Role of L-arginine and metallothioneins in lymphocyte apoptosis after chronic exposure to inorganic mercury

Mercury induces lymphocyte apoptosis. A role for metallothioneins (MTs) has been hypothesized in the response to the cell oxidative stress related to apoptosis. Binding of these small proteins to essential metals (Zn++ e Cu++) induces their homeostatic equilibrium, while binding to heavy metals prevents oxidative damage and apoptosis. The antioxidant activity of nitric oxide (NO), the end-product of L-arginine transformation, also participates in the complex molecular reactions taking place in the course of noxious stimulation. The aim of the work was to assess the correlation among degree of apoptosis, metallothionein expression, and NO synthase (NOS) activity on spleen cells from different mouse strains (C57BL/6 wild-type, MT-null and transgenic MT-overexpressing mice) during chronic mercury intoxication. HgCl2 treated mice exhibited an increased rate of apoptosis and an increment of Fas-expressing lymphocytes, whereas NOS activity displayed an opposite behaviour. MTs were overexpressed in the mouse strains that could produce them. Supplementation with oral L-arginine partly restored pre-stimulation conditions, albeit to a lesser degree in MT-null mice. Data support the involvement of MTs in the apoptotic process induced by chronic mercury exposure and the benefit of supplementation with oral L-arginine on metabolism and lymphocyte activity after intoxication.