An understanding of polychlorinated biphenyl (PCB) congener‐specific effects on cell membrane and intercellular communication is important within the studies of PCB absorption, organ‐related PCB ...accumulation and exertion of toxic responses. Toxic potential of PCBs is linked to various deleterious effects on human health, including neurotoxicity, immunotoxicity, reproductive toxicity and genotoxicity and, recently in 2016 International Agency for Research on Cancer (IARC) has upgraded the classification of PCBs to Group 1 “Carcinogenic to humans.” Proposed mechanisms of aforementioned PCBs adverse effects at cellular membrane level are: (i) downregulation of gap junction intercellular communication and/or connexins; (ii) compromised membrane integrity; and (iii) altered tight junction barrier function. This study, based on an extensive literature survey, shows the progress in scientific research of each of these three levels with the aim of pointing out the earliest toxic events of PCBs, which can result in serious cell/tissue/organ damage.
Polychlorinated biphenyl (PCB) effects are linked to neurotoxicity, immunotoxicity, reproductive toxicity, genotoxicity and carcinogenicity. Proposed PCB mechanisms of action at cellular membrane level are: (i) downregulation of gap junction intercellular communication and/or connexins; (ii) compromised membrane integrity; and (iii) altered tight junction barrier function. This study shows the progress in scientific research of each of these three levels with the aim of indicating the earliest toxic events, which can lead to serious cell/tissue/organ damage.
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•Essential and toxic elements in raw milk were measured from four regions of Croatia.•As, Cd and Pb were detected above LOD in only 2.3–18.2% of milk samples, Hg in none.•Significant ...differences in Al, Ba, Se and Zn content were found among the regions.•Risk assessment showed low exposure of all elements in milk except for Cd.
Concentrations of selected elements were measured in raw cow milk collected from four geographical regions in Croatia. The highest mean concentrations of Al, Ba, Fe and Zn were measured in milk from Central Croatia. Milk from the Croatian Littoral and Mountain region showed the highest mean content of Cd, Cr, Cu, Ni and Pb. The highest mean concentrations of As and Se were found in milk from Southern Croatia, while Mn had the highest values in Eastern Croatia. Mercury was not determined above the detection limit in any samples. Significant differences in the concentrations of Al, Ba, Se and Zn were found among the regions. A decrease in the Pb content was recorded compared to previous research in milk in Croatia. Estimation of the potential harmful effects of toxic and trace elements through milk consumption by comparing the established highest mean with toxicological limits showed low exposure with regard to Al, As, Ba, Cr, Cu, Hg, Fe, Ni, Se, Pb and Zn in adult populations in Croatia. The only exception was Cd concentrations in milk, which gave a higher contribution to toxicological limits, especially for consumers consuming greater quantities of milk per week.
Molekularni mehanizmi i morfološka obilježja autofagije Murati, Teuta; Drenški, Martina; Miletić, Marina ...
Hrvatski časopis za prehrambenu tehnologiju, biotehnologiju i nutricionizam,
12/2022, Volume:
17, Issue:
3-4
Journal Article
Open access
Autofagija je evolucijski dobro očuvan katabolički proces koji se događa u svim eukariotskim stanicama, a u kojem stanica razgradnjom oštećenih makromolekula i organela, između ostalog, osigurava ...hranjive tvari i energiju za održavanje vitalnih funkcija. Radi održavanja homeostaze, autofagija se na bazalnoj razini odvija neprestano u gotovo svim stanicama. Različiti fiziološki podražaji (oštećenja organela, nakupljanja proteinskih agregata, hipoksija, oksidacijski stres, upala i dr.) induciraju proces autofagije. Ipak, dokazano je da su nedostatak nutrijenata i energetski stres najsnažniji regulatori procesa autofagije. Pokretanjem autofagije stanice se „brane“ recikliranjem hranjivih sastojaka i/ili razgradnjom oštećenih organela. Uslijed prekomjerne eliminacije organela i citoplazmatskog sadržaja, prekomjerne mitofagije (selektivne razgradnje mitohondrija) i posljedičnog nedostatka energije, aktivacija autofagije može rezultirati i staničnom smrću (tzv. stanična smrt ovisna o autofagiji). Istraživanja su ukazala na važnost autofagije u očuvanju zdravlja kod bakterijskih i virusnih infekcija, karcinoma, neurodegenerativnih, metaboličkih i upalnih bolesti. Pojam autofagije najčešće se odnosi na najviše istražen oblik autofagije - makroautofagiju. Osim o tom obliku autofagije, u ovom preglednom radu dan je uvid u mehanizme i obilježja mikroautofagije i autofagije posredovane šaperonom (CMA).
