Sodium fluoride promotes apoptosis by generation of reactive oxygen species in human lymphocytes.

Fluoride generated the attention of toxicologists due to its deleterious effects at high concentrations in human populations suffering from fluorosis and with in vivo experimental models. Interest in its undesirable effects has resurfaced due to the awareness that this element interacts with cellular systems even at low doses. This study focused on examining the adverse effects of inorganic fluoride (NaF) on human lymphocyte cells in vitro. Mitochondrial function, oxidative stress, cell cycle progression, and mode of cell death were combined with genotoxic endpoints. Data demonstrated that NaF at lower concentrations, although not significantly cytotoxic and genotoxic, induced oxidative stress leading to apoptotic cell death. The results also suggested that at low concentrations (<1 µg/ml), NaF may affect cell cycle progression. Taken together, our findings confirm earlier reports on mechanisms involved in NaF-induced apoptosis.

Comprehensive analysis of fly ash induced changes in physiological/growth parameters, DNA damage and oxidative stress over the life cycle of Brassica juncea and Brassica alba.

Fly ash (FA) being a heterogeneous mixture of heavy metal affects plant system in various ways. Previous studies have shown bioaccumulation of toxic metals in the plants and disturbance in cellular activities. Here, we have studied the impacts of FA treatment through the life cycle of economically important, annual crop plant mustard (Brassica juncea and Brassica alba). Result revealed that FA did not alter germination rate and photosynthetic pigment levels. Tolerance index of B. juncea was higher compared to B. alba. Seed setting was significantly affected by FA in B. alba. Significant increase in DNA damage was observed in both B. alba and B. juncea. Proline accumulation was significantly higher in B. alba. In B. juncea catalase activity and reduced glutathione content declined in initial days which were restored at the end of experimental period. Significant decrease in non-enzymatic antioxidants was noted in B. alba. Higher accumulation of Pb and As was noted in shoot of B. juncea and in B. alba Cu, Pb, Cr and As accumulated in shoots. As observed from these results, both plants could translocate certain toxic heavy metals from roots to the shoot which affected the physiological and biochemical balance and induced genotoxic response.

Mycobacterial heat shock protein 65 mediated metabolic shift in decidualization of human endometrial stromal cells.

Successful implantation is dependent on the appropriate decidualization of endometrial stromal cells for the establishment of pregnancy in women. Mycobacterial heat shock protein 65 (HSP65) is involved in pathogenesis of the genital tuberculosis (GTB), one of the common causes of infertility in emerging countries. Though implantation failure appears to be the major cause, understanding the status of decidualizaiton process in women diagnosed with GTB has not been thoroughly addressed. We, therefore, explored the effect of HSP65 protein on the endometrial cell metabolism during in vitro decidualization. In order to identify the cellular metabolism of decidual cells with and without HSP65 treatment, proton NMR based characterization of metabolites extracted from cells and culture media were performed. In presence of HSP65, significant reduction in the decidual phenotype of endometrial stromal cells and prolactin expression is suggestive of impairment in decidualization. The intracellular and extracellular metabolic changes in HSP65 treated endometrial stromal cells produced a distinct pattern, reflecting the interaction between the protein and cellular metabolism. HSP65 mediated dysregulation in cellular metabolism is associated with poor decidualization. Besides enriching the present knowledge on metabolic changes underlying stromal cells decidualization, these findings assist in identifying potential molecular causes for decidualization failure in GTB women.

Cyto-genotoxicity and oxidative stress induced by zinc oxide nanoparticle in human lymphocyte cells in vitro and Swiss albino male mice in vivo.

