Effect of thimerosal on Ca2+ movement and viability in human oral cancer cells

Abstract

<jats:p> The effect of thimerosal on cytosolic free Ca<jats:sup>2+</jats:sup> concentrations ([Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub> ) in human oral cancer cells (OC2) is unclear. This study explored whether thimerosal changed basal [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub> levels in suspended OC2 cells using fura-2. Thimerosal at concentrations between 1and 50 μM increased [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub> in a concentration-dependent manner. The Ca<jats:sup>2+</jats:sup> signal was reduced partly by removing extracellular Ca<jats:sup> 2+</jats:sup>. Thimerosal-induced Ca<jats:sup>2+</jats:sup> influx was not blocked by L-type Ca<jats:sup>2+</jats:sup> entry inhibitors and protein kinase C modulators (phorbol 12-myristate 13-acetate [PMA] and GF109203X). In Ca<jats:sup>2+</jats:sup>-free medium, 50 μM thimerosal failed to induce a [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub> rise after pretreatment with thapsigargin (an endoplasmic reticulum Ca<jats:sup>2+</jats:sup> pump inhibitor). Inhibition of phospholipase C with U73122 did not change thimerosal-induced [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub> rises. At concentrations between 5 and 10 μM, thimerosal killed cells in a concentration-dependent manner. The cytotoxic effect of 8 μM thimerosal was potentiated by prechelating cytosolic Ca<jats:sup>2+</jats:sup> with the Ca<jats:sup>2+</jats:sup> chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetate/acetomethyl (BAPTA/ AM). Flow cytometry data suggested that 1—7 μM thimerosal-induced apoptosis in a concentration-dependent manner. Collectively, in OC2 cells, thimerosal-induced [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub> rises by causing phospholipase C-independent Ca<jats:sup>2+</jats:sup> release from the endoplasmic reticulum and Ca<jats:sup>2+</jats:sup> influx through non—L-type Ca<jats:sup>2+</jats:sup> channels. Thimerosal killed cells in a concentration-dependent manner through apoptosis. </jats:p>

D-Pinitol Promotes Apoptosis in MCF-7 Cells via Induction of p53 and Bax and Inhibition of Bcl-2 and NF-κB

“…It is an active low-molecular cyclitol isolated from the seed coat, cotyledon and embryo axis of soybean seeds (Kuo et al, 2009). Moreover, as a natural therapeutic agents it has gained much attention due to their diverse biological activities such as inhibition of the T-helpercell-1 response, antiviral, larvicidal, antiinflammatory, antihyperlipidemic, cardioprotective, inhibition of ovalbumin-induced airway inflammation and antioxidant (Sethi et al, 2008;Sivakumar et al, 2010).…”

Thimerosal in childhood vaccines contributes to accumulating mercury toxicity in the kidney

“…There is also evidence of increasing intracellular Ca 2þ through thimerosal exposure in several non-kidney cell types (Pintado et al 1995;Chen, Harada, and Yamashita 1998;Kuo et al 2009). It is known that etHg is less neurotoxic than meHg in adult male and female rats (Magos 1986), but the potency of etHg/thimerosal in vitro to induce the cytotoxicity through rising intracellular levels of Ca 2þ on brain neurons from infant rats appears to be similar to that of meHg ).…”

“…By using different approaches, several groups demonstrated that both inorganic Hg and etHg/thimerosal induce apoptosis in several non-kidney cell lines (Guo et al 1998;Goering et al 1999;Baskin, Ngo, and Didenko 2003;Issa et al 2003;Humphrey et al 2005;Kuo et al 2009;Li et al 2012). Thimerosal was shown to induce DNA and membrane damage and also caspase-3-dependent apoptosis in the human neuronal and fibroblasts (Baskin, Ngo, and Didenko 2003), to activate caspase-9 and caspase-3 in T cells and human neuroblasts (Makani et al 2002;Humphrey et al 2005), and to activate the c-Jun N-terminal kinase pathway in neuroblastoma cells (Herdman et al 2006).…”

Avaliação da distribuição, metabolismo e nefrotoxicidade do timerosal - um conservante a base de mercúrio usado em vacinas - utilizando modelos in vivo e in vitro

“…Utilizando diferentes abordagens, vários grupos sugerem que o timerosal induz apoptose em diversas linhagens de células não-renais (BASKIN, et al, 2003;HUMPHREY, et al, 2005;KUO, et al, 2009;LI, et al, 2012). Até o momento, o único estudo que avaliou um potencial mecanismo de nefrotoxicidade do timerosal no tecido renal foi realizado por JAN e colaboradores que demonstraram que este agente organomercurial induz aumento de cálcio intracelular, em células renais caninas (Madin Darby canine kidney) (JAN, et al, 2003).…”

“…Diferentes estudos desenvolvidos em várias linhagens de células não-renais têm demonstrado que o timerosal induz apoptose (LI, et al, 2012;KUO, et al, 2009;HUMPHREY, et al, 2005;BASKIN, et al, 2003 -ACHANZAR, et al, 1996;GUO, et al, 1998;CARRANZA-ROSALES, et al, 2005;LEE, et al, 2006;TARABOVA, et al, 2006;SUTTON;TCHOUNWOU, 2007;KANDA, et al, 2008). No entanto, em relação a marcadores apoptóticos após exposição ao EtHg ou timerosal, no tecido renal não foram encontradas evidências na literatura.…”