significantly increased levels of lipid peroxidation, protein carbonylation along with the reduction of antioxidant enzymes and reduced glutathione levels in hepatocytes. AECO (200 and 400 μg/ml) + CdCl₂ (30 μM) 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-κB, caspase 3 and caspase 9. In in vivo assay, CdCl₂ (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 haematological parameters were significantly altered in the CdCl₂ 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.

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 absorption from the alimentary tract, Cd forms durable combinations with the apoprotein thionein, forming metallothionein, the holoprotein 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 unclear but Cd related augmented oxidative stress may be one of the critical features of Cd induced toxicity of critical tissues. Cd itself 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 activation of caspases and consequently cell death by apoptosis. In addition, it is also known that Bcl-2 family proteins are upstream regulator of mitochondrial events and play critical roles in mitochondrial-mediated cell death. Cd-intoxication up-regulates pro-apoptotic Bad and down-regulates anti-apoptotic Bcl-2 proteins regulated by NF-κB (Pal et al., 2011). So, it is clear that oxidative stress related responses versus signalling scenario are affected during Cd toxicity. Considering the relationship between Cd exposure and oxidative stress, attention has been focused on compounds having antioxidant properties to combat against Cd-induced toxicity.

Tossa jute, Corchorus olitorius Linn. (Family: Malvaceae) is a commercially important fibre crop with a production in excess of 2 million tons annually. Jute fibre is 100% bio-degradable and thus environmentally friendly. Jute fibre has high tensile strength, low extensibility, and ensures better breathability of fabrics. It is extensively used as packaging material for the variety of substances. Therefore, it occupies the second to cotton in economic importance (Maiti and Chakravarty, 1977). Jute plants produce edible leaves that are used as a vegetable and food ingredient common to the people of Eastern Asia and Africa (Zeid, 2002). Tossa jute has been used in folk medicine against different ailments including inflammation, dysentery, gastroenteritis, diabetes and tumors (Yan et al., 2013). Besides this jute leaves possess significant antioxidant activity (Oboh et al., 2009) due to presence of significant quantity of polyphenolics, ascorbic acid and α-tocopherol (Azuma et al., 1999). Polyphenolics enriched jute leaves have been reported to regulate the obesity in mice fed with high-fat diets through reduction of oxidative stress and enhancing β-oxidantion (Wang et al., 2011). Earlier studies by our group revealed that C. Olitorius leaves possess significant protective role against augmented oxidative stress associated with arsenic and lead intoxication (Dewanjee et al., 2013, Das J et al., 2011). The present study was undertaken to determine the protective role of C. olitorius leaves in Cd intoxication through in vitro and in vivo preclinical bioassays. The cytoprotective role of jute leaf was evaluated in isolated mouse hepatocytes. Intracellular antioxidant markers viz. antioxidant enzymes, reduced glutathione, lipid peroxidation and protein carbonylation were estimated in vitro. In addition, mechanistic aspect of Cd toxicity in hepatocytes and its protection by jute leaf extract was evaluated by immunoblotting. Finally the effect of Cd-intoxication in critical organs was estimated by suitable in vivo model in Wistar rats. Haematological, biochemical, antioxidant and histopathological markers were estimated to observe protective role of jute leaf against Cd toxicity.

Section snippets

Chemicals

Ammonium sulphate, 1-chloro-2,4-dinitrobenzene, 2,4-dinitrophenylhydrazine, 5,5-dithiobis(2-nitrobenzoic acid), ethylene diamine tetraacetic acid, N-ethylmaleimide, reduced nicotinamide adenine dinucleotide, nitro blue tetrazolium, phenazine methosulphate, potassium dihydrogen phosphate, reduced glutathione, sodium azide, sodium pyrophosphate, trichloro acetic acid, thiobarbituric acid and 5-thio-2-nitrobenzoic acid were purchased from Sisco Research Laboratory, Mumbai, India. Cadmium chloride

Dose and time dependent effect of AECO against CdCl₂ induced cellular damage

Results of the dose and time dependent protective effect of AECO in CdCl₂ induced cellular damage in isolated mouse hepatocytes was shown in Fig. 1. CdCl₂ (30 μM) exposure caused time dependent reduction (p < 0.01, compared with control hepatocytes) in cell viability up to 3 h. Simultaneous treatment of hepatocytes with AECO at different concentrations viz. 50, 100, 200 and 400 μg/ml with Cd (30 μM) prevented the reduction in cell death for 3 h in a concentration dependent manner. However, AECO at the

