Cadmium-induced induction of cell death in human lens epithelial cells: Implications to smoking associated cataractogenesis

Nilesh M. Kalariya, Bindu Nair, Denish K. Kalariya, Nancy K. Wills, Frederik J.G.M. van Kuijk

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Cadmium is reported to accumulate in human eye tissues suggesting its implication in diverse ocular pathology. Using an in vitro cell culture model we investigated the effects of cadmium on human lens epithelial cells (HLECs) (HLE-B3). We observed cadmium-induced dose- as well as time-dependent decline in HLECs viability which was exacerbated significantly upon reduction of intracellular glutathione levels by buthionine sulfoximine (BSO). There was a dose-dependent significant increase in lactate dehydrogenase (LDH) release from HLECs suggesting cadmium-induced alteration of membrane integrity as well as necrotic cell death. The decline in cell viability was also due to apoptosis of the HLECs as determined by quantifying % apoptotic cells as well as PARP cleavage. Moreover, release of apoptosis inducing factor (AIF) into the cytosol was also detected. Cadmium was also observed to increase oxidative stress, lipid peroxidation and activation of MAPK pathway in HLECs. Antioxidants like N-acetylcysteine (NAC) and α-Tocopherol significantly prevented cadmium-induced toxicity in HLECs. Our findings suggest that cadmium-induced elevated oxidative stress as well as activation of MAPK signaling cascade eventually led to cell death of HLECs through apoptosis as well as necrosis. The loss of HLECs by cadmium could possibly explain its implication in cataract development particularly associated with smoking.

Original languageEnglish (US)
Pages (from-to)56-62
Number of pages7
JournalToxicology Letters
Volume198
Issue number1
DOIs
StatePublished - Sep 2010

Bibliographical note

Funding Information:
This work was supported by Philip Morris USA Inc. and Philip Morris International (N.W.), Wilkins AMD Fund (F.vK.). Denish Kalariya received scholarship from Babulal Nathalal Kalariya Charitable Trust to carry out research project as partial fulfillment of graduate degree programme.

Keywords

  • Apoptosis
  • Cadmium
  • Cataract
  • Lens epithelial cells
  • Oxidative stress

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