Melatonin ameliorates nickel induced autophagy in mouse brain: Diminution of oxidative stress

Nickel (Ni) is a neurotoxic environmental pollutant. Oxidative stress is thought to be the main mechanism behind the development of Ni neurotoxicity. Melatonin (Mt) has significant efficacy as an antioxidant. In this paper, we investigated the damage that Ni causes to the autophagy of the nervous system. Furthermore, Mt has can intervene upon the damage caused by Ni, which can protect the nervous system. Herein, we randomly divided 80 8-week-old male wild-type C57BL/6 N mice into four groups, including the C group, Ni group, Mt group, and Mt+Ni group. Ni was gavaged at a concentration of 10 mg/kg, while was Mt was administered at a concentration of 2 mg/kg for 21 days at 0.1 ml/10 g body weight of the mice. Histopathological and ultrastructural observations demonstrated altered states, such as neuronal atrophy, as well as typical autophagic features in the Ni group. Mt was able to intervene effectively in Ni-induced neurotoxicity. The antioxidant capacity assay also demonstrated that Ni can lead to a large amount of reactive oxygen species (ROS) production within the mouse brain. Furthermore, the same Mt was effective at reducing ROS production. In order to further illustrate this point, we added the broad-spectrum phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 to NS20Y cells. The presence of inhibitors effectively demonstrates that, within the PI3K/AKT/mTOR pathway, autophagy occurs. In conclusion, these data suggest that Ni causes oxidative stress damage and induces autophagy within the mouse brain by inhibiting the PI3K/AKT/mTOR pathway, and that Mt can effectively alleviate the oxidative stress caused by Ni, and reducing Ni induces autophagy in the mouse brain through the PI3K/AKT/mTOR pathway.

Automated summary

This study found that oxidative stress is the main mechanism behind nickel neurotoxicity. Nickel induced oxidative stress damage and autophagy in the mouse brain, but melatonin was able to intervene and protect the nervous system.