Autophagy is an evolutionarily well-preserved catabolic process that occurs in all eukaryotic cells, in which the cell degrades damaged macromolecules and organelles to provide, among other things, nutrients and energy to maintain vital functions. To maintain homeostasis, autophagy occurs continuously at the basal level in almost all cells. Various physiological stimuli (organelle damage, accumulation of protein aggregates, hypoxia, oxidative stress, inflammation, etc.) trigger the autophagy process. However, nutrient deficiency and energy stress have been shown to be the strongest regulators of the autophagy process. By starting autophagy, cells “defend” themselves by recycling nutrients and/or degrading damaged organelles. Due to excessive removal of organelles and cytoplasmic content, excessive mitophagy (selective degradation of mitochondria), and consequent lack of energy, activation of autophagy can also lead to cell death (autophagy-dependent cell death). Research has shown the importance of autophagy in a variety of diseases, from bacterial and viral infections to cancer, neurodegenerative, metabolic and inflammatory diseases. The term autophagy usually refers to the most studied form of autophagy - macroautophagy. In addition to this form of autophagy, this review provides insight into the mechanisms and characteristics of microautophagy and chaperone-mediated autophagy (CMA).
Besides the use of resveratrol as a drug candidate, there are obstacles mainly due to its poor pharmacokinetic properties. Numerous studies are being conducted on the synthesis of resveratrol ...derivatives that exhibit enhanced biological activity. The aim of our research was to investigate activity of the newly synthesized ferrocene‐containing triacyl derivative of resveratrol to achieve cell protection from endo/exogenous ROS and reduction in cell death by assessing multiple endpoints. Our research showed that both resveratrol and the resveratrol derivatives (1–100 μM) lower the levels of ROS in CHO‐K1 cells. Resveratrol at doses <20 μM had little or no effect on cell proliferation, while at higher doses, a significant inhibitory effect on cell proliferation and viability has been noticed. The activity of the new derivative was significantly altered compared to resveratrol—cellular viability was not suppressed regardless of the concentration applied, and the extent of apoptosis was low. In summary, the new ferrocene‐resveratrol derivative has the potential to protect cells from oxidative stress due to its low cytotoxicity and retained antioxidant properties, whereas caution should be exercised with resveratrol at higher doses, as it significantly impairs cell viability and induces cell death. By linking ROS to specific diseases (relevance in neurodegenerative, cardiovascular, and neoplastic diseases), we can assume that the new resveratrol derivative can prevent or alleviate the mentioned disorders. Furthermore, recognition of the resveratrol derivative as an anti‐apoptotic chemical could be useful in the cultivation of various cell lines on a large scale in the industrial biotechnology.
The aim of our research was to investigate potential of resveratrol and the newly synthesized ferrocene‐containing triacyl derivative of resveratrol to achieve cell protection. Novel derivative protects cells from oxidative stress due to its low cytotoxicity and retained antioxidant properties, whereas caution should be exercised with resveratrol at higher doses. By linking ROS to specific diseases, we can assume that the resveratrol derivative can prevent/alleviate those conditions. Recognition of anti‐apoptotic properties of novel derivative can find application in industrial biotechnology.
