Sodium/calcium overload and Sirt1/Nrf2/OH-1 pathway are critical events in mercuric chloride-induced nephrotoxicity.

Mercury (Hg), a significant toxic metal for nephrotoxicity, can be found in food (vegetable and seafood) and drinking water by contamination. Oxidative stress is involved in inorganic Hg-induced nephrotoxicity, but the Sirtuin1 (Sirt1)/Nrf2/OH-1 pathway and sodium (Na)/calcium (Ca) ions actions in mercuric chloride (HgCl)-induced nephrotoxicity remains unclear to date. In this study, Kunming mice were treated HgCl (5 mg/kg) for 24 h to evaluate potential mechanism. Here, along with Sirt1 activation, pale kidney, hisologic conditions, typical apoptotic changes and TUNEL positive nuclei were observed under acute HgCl exposure. Specifically, although HgCl increased the expression of Nrf2, Keap1, OH-1 and NQO1, the mRNA levels of GSS, GCLC and GCLM showed no significant alterations in mice kidney. Moreover, mice exposed to HgCl decreased the concentrations of Mg, K, P, Mn, Fe, Zn, and elevated Na, Ca, Cu and Se in kidney. It was also observed that HgCl suppressed the ATPases (Na-K-ATPase, Ca-ATPase, Mg-ATPase and Ca-Mg-ATPase) activities and decreased the mRNA levels of Atp1a1, Atp1a2 in the kidney. Further study showed that HgCl elevated Na concentrations by markedly increased the mRNA levels of Na transporter. The present study revealed that HgCl induced Sirt1/Nrf2/OH-1 pathway activation while did not inhibit apoptosis in kidney of mice. Additionally, HgCl regulates Na concentrations, which might create secondary disorders in absorption and excretion of other ions. Altogether we assume that Sirt1/Nrf2/Na/Ca pathway might be a potential therapeutic target for treating acute HgCl induced nephrotoxicity.