title: Chronic Exposure to Low-Level Cadmium in Diabetes: Role of Oxidative Stress and Comparison with Polychlorinated Biphenyls.
abstract: Among the most important physiological functions, maintenance of the oxidation reduction equilibrium in cells stands out as a major homeostatic event. Many environmental contaminants efficiently trap cellular reducing compounds, but the actual importance of this mode of toxicity is far from being precisely known. This statement applies to cases of slowly developing chronic diseases, such as neurodegenerations, diabetes, and many others. The involvement of oxidative challenge in diabetes is considered in connection with chronic dietary exposure to low-level concentrations of cadmium. Comparison is made with polychlorobiphenyl molecules (PCB): they are structurally unrelated to cadmium, they preferentially distribute into different organs than cadmium, and they follow different metabolic pathways. Yet, they have also pro-oxidative properties, and they are associated with diabetes. Since neither cadmium nor PCB is a direct oxidant, they both follow indirect pathways to shift the redox equilibrium. Thus, a difference must be made between the adaptable response of the organism, i.e. the anti-oxidant response, and the irreversible damage generated by oxidizing species, i.e. oxidative damage, when exposure occurs at low concentrations. The approximate border between high and low levels of exposure is estimated in this review from the available relevant data, and the strengths and weaknesses of experimental models are delineated. Eventually, chronic low level exposure to these contaminants sparks cellular responses setting ground for dysfunction and disease, such as diabetes: oxidative damage is an accompanying phenomenon and not necessarily an early mechanism of toxicity.
authors.forename: Adeline
authors.initials: A
authors.lastname: Jacquet
authors.forename: Fayçal
authors.initials: F
authors.lastname: Ounnas
authors.forename: Marine
authors.initials: M
authors.lastname: Lénon
authors.forename: Josiane
authors.initials: J
authors.lastname: Arnaud
authors.forename: Christine
authors.initials: C
authors.lastname: Demeilliers
authors.affiliation: LBFA-INSERM U1055, University Grenoble Alpes, CS 40700, F-38058 Grenoble Cedex 9, France. jean-marc.moulis@cea.fr.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Moulis
mesh_terms: D000818:Animals; D002104:Cadmium / Q000008:administration & dosage* / Q000633:toxicity; D003920:Diabetes Mellitus / Q000209:etiology / Q000503:physiopathology*; D004781:Environmental Exposure / Q000009:adverse effects; D006801:Humans; D016877:Oxidants / Q000008:administration & dosage / Q000633:toxicity; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000008:administration & dosage* / Q000633:toxicity
chemical_list: D016877:Oxidants; D002104:Cadmium; D011078:Polychlorinated Biphenyls