A Review on the Biochemical and Molecular Mechanisms of Phthalate-Induced Toxicity in Various Organs with a Focus on the Reproductive System

Phthalates are a large group of chemicals, used in plasticizers and industrial solvents, to make them flexible and soluble, especially when these materials are applied in the production of toys, medical equipment and drugs coverings. It seems that phthalates induce multi-organ damage through a number of mechanisms such as oxidative stress via generation of Reactive Oxygen Species (ROS), DNA damage, lipid peroxidation, disrupting cell function and also altering the expression and activity of the most important antioxidant enzymes. In this study, we reviewed the recent publications that evaluated the contribution of oxidative stress in phthalate toxicity. Alteration of antioxidant enzymes such as a reduced SOD (Cu/Zn superoxide dismutase) activity as well as an increased CAT (catalase) function normally occur and can be observed particularly with higher doses of phthalates. Moreover, these compounds decrease GPX (glutathione peroxidase) and GST (glutathione S-transferase) activities. Nevertheless, controversy is found in the levels of cellular antioxidants like SOD showing a reduction in many organs like liver, kidney and reproductive system, whereas, its increase has been reported in a few studies. In summary, among various organs, reproductive system seems was affected further by oxidative stress through disruption of spermatogenesis, inducing mitochondrial dysfunction in gonocytes, impairment of cellular redox mechanism and increasing peroxiredoxin 3 and cycloxygenase 2 levels in spermatocytes. The phthalates are being replaced in some countries by other safe plasticizers.