Toxicological Aspects Associated with Consumption from Electronic Nicotine Delivery System (ENDS): Focus on Heavy Metals Exposure and Cancer Risk.

Tobacco smoking remains one of the leading causes of premature death worldwide. Electronic Nicotine Delivery Systems (ENDSs) are proposed as a tool for smoking cessation. In the last few years, a growing number of different types of ENDSs were launched onto the market. Despite the manufacturing differences, ENDSs can be classified as "liquid e-cigarettes" (e-cigs) equipped with an atomizer that vaporizes a liquid composed of vegetable glycerin (VG), polypropylene glycol (PG), and nicotine, with the possible addition of flavorings; otherwise, the "heated tobacco products" (HTPs) heat tobacco sticks through contact with an electronic heating metal element. The presence of some metals in the heating systems, as well as in solder joints, involves the possibility that heavy metal ions can move from these components to the liquid, or they can be adsorbed into the tobacco stick from the heating blade in the case of HTPs. Recent evidence has indicated the presence of heavy metals in the refill liquids and in the mainstream such as arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni), copper (Cu), and lead (Pb). The present review discusses the toxicological aspects associated with the exposition of heavy metals by consumption from ENDSs, focusing on metal carcinogenesis risk.

Effects of unburned tobacco smoke on inflammatory and oxidative mediators in the rat prefrontal cortex.

Although the Food and Drug Administration has authorized the marketing of "heat-not-burn" (HnB) electronic cigarettes as a modified risk tobacco product (MRTP), toxicological effects of HnB smoke exposure on the brain are still unexplored. Here, paramagnetic resonance of the prefrontal cortex (PFC) of HnB-exposed rats shows a dramatic increase in reactive radical species (RRS) yield coupled with an inflammatory response mediated by NF-κB-target genes including TNF-α, IL-1ß, and IL-6 and the downregulation of peroxisome proliferator-activated receptor (PPAR) alpha and gamma expression. The PFC shows higher levels of 8-hydroxyguanosine, a marker of DNA oxidative damage, along with the activation of antioxidant machinery and DNA repair systems, including xeroderma pigmentosum group C (XPC) protein complex and 8-oxoguanine DNA glycosylase 1. HnB also induces the expression of drug-metabolizing enzymes such as CYP1A1, CYP2A6, CYP2B6, and CYP2E, particularly involved in the biotransformation of nicotine and several carcinogenic agents such as aldehydes and polycyclic aromatic hydrocarbons here recorded in the HnB stick smoke. Taken together, these effects, from disruption of redox homeostasis, inflammation, PPAR manipulation along with enhanced bioactivation of neurotoxicants, and upregulation of cMYC protooncogene to impairment of primary cellular defense mechanisms, suggest a possible increased risk of brain cancer. Although the HnB device reduces the emission of tobacco toxicants, our findings indicate that its consumption may carry a risk of potential adverse health effects, especially in non-smokers so far. Further studies are needed to fully understand the long-term effects of these devices.

Potential Harm of IQOS Smoke to Rat Liver.

The Food and Drug Administration has recently classified the IQOS electronic cigarette as a modified-risk tobacco product. However, IQOS cigarettes still release various harmful constituents typical of conventional cigarettes (CCs), although the concentrations are markedly lower. Here, we investigated the damaging effects of IQOS smoking on the liver. Male Sprague Dawley rats were exposed, whole body, 5 days/week for 4 weeks to IQOS smoke (4 sticks/day), and hepatic xenobiotic metabolism, redox homeostasis and lipidomic profile were investigated. IQOS boosted reactive radicals and generated oxidative stress. Exposure decreased cellular reserves of total glutathione (GSH) but not GSH-dependent antioxidant enzymes. Catalase and xanthine oxidase were greater in the exposed group, as were various hepatic CYP-dependent monooxygenases (CYP2B1/2, CYP1A1, CYP2A1, CYP2E1-linked). Respiratory chain activity was unaltered, while the number of liver mitochondria was increased. IQOS exposure had an impact on the hepatic lipid profile. With regard to the expression of some MAP kinases commonly activated by CC smoking, IQOS increased the p-p38/p38 ratio, while erythroid nuclear transcription factor 2 (Nrf2) was negatively affected. Our data suggest that IQOS significantly impairs liver function, supporting the precautionary stance taken by the WHO toward the use of these devices, especially by young people and pregnant women.

Effects of Different Opioid Drugs on Oxidative Status and Proteasome Activity in SH-SY5Y Cells.

