Hydroxyapatite nanoparticles (HAP NPs) are widely used for preparations of biomedical and biotechnological fields such as drug delivery, gene therapy, and molecular imaging. However, the current toxicological knowledge about HAP NPs is relatively limited. The present study was designed to investigate the toxicity potentials of various concentrations (0–1000 µg cm−2) of HAP NPs in cultured primary rat hepatocytes. Cell viability was detected by 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) release, while total antioxidant capacity (TAC) and total oxidative stress (TOS) levels were determined to evaluate the oxidative injury. The DNA damage was also analyzed via scoring liver micronuclei rates and determining 8-oxo-2-deoxyguanosine (8-OH-dG) levels. The results of MTT and LDH assays showed that the higher concentrations of dispersed HAP NPs (300, 500, and 1000 µg cm−2) decreased cell viability. Also, HAP NPs increased TOS (500 and 1000 µg cm−2) levels and decreased TAC (300, 500, and 1000 µg cm−2) levels in cultured hepatocytes. On the basis of increasing doses, the NPs as depending on dose caused significant increases of the number of micronucleated hepatocytes and 8-OH-dG levels as compared to control culture. Furthermore, the highest concentration of HAP NPs (1000 µg cm−2) exhibited cytotoxic activity. Based on these results, HAP NPs have a dose-dependent toxic effect in rat hepatocytes. Further extensive research in this field is promising and reasonable.

In this experimental design, we explored the neuroprotective potential of zingiberene (ZGB), a monocyclic sesquiterpene, in hydrogen peroxide (H2O2)-induced toxicity in newborn rat cerebral cortex cell cultures for the first time. The rats were exposed to H2O2 for 6 h to determine the oxidative stress levels. To evaluate cell viability, both 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays were carried out. Total antioxidant capacity (TAC) and total oxidative stress (TOS) parameters were used to evaluate oxidative changes. Besides determining 8-hydroxy-2-deoxyguanosine (8-OH-dG) levels in vitro, single-cell gel electrophoresis was also performed to measure the resistance of neuronal DNA to H2O2- exposed rats. Our results showed that survival and TAC levels of the cells decreased, while TOS, 8-OH-dG levels and the mean values of the total scores of cells showing DNA damage increased in the H2O2 alone-treated cultures. But pretreatment of ZGB suppressed the cytotoxicity, genotoxicity and oxidative stress that were increased by H2O2. Based on these observations, it is suggested that the sesquiterpene ZGB can be used as a novel and natural potential therapeutic in counteracting oxidative damages in the field of neurodegenerative disorders.

Backbone Linkage. -The new glutathione analogues (I), characterized by the replacement of central cysteine with either serine or aspartic acid and containing a urethanic fragment as isosteric substitution of the scissile γ-glutamylic junction, are synthesized in good overall yields using solution procedures by stepwise elongation of the peptide chain in the C-to-N direction. The results of the biological studies are discussed. -(CACCIATORE, I.; CACCURI, A. M.; DI STEFANO, A.; LUISI, G.; NALLI, M.; PINNEN*, F.; RICCI, G.; SOZIO, P.; Farmaco 58 (2003) 9, 787-793; Ist. Sci. Farm.,

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