Antioxidant potential and gap junction-mediated intercellular communication as early biological markers of mercuric chloride toxicity in the MDCK cell line

Abstract

In this study, the early nephrotoxic potential of mercuric chloride (HgCl 2 ) has been evaluated in vitro, by exposing a renalderived cell system, the tubular epithelial Madin-Darby canine kidney (MDCK) cell line, to the presence of increasing HgCl 2 concentrations (0.1-100 mm) for different periods of time (from 4 to 72 h). As possible biological markers of the tubular-specific toxicity of HgCl 2 in exposed-MDCK cultures we analysed: (i) critical biochemical parameters related to oxidative stress conditions and (ii) gap-junctional function (GJIC). HgCl 2 cytotoxicity was evaluated by cell-density assay. The biochemical analysis of the pro-oxidant properties of the mercuric ion (Hg ) was performed by evaluating the effect of the metal salt on the antioxidant status of the MDCK cells. The cell glutathione (GSH) content and the activity of glutathione peroxidase (Gpx) and catalase (Cat), two enzymes engaged in the H 2 O 2 degradation, were quantified. HgCl 2 influence on MDCK GJIC was analysed by the microinjection/dye-transfer assay. HgCl 2 -induced morphological changes in MDCK cells were also taken into account. Our results, proving that subcytotoxic (0.1-10 mm) HgCl 2 concentrations affect either the antioxidant defences of MDCK cells or their GJIC, indicate these critical functions as suitable biological targets of early mercury-induced tubular cell injury. #

Mercury modulates interplay between IL-1β, TNF-α, and gap junctional intercellular communication in keratinocytes: mitigation by lycopene

“…One important mechanism could be that the lycopene in the oleoresin is having an important effect on oxidative stress in/among the cells. Several studies have indicated that oxidative stress is induced in many cell types by mercury (i.e., see Aleo et al, 2002;Han et al, 2007;Park and Park, 2007) although, to date, reports of mercury-induced oxidative stress in keratinocytes are lacking. Ongoing studies in our laboratory have indicated that there is, in fact, a mercury-induced oxidative stress in keratinocytes and that this outcome paralleled reductions in GJIC and in formation of pro-inflammatory cytokines in these cells (unpublished data).…”

Connexin43 Hemichannels Contribute to Cadmium-Induced Oxidative Stress and Cell Injury

“…Gap junctions, on the one hand, are subjected to the regulation of oxidative stress (1,(3)(4)(5). On the other hand, they impact cell responses to oxidative stress-initiated cell injury (2,19,32).…”

Renal oxidative stress and renal CD8+ T-cell infiltration in mercuric chloride-induced nephropathy in rats: role of angiotensin II

“…In this process, a shift to the former is termed as oxidative stress. Mercuric chloride (HgCl 2 ) is nephrotoxic in rats and affects the pars recta (S3 segment) of the proximal tubule (Stacchiotti et al 2003), inducing a necrosis that seems to be mediated by oxidative damage (Aleo et al 2002;Shimojo et al 2002). The oxidative stress induced by HgCl 2 is mediated by a strong affinity + cells in tissues from all HgCl 2 -treated rats relative to in Group VI control rat tissues (untreated, saline gavaged) were found.…”

“…Mercury is excreted almost exclusively via the kidney; thus, renal exposure to mercury is unavoidable and subsequent toxicity commonly evolves in the kidney (Madden & Fowler 2000). Renal mercury chloride (HgCl 2 )-induced damage has been studied using experimental models of nephropathy, showing that the toxic effects of HgCl 2 in the kidney are related to inflammatory events and/or oxidative stress (Ghielli et al 2000;Aleo et al 2002;Shimojo et al 2002;de Greef et al 2003;Stacchiotti et al 2003).…”