Opioids are the most effective drugs used for the management of moderate to severe pain; however, their chronic use is often associated with numerous adverse effects. Some results indicate the involvement of oxidative stress as well as of proteasome function in the development of some opioid-related side effects including analgesic tolerance, opioid-induced hyperalgesia (OIH) and dependence. Based on the evidence, this study investigated the impact of morphine, buprenorphine or tapentadol on intracellular reactive oxygen species levels (ROS), superoxide dismutase activity/gene expression, as well as ß2 and ß5 subunit proteasome activity/biosynthesis in SH-SY5Y cells. Results showed that tested opioids differently altered ROS production and SOD activity/biosynthesis. Indeed, the increase in ROS production and the reduction in SOD function elicited by morphine were not shared by the other opioids. Moreover, tested drugs produced distinct changes in ß2(trypsin-like) and ß5(chymotrypsin-like) proteasome activity and biosynthesis. In fact, while prolonged morphine exposure significantly increased the proteolytic activity of both subunits and ß5 mRNA levels, buprenorphine and tapentadol either reduced or did not alter these parameters. These results, showing different actions of the selected opioid drugs on the investigated parameters, suggest that a low µ receptor intrinsic efficacy could be related to a smaller oxidative stress and proteasome activation and could be useful to shed more light on the role of the investigated cellular processes in the occurrence of these opioid drug side effects.

On the toxicity of e-cigarettes consumption: Focus on pathological cellular mechanisms.

Tobacco smoking remains without a doubt one of the leading causes of premature death worldwide. In combination with conventional protocols for smoking cessation, e-cigarettes have been proposed as a useful tool to quit smoking. Advertised as almost free of toxic effects, e-cigarettes have rapidly increased their popularity, becoming a sought-after device, especially among young people. Recently some health concerns about e-cigarette consumption are being raised. It is well known that they can release several toxic compounds, some of which are carcinogenic to humans, and emerging results are now outlining the risks related to the onset of respiratory and cardiovascular diseases and even cancer. The present review shows the emerging evidence about the role of technical components of the devices, the e-liquid composition as well as customization by consumers. The primary topics we discuss are the main toxicological aspects associated with e-cigarette consumption, focusing on the molecular pathways involved. Here it will be shown how exposure to e-cigarette aerosol induces stress/mitochondrial toxicity, DNA breaks/fragmentation following the same pathological pathways triggered by tobacco smoke, including the deregulation of molecular signalling axis associated with cancer progression and cell migration. Risk to fertility and pregnancy, as well as cardiovascular risk associated with e-cigarette use, have also been reported.

Anticancer potential of allicin: A review.

Phytochemicals have attracted attention in the oncological field because they are biologically friendly and have relevant pharmacological activities. Thanks to the intense and unique spicy aroma, garlic is one of the most used plants for cooking. Its consumption is correlated to health beneficial effects towards several chronic diseases, such as cancer, mainly attributable to allicin, a bioactive sulfur compound stored in different plant parts in a precursor form. The objective of this review is to present and critically discuss the chemistry and biosynthesis of allicin, its pharmacokinetic profile, its anticancer mechanisms and molecular targets, and its selectivity towards tumor cells. The research carried out so far revealed that allicin suppresses the growth of different types of tumors. In particular, it targets many signaling pathways associated with cancer development. Future research directions are also outlined to further characterize this promising natural product.

Unburned Tobacco Cigarette Smoke Alters Rat Ultrastructural Lung Airways and DNA.

INTRODUCTION: Recently, the Food and Drug Administration authorized the marketing of IQOS Tobacco Heating System as a Modified Risk Tobacco Product based on an electronic heat-not-burn technology that purports to reduce the risk. METHODS: Sprague-Dawley rats were exposed in a whole-body mode to IQOS aerosol for 4 weeks. We performed the chemical characterization of IQOS mainstream and we studied the ultrastructural changes in trachea and lung parenchyma of rats exposed to IQOS stick mainstream and tissue pro-inflammatory markers. We investigated the reactive oxygen species amount along with the markers of tissue and DNA oxidative damage. Moreover, we tested the putative genotoxicity of IQOS mainstream through Ames and alkaline Comet mutagenicity assays. RESULTS: Here, we identified irritating and carcinogenic compounds including aldehydes and polycyclic aromatic hydrocarbons in the IQOS mainstream as sign of incomplete combustion and degradation of tobacco, that lead to severe remodelling of smaller and largest rat airways. We demonstrated that IQOS mainstream induces lung enzymes that activate carcinogens, increases tissue reactive radical concentration; promotes oxidative DNA breaks and gene level DNA damage; and stimulates mitogen activated protein kinase pathway which is involved in the conventional tobacco smoke-induced cancer progression. CONCLUSIONS: Collectively, our findings reveal that IQOS causes grave lung damage and promotes factors that increase cancer risk. IMPLICATIONS: IQOS has been proposed as a safer alternative to conventional cigarettes, due to depressed concentration of various harmful constituents typical of traditional tobacco smoke. However, its lower health risks to consumers have yet to be determined. Our findings confirm that IQOS mainstream contains pyrolysis and thermogenic degradation by-products, the same harmful constituents of traditional cigarette smoke, and, for the first time, we show that it causes grave lung damage and promotes factors that increase cancer risk in the animal model.

Castanea sativa Mill. bark extract cardiovascular effects in a rat model of high-fat diet.

Ellagitannins may have a beneficial impact in cardiovascular diseases