[A COMPARATIVE EVALUATION OF THE EFFECT OF DENTURES FROM VARIOUS MATERIALS ON THE ORAL CAVITY'S IMMUNOLOGICAL AND REDOX-DEPENDENT HOMEOSTASIS].

The purpose of our study was a comparative analysis of the effect of dentures from various materials on the immunological and redox-dependent homeostasis of the oral cavity. We studied 60 patients with removable dentures made based on plastics Prothyl Hot, Vertex BasiQ 20 (differing by polymerization regime) and elastic thermoplastic polymer Perflex Flexi Nylon. The control group consisted of 15 volunteers with a practically healthy oral cavity, who did not use dentures. Saliva collected on an empty stomach in a glass tube without the use of a stimulator before the establishment of a denture and 3 days and 1 month after. The content of the protein P-53 in saliva determined by immunoenzymatic assay with use of "Cusabio" reagent. The cytokines (IL1ß, IL10) content in saliva was determined immunoenzymatic assay. To determine the redox balance in the saliva of patients, the lipoperoxydradicals content (LOO.) content (by EPR method, using the spin-labeled α-phenyl-tertbutylnitron (PBN) (SIGMA)) and the activity of antioxidant enzymes (catalase and SOD) (by spectrophotometry) studied. Statistical processing of the results was carried out using the software package SPSS (version 10.0). Results of analysis show that defects associated with a lack of teeth do not affect the immune and oxidative balance of the oral cavity, but contribute to the development of destructive changes in the oral cavity's soft tissues, which manifested by an increase in the content of the proapoptotic protein P-53 in the saliva. After establishment of a denture, the intensity of apoptosis in the oral cavity tissues reduced. Establishment of a denture induced development of an inflammatory reaction during the first days, the intensity of which gradually decreased and completely disappeared at the end of the first month of the observation (manifested by the normalization of the parameters of the immune balance and antioxidant system). Minimal traumatic effects observed during establishment of a denture made based on Perflex Flexi Nylon.

Low-density lipoprotein docosahexaenoic acid nanoparticles induce ferroptotic cell death in hepatocellular carcinoma.

Low-density lipoprotein nanoparticles reconstituted with the natural omega-3 fatty acid, docosahexaenoic acid (LDL-DHA), have been reported to selectively kill hepatoma cells and reduce the growth of orthotopic liver tumors in the rat. To date, little is known about the cell death pathways by which LDL-DHA nanoparticles kill tumor cells. Here we show that the LDL-DHA nanoparticles are cytotoxic to both rat hepatoma and human hepatocellular carcinoma (HCC) cell lines. Following LDL-DHA treatment both rat and human HCC cells experience pronounced lipid peroxidation, depletion of glutathione and inactivation of the lipid antioxidant glutathione peroxidase-4 (GPX4) prior to cell death. Inhibitor studies revealed that the treated HCC cells die independent of apoptotic, necroptotic or autophagic pathways, but require the presence of cellular iron. These hallmark features are consistent and were later confirmed to reflect ferroptosis, a novel form of nonapoptotic iron-dependent cell death. In keeping with the mechanisms of ferroptosis cell death, GPX4 was also found to be a central regulator of LDL-DHA induced tumor cell killing. We also investigated the effects of LDL-DHA treatments in mice bearing human HCC tumor xenografts. Intratumoral injections of LDL-DHA severely inhibited the growth of HCC xenografts long term. Consistent with our in vitro findings, the LDL-DHA treated HCC tumors experienced ferroptotic cell death characterized by increased levels of tissue lipid hydroperoxides and suppression of GPX4 expression. CONCLUSION: LDL-DHA induces cell death in HCC cells through the ferroptosis pathway, this represents a novel molecular mechanism of anticancer activity for LDL-DHA nanoparticles.

Thymoquinone attenuates cyclophosphamide-induced pulmonary injury in rats.

OBJECTIVE: Antioxidant therapy may be useful in diseases with impaired oxidant-antioxidant balance. This study was designed to examine the effects of thymoquinone (TQ), an anti-inflammatory, antioxidant agent against cyclophosphamide (CP)-induced pulmonary oxidative damage. MATERIALS AND METHODS: Male Sprague-Dawley rats were categorized into four groups. Group I was control. Group II received TQ (100 mg/kg/day, p.o.) for 14 consecutive days. Group III was injected once with CP (150 mg/kg, i.p.). Group IV received TQ for 7 consecutive days, before and after CP injection. The parameters of study were tissue oxidant/antioxidant biomarkers and histological changes in rat lungs. RESULTS: A single intraperitoneal injection of CP markedly altered the levels of several biomarkers in lung homogenates. Significant increases in the content of lipid peroxides in lung were seen that paralleled the decreased levels of reduced glutathione. Cyclophosphamide increased the level of serum biomarkers: total protein, lactate dehydrogenase, and tumor necrosis factor-alpha (TNF-α). Treatment of rats with TQ 7 days before and after cyclophosphamide injection significantly attenuated the alterations in lung and serum biomarkers associated with inflammatory reactions, with less lipid peroxidation and restoration of antioxidants. Moreover, TQ attenuated the secretion of pro-inflammatory cytokine, TNF-α in rat serum. In addition, TQ effectively alleviated CP-induced histopathological changes in lung tissue. DISCUSSION AND CONCLUSION: Our results suggest that TQ produces a protective mechanism against CP-induced pulmonary damage and suggest a role of oxidative stress and inflammation in the pathogenesis.

Ethanol- and nicotine-induced membrane changes in embryonic and neonatal chick brains.

In order to study the effects of EtOH and/or nicotine on brain membrane fatty acid composition, various concentrations of EtOH and/or nicotine were injected into the air sac of chicken eggs at 0 days of incubation. Controls were injected with saline. Experimental groups were injected with either 200 micromol EtOH/kg egg, 100 micromol nicotine/kg egg, 200 micromol nicotine/kg egg, 200 micromol EtOH/kg and 100 micromol nicotine/kg egg, or 200 micromol EtOH/kg and 200 micromol nicotine/kg egg. In all experimental groups, EtOH- and nicotine-induced decreases in brain long-chain polyunsaturated membrane fatty acids were observed in stage 44 embryos, stage 45 embryos, and neonatal chicks. These EtOH- and nicotine-induced decreases in brain membrane polyunsaturated fatty acids correlated with elevated levels of brain lipid hydroperoxides and reduced brain acetylcholinesterase (AChE; EC. 3.1.1.7) activities.