ZnO-np has immense potential and application in cosmetic and health care sectors. Hence it was imperative to assess the toxicity/safety of these nanoparticles. In this study, we have evaluated the effects of ZnO-np in human peripheral blood mononuclear cells (PBMCs) in vitro and in Swiss albino male mice in vivo for cyto-genotoxicity and oxidative damage. In vitro results showed that ZnO-nps were weakly genotoxic, induced significant decrease in mitochondrial membrane potential and was capable of ROS generation, leading to apoptosis. In bone marrow cells in vivo, reduction of mitochondrial membrane potential (MMP), increased oxidative stress and G0/G1 cell cycle arrest was observed along with chromosome aberrations and micronuclei formation. In liver cells DNA damage and induction of oxidative stress with concurrent decrease in inhibition of antioxidant enzymes were noted. These in vitro and in vivo results demonstrated that ZnO-np induced genotoxic response and ROS production leading to apoptotic cell death and established a good co-relation between the two biological systems. More importantly, the results stress on the need of multiple endpoint assay-approaches, with an in vitro-in vivo study design to assess nanoparticle toxicology.

Effects of ZnO nanoparticles in plants: Cytotoxicity, genotoxicity, deregulation of antioxidant defenses, and cell-cycle arrest.

Cytotoxicity, genotoxicity, and biochemical effects were evaluated in the plants Allium cepa, Nicotiana tabacum, and Vicia faba following exposure to ZnO nanoparticles (np; diameter, ∼85nm). In the root meristems of Allium cepa cells, we observed loss of membrane integrity, increased chromosome aberrations, micronucleus formation, DNA strand breaks, and cell-cycle arrest at the G2/M checkpoint. In Vicia faba and Nicotiana tabacum, we observed increased intracellular ROS production, lipid peroxidation, and activities of some antioxidant enzymes. TEM images revealed gross morphological alterations and internalization of the np. Our findings provide evidence of ZnO np toxicity, characterized by deregulation of components of ROS-antioxidant machinery, leading to DNA damage, cell-cycle arrest, and cell death. These plants, especially Allium cepa, are reliable systems for assessment of np toxicology.

Vetiver oil (Java) attenuates cisplatin-induced oxidative stress, nephrotoxicity and myelosuppression in Swiss albino mice.

Clinical efficacy of the widely used anticancer drug cisplatin is limited due to its adverse side effects in normal tissues mediated by oxidative stress. This study was aimed to investigate the protective effects of vetiver acetate oil, Java (VO) against cisplatin-induced toxicity in Swiss albino mice. The ameliorating potential was evaluated by orally priming the animals with VO at doses 5, 10 or 20 mg/kg bw for 7 days prior to cisplatin treatment. Acute toxicity in mice was induced by injecting cisplatin (3 mg/kg bw) intraperitoneally for 5 consecutive days. Significant attenuation of renal toxicity was confirmed by histopathological examination, lowered levels of serum blood urea nitrogen, creatinine and reduced DNA damage. VO also compensated deficits in the renal antioxidant system. VO intervention significantly inhibited DNA damage, clastogenic effects, and cell cycle arrest in the bone marrow cells of mice. Hematological parameters indicated attenuation of cisplatin-induced myelosuppression. Overall, this study provides for the first time that VO has a protective role in the abatement of cisplatin-induced toxicity in mice which may be attributed to its antioxidant activity.

Evaluation of toxicity of essential oils palmarosa, citronella, lemongrass and vetiver in human lymphocytes.

The present investigation was undertaken to study the cytotoxic and genotoxic potential of the essential oils (palmarosa, citronella, lemongrass and vetiver) and monoterpenoids (citral and geraniol) in human lymphocytes. Trypan blue dye exclusion and MTT test was used to evaluate cytotoxicity. The genotoxicity studies were carried out by comet and DNA diffusion assays. Apoptosis was confirmed by Annexin/PI double staining. In addition, generation of reactive oxygen species was evaluated by DCFH-DA staining using flow cytometry. The results demonstrated that the four essential oils and citral induced cytotoxicity and genotoxicity at higher concentrations. The essential oils were found to induce oxidative stress evidenced by the generation of reactive oxygen species. With the exception of geraniol, induction of apoptosis was confirmed at higher concentrations of the test substances. Based on the results, the four essential oils are considered safe for human consumption at low concentrations.