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.

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Background: Fructose intake has been correlated with increased prevalence of metabolic disorders including hypertension. In pregnant rats, fructose intake has been reported to have adverse effects on the health of its offspring. This study investigated the effects of gestational maternal fructose consumption and if supplementation with melinjo seed extracts to the maternal diet during lactation could benefit the offspring in later life. Methods: Pregnant rats were randomly divided into three groups: untreated (CC), fructose-treated (FC), and fructose and melinjo-treated (FM). FC and FM groups received 100 g/L of D(-)-fructose solution by means of the drinking water during gestation while CC received normal drinking water. During lactation, CC and FC groups were given standard commercial laboratory diet, while the FM group was given commercial laboratory diet with 0.1% melinjo seed extracts. After weaning, the offspring were given normal drinking water and standard commercial diet until week 17. The blood pressure of the offspring was monitored until the 16th week. During week 17, the offspring were killed, and the kidneys were collected and analyzed. Results: The level of renal phosphorylated AMP-activated protein kinase (pAMPK) in FM of 17-week female offspring was significantly higher compared with FC and CC groups. Maternal fructose intake down-regulated the renal endothelial isoform of nitric oxide synthetase expression in FC and maternal melinjo seed extract consumption maintained renal endothelial isoform of nitric oxide synthetase expression in FM of 17-week female offspring. In addition, maternal melinjo seed extract intake during lactation lowered the systolic blood pressure in FM of 17-week female offspring. Conclusion: Female offspring were more vulnerable to the effects of placental fructose and melinjo seed extracts, suggesting sex-specific sensitivities. In summary, our data show that melinjo seed extract consumption during lactation improved vasodilation and attenuated the development of hypertension in the 17-week female offspring of fructose-fed pregnant rats.

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