Cytotoxic effects of cadmium and zinc co-exposure in PC12 cells and the underlying mechanism

Abstract

Cadmium (Cd) is a well studied inducer of cellular necrosis and apoptosis. Zinc (Zn) is known to inhibit apoptosis induced by toxicants including Cd both in vitro and in vivo. The mechanism of Zn-mediated protection from Cd-induced cytotoxicity is not established. In this study, we aimed to understand the effects of Zn on Cd-induced cytotoxicity and apoptosis using PC12 cells. Cell viability and DNA fragmentation assays in PC12 cells exposed to Cd and/or Zn revealed that Cd (5 and 10 μmol/L) alone induced significant cell death, and co-exposure to Zn (5, 10, and 100 μmol/L) for 48 h had a protective effect. Assessment of intracellular free sulfhydryl levels and lactate dehydrogenase activity suggested that Cd (10 μmol/L) induced oxidative stress and disrupted cell membrane integrity. Addition of Zn (10 and 100 μmol/L) reduced Cd-mediated cytotoxicity. Changes in expression of the apoptotic factors Bax, Bcl-2, Bcl-x, and cytochrome c were measured via western blot and expression of caspase 9 was detected via reverse transcriptase polymerase chain reaction. Western blots showed that Zn (10 and 100 μmol/L) suppressed Cd-induced apoptosis (10 μmol/L) by reducing cytochrome c release into the cytosol, and downregulating the proapoptotic protein, Bax. In addition, expression of caspase 9 was lower in Cd (5 μmol/L)-treated PC12 cells when co-treated with Zn (2 and 5 μmol/L). These findings suggest that the effective inhibition of Cd-induced apoptosis in PC12 cells by Zn might be due to suppression of mitochondrial apoptosis pathway and inhibition of Cd-induced production of reactive oxygen species.

Haematological Profile and Some Reproductive Indices of Male Albino Rats Treated with Ethanolic Stem Bark Extract of Picralima nitida

“…However, it was observed that the rats given 2.5 mg/kg BW of cadmium chloride had a significantly fewer WBC compared to the rest of the experimental groups. This could be attributed to the cytotoxic property of this compound [42]. Congruent with our finding, sub chronic treatment with cadmium has been reported to cause leucopenia in wistar rats [43,44].…”

Selenium against lead-induced apoptosis in chicken nervous tissues via mitochondrial pathway

“…The induction of p53 leads to Cyt c release [ 46 ]. The release of Cyt c activates Caspase-3 [ 10 ]. The activation of Caspase-3 induces apoptosis [ 10 ].…”

“…Excess Pb caused human and animal neurotoxicity, including behavioral deficit in herring gull brains [ 6 ], hippocampus damage and apoptosis in rat adrenal medulla pheochromocytoma cells (PC 12) [ 7 ], oxidative stress and apoptosis in human neuroblastoma cells [ 8 ], and apoptosis in rat brains [ 9 ]. Cadmium (Cd) disrupted mitochondrial membrane integrity and triggered release of mitochondrial proteins cytochrome c (Cyt c) into cytosol, then Cyt c activated Caspase-3, finally apoptosis occurred in PC 12 [ 10 ]. Pb induced apoptosis via mitochondrial pathway in rat proximal tubular cells [ 11 ].…”

Possible ameliorative effect of nano-chocolate fortified with zinc on the hepatic and testicular toxicity induced by cadmium on male Swiss albino mice: histopathological and histomorphometrical studies

“…*P < 0.05 is significant **P < 0.01 is highly significant 2010; Vasiljeva, Berzina, & Remeza, 2011;Vasiljeva, Smirnova, Basova, & Babarykin, 2018). Cadmium induced oxidative damage to the cellular macromolecules and cellular structures (Curcic et al, 2014;Rahman et al, 2017). On another hand, treatment with cadmium and nano-chocolate fortified with zinc improved histopathological lesions and morphometrical changes in the hepatic and testicular tissues induced by cadmium.…”