Toxicology letters
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Garlic and garlic extracts are used as seasonings and are generally considered beneficial to human health, which include antioxidant and neuroprotective properties in neurological disorders. In the present study, we examined the effects of garlic sulfur components on the proliferation of neural progenitor cells (NPCs) and hippocampal neurogenesis. Of the sulfur compounds extracted, diallyl disulfide (DADS) significantly suppressed the proliferation of NPCs, whereas other sulfur containing components had no effect. ⋯ Furthermore, DADS decreased levels of hippocampal BDNF, phosphorylated CREB signaling, and phosphorylated ERKs, which are known to be related to hippocampal neurogenesis and NPCs proliferation. In addition, DADS induced significant memory defects as compared with controls. We report that DADS may have adverse effects on hippocampal neurogenesis and neurocognitive functions by modulating ERK and BDNF-CREB signaling, and suggest that the advisability of consuming large amounts of garlic products should be considered, particularly during the period of neural growth.
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Therapeutically induced autophagic cell death has been proven to be effective in cases of solid tumors. The dual phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor NVP-BEZ235 possesses antitumor activity against solid tumors. Inhibition of mTOR has been shown to elicit autophagy. In this study, we examined the antiproliferation and autophagic activities of NVP-BEZ235 in parental and cisplatin-resistant urothelial carcinoma (UC) cells. ⋯ We demonstrated that NVP-BEZ235 inhibits UC cell proliferation by activating autophagic flux and cell cycle arrest, but does not induce apoptotic cell death. Our findings suggest that the anticancer efficacy of NVP-BEZ235 is due to autophagic flux and co-treatment with CQ counteracts the cytotoxic effect.
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Ketamine is widely used as an anesthetic, analgesic, and sedative in pediatric clinical practice and it is also listed as an illicit drug by most countries. Recent in vivo and in vitro animal studies have confirmed that ketamine can induce neuronal cell death in the immature brain, resulting from widespread neuronal apoptosis. ⋯ Taken together, these findings identify a novel complication associated with ketamine use in premature infants, term newborns, and pregnant women. Recent data on the developmental neurotoxicity of ketamine are reviewed with proposed future directions for evaluating the safety of ketamine in these patient populations.
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The long chain omega-3 polyunsaturated fatty acids (PUFA) have been reported to exert anti-cancer effects. At this study we tested the effect of the omega-3 PUFA, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), on pre-malignant keratinocytes growth in the well-characterised human pre-malignant epidermal cell line, HaCaT and attempted to identify a PUFA serum antagonist. Both EPA and DHA inhibited HaCaT growth and induced apoptosis. ⋯ None of the numerous serum growth factors present in FBS or the antioxidant n-tert-butyl-α-phenylnitrone could inhibit the PUFA-induced cytotoxicity. In contrast, bovine and human albumin (0.1-0.3%, w/v) significantly antagonized the growth inhibitory and apoptosis-inducing effects of PUFA. In conclusion, we have shown for the first time that omega-3 PUFA inhibit the growth and induce apoptosis of pre-malignant keratinocytes and identified albumin as a major antagonistic factor in serum that could limit their effectiveness at pharmacologically-achievable doses.
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Cyclosporine A (CsA) nephrotoxicity has been linked to reactive oxygen species (ROS) production in renal cells. We have demonstrated that the antioxidant Vitamin E (Vit E) abolished renal toxicity in vivo and in vitro models. As one of the main sources of intracellular ROS are mitochondria, we studied the effects of CsA on several mitochondrial functions in LLC-PK1 cells. ⋯ Furthermore, CsA altered the mitochondrial dynamics, inducing an increase in mitochondrial fission; CsA increased the expression of dynamin related protein 1 (Drp1) that contributes to mitochondrial fission, and decreased the expression of mitofusin 2 (Mfn2) and optic atrophy protein 1 (Opa1), proteins involved in the fusion process. All these phenomena were related to apoptosis. These effects were inhibited when cells were treated with the antioxidant Vit E suggesting that they were mediated by the synthesis of ROS.