Discussion

The present study describes the protective role of aqueous extract of C. olitorius leaves in overall CdCl₂ intoxication with the help of suitable in vitro and in vivo models. It has been observed that CdCl₂ administration caused a significant oxidative stress and death in hepatocytes. Simultaneous treatment of the hepatocytes with AECO prevented Cd induced cellular toxicity. Oxidative free radicals are known to play a major role in Cd induced cellular damage in a variety of pathophysiological

Conflict of Interest

The authors declare that there is no conflict of interest.

Acknowledgements

Authors are thankful to University Grants Commission, New Delhi, India for providing financial support. Authors are also grateful to Jadavpur University, Kolkata, India and Ramakrishna Mission Vivekananda University, Narendrapur, India for providing necessary facilities for this study. The authors would like to thank the reviewers for their time and valuable comments.

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Citation Excerpt :
The healthy male SD rats were randomly divided into 5 groups (n = 6/group): Group I (control), Group II (CdCl2, 6.5 mg/kg body weight), Group III (Na2SeO3, 0.1 mg/kg body weight), Group IV (SPP, 100 mg/kg body weight) and Group V (Se-SPP, 100 mg/kg body weight). Rats from Group II to Group V were orally treated with CdCl2 (6.5 mg/kg body weight) for one day, then rats from Group III-Group V were respectively treated with tested drugs mentioned above for the next 2 days, Group I were treated with equivalent distilled water [10,43]. The rats were anesthetized by injecting with pentobarbital sodium (40 mg/kg) intraperitoneally 24 h after the final treatment.
Herein, selenium-containing polysaccharide from Spirulina platensis (Se-SPP) was prepared and its structural characteristics and protective role against Cd-induced toxicity in vivo and in vitro were investigated. Se-SPP was alkali-extracted from selenium-containing Spirulina platensis which was cultured in Zarrouk medium supplemented with Na₂SeO₃. The contents of carbohydrate, protein, uronic acid, sulfate and elements (including Se, C, H, O, N, and S) as well as the monosaccharide composition, molecular weight, surface morphology and FT-IR spectra of Se-SPP was compared to that of selenium-free polysaccharide (SPP). The results revealed that SPP and Se-SPP were both high-molecular-weight heteropolysaccharide with similar molecular weight and monosaccharide composition but significantly different selenium content, indicating that the covalently-bonding of a small amount of selenium did not destroy the original structure of polysaccharide. Furthermore, CdCl₂ was utilized to build Cd-intoxicated cells model in vitro and rats model in vivo respectively. Then, the protective effect of Se-SPP against cadmium-induced toxicity was assessed. The results demonstrated that Se-SPP treatment provided significant protection against Cd-induced toxicity, which was superior compared to that of SPP or Na₂SeO₃ alone. The enhancement of protective role may be affected by the covalently-bonding of selenium to polysaccharide.

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Cadmium induced pathophysiology: Prophylactic role of edible jute (Corchorus olitorius) leaves with special emphasis on oxidative stress and mitochondrial involvement

Highlights

Abstract

Introduction

Section snippets

Chemicals

Dose and time dependent effect of AECO against CdCl2 induced cellular damage

Discussion

Conflict of Interest

Acknowledgements

Int. J. Hyg. Environ. Health

Arch. Biochem. Biophys.

Toxicology

Free Radic. Biol. Med.

Food Chem.

Biochem. Pharmacol.

Food Chem. Toxicol.

Food Chem Toxicol.

Toxicol. In Vitro

Eur. J. Cell Biol.

Food Chem.

Food Chem.

J. Nutr. Biochem.

Int. J. Hyg. Environ. Health

Biochem. Biophys. Res. Commun.

Chem.-Biol. Interact.

Int. J. Hyg. Environ. Health

Toxicology

Arch. Biochem. Biophys.

Food Chem.

Food Chem.

Toxicology

Food Chem.

J. Trace Elem. Med. Biol.

J. Biol. Chem.

Food Chem.

Dose and time dependent effect of AECO against CdCl₂ induced cellular damage