Non-planar di-
-substituted PCB 153 (2,2’,4,4’,5,5’-hexachlorobiphenyl), one of the most abundant PCB congeners in the environment and in biological and human tissues, has been identified as ...potential endocrine disruptor affecting the reproductive and endocrine systems in rodents, wildlife, and humans. The aim of this study was to gain a deeper insight into its mode/mechanism of action in Chinese hamster ovary K1 cells (CHO-K1). PCB 153 (10–100 μmol/L) inhibited CHO-K1 cell proliferation, which was confirmed with four bioassays (Trypan Blue, Neutral Red, Kenacid Blue, and MTT), of which the MTT assay proved the most sensitive. PCB 153 also induced ROS formation in a dose-dependent manner. Apoptosis was seen after 6 h of exposure to PCB 153 doses ≥50 μmol/L, while prolonged exposure resulted in the activation of the necrotic pathway. PCB 153-induced disturbances in normal cell cycle progression were time-dependent, with the most significant effects occurring after 72 h.
Concentrations of selected trace elements Ag, Co and V in raw milk sampled from four geographical regions in Croatia were measured. Silver, Co and V were detected above the limit of detection within ...the range of 9.52%–30.8%, 1.6%–12.1% and 12.4%–30.8%. Silver concentrations were not detected in milk samples from the Croatian Littoral and Mountainous Croatia (CL-MC) region. Similar Ag content was found in Southern, Eastern and Central Croatia. The lowest mean of Co and V of 33.2 and 83.8 µg kg
−1
were found in the CL-MC region while the highest of 49.8 and 136.9 µg kg
−1
was found in Central Croatia. There were no statistically significant differences in Ag, Co and V contents between the four regions. The estimated daily dietary intakes (EDI) of total mean and total 95th percentile values of Ag, Co and V showed lower values in comparison with available EFSA health-based limits.
Pesticides and polychlorinated biphenyls (PCBs) are persistent environmental pollutants. When entering the food chain, they can represent a public health problem due to their negative effects on ...health. In this study, concentrations of organochlorine pesticides (OCPs), organophosphate pesticides (OPPs), pyrethroids, carbamates, and PCBs-a total 73 compounds-were determined in a total of 2268 samples of fat tissues (beef, pork, sheep, goat, poultry, game, horse, rabbit) and processed fat, meat, and processed meat products collected in Croatia during an 8-year period. In fatty tissues, 787 results exceeded the limits of quantification (LOQ): 16 OCPs, eight OPPs, six pyrethroids, one carbamate, and seven PCBs. The most positive results in fat samples were found for OCPs, with a frequency of quantification in the range of 57.5-87.5%. Hexachlorobenzene (HCB) and dichlorodiphenyldichloroethylene (DDE) were quantified in the highest percentages, in the ranges of 5.5-66.7% and 5.4-55.8%. Concentrations above the MRL values were determined for chlorpyrifos in pork fat and for resmethrin in six fat samples and one pâté. In 984 samples of meat and meat products, only 62 results exceeded the LOQ values. The highest frequency of quantification was determined for OCPs (25 samples), of which 40% were DDT isomers (60% DDE). Frequency quantifications of PCBs in fat samples were between 7.23 and 36.7%. An evaluation of the health risk assessment showed that the consumption of fat, meat, and meat products does not pose a threat to consumer health, since all EDI values were well below the respective toxicological reference values.
Polychlorinated biphenyls (PCBs) can induce chronic oxidative stress, inflammation, and cell death, leading to coronary heart disease, endothelial dysfunction, neurotoxicity, cancer, obesity, type 2 ...diabetes, reproductive dysfunction, etc. The aim of this study was to investigate possible protective effect of resveratrol (2.5–20 μM) in ovarian cells exposed to PCBs. An emphasis was on identifying mechanisms of resveratrol action upon distinct structure of the individual PCB congener—planar dioxin-like PCB 77 and non-planar di-
ortho
-substituted PCB 153. Multiple toxicity endpoint analysis was performed. Cell viability/proliferation was assessed by Trypan Blue exclusion method, Neutral Red, Kenacid Blue, and MTT bioassays. The level of oxidative stress was measured by fluorescent probes, and flow cytometry was applied to evaluate the mode of cell death. Resveratrol applied alone did not affect cell proliferation and viability in doses up to 20 µM, although significant antioxidative activity was observed. Toxic effects of
ortho
-PCB 153 (cytotoxicity, oxidative stress, and cell death) were mitigated by resveratrol. On the contrary pre-incubation with resveratrol did not result in cell viability protection when planar PCB 77 was applied. This indicates that resveratrol efficacy may be linked to specific structure of the individual congener, suggesting nutritional modulation of environmental insults caused by
ortho
-PCBs. We point out the importance of resveratrol dosage considering that synergistic cytotoxic effect with both PCB congeners is observed at concentrations ≥ 10 μM.
Graphical Abstract
The study examined the antioxidative physiological effects of phenolics from an ethanol-water extract of blackthorn flowers orally administrated to C57/BL6 mice for 28 days in daily doses of 25 mg of ...total phenolics/kg body weight. Contents of phenolics in the intestine, liver, and kidneys collected after 1, 7, 14, 21, and 28 days of extract administration were analyzed by UPLC-MS/MS method. In the same tissues, the antioxidative properties were determined as ferric reducing antioxidant power (FRAP), ABTS•+ scavenging activity, content of reduced glutathione (GSH), and activity of superoxide dismutase (SOD) and catalase (CAT). The lipid peroxidation in tissues was also evaluated by thiobarbituric acid reactive substances (TBARS) assay. The exposed mice (compared to the control ones) had a lower content of TBARS in all tissues mostly on the third/fourth week of daily consumption. SOD activity and GSH content increased on the 28th day in tissues. CAT activity was higher only in the liver after one week of consumption but remained unchanged in other organs throughout the experiment. Phenolic profiles were different in individual tissues. The most prominent increases compared to the control were determined for contents of 3- O -feruloylquinic acid, 4- O-p -coumaroylqiunic acid, kaempferol pentoside, and quercetin rhamnoside in the intestine; for ferulic acid and quercetin 3- O -rutinoside in the liver; and for quercetin 3- O -rutinoside, ferulic acid, and 4- O-p -coumaroylquinic acid in the kidneys. The screened phenolics with different distribution in tissues could be responsible for slight differences in the recorded antioxidative effects.
A novel synthetic approach toward a poorly explored bioorganometallic consisting of ferrocene-1,1'-diamine bearing structurally and chirally diverse amino acid sequences is reported. Until now, ...ferrocene-1,1'-diamine was suitable for accommodating only identical amino acid sequences at its N-termini, leading to the symmetrically disubstituted homochiral products stabilized through a 14-membered intramolecular hydrogen-bonded ring as is seen in antiparallel β-sheet peptides. The key step of the novel synthetic pathway is the transformation of Ac-Ala-NH-Fn-COOH (5) (Fn = 1,1'-ferrocenylene) to orthogonally protected Ac-Ala-NH-Fn-NHBoc (7). The spectroscopic analysis (IR, NMR, CD) of the novel compounds, corroborated with DFT studies, suggests the interesting feature of the ferrocene-1,1'-diamine scaffold. The same hydrogen-bonding pattern, i.e. a 14-membered hydrogen-bonded ring, was determined both in solution and in the solid state, thus making them promising, yet simple scaffolds capable of mimicking β-sheet peptides. In vitro screening of potential anticancer activity in Hep G2 human liver carcinoma cells and Hs 578 T human breast cancer cells revealed a cytotoxic pattern for novel compounds (150-500 μM) with significantly decreased cell proliferation.
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