Title:Chronic Exposure to Low-Level Cadmium in Diabetes: Role of Oxidative Stress and Comparison with Polychlorinated Biphenyls
Volume: 17
Issue: 12
Author(s): Adeline Jacquet, Fayçal Ounnas, Marine Lénon, Josiane Arnaud, Christine Demeilliers and Jean-Marc Moulis
Affiliation:
Keywords:
Cadmium, diabetes, insulin, oxidative stress, polychlorinated biphenyl compounds (PCB), low dose, biomarkers,
risk assessment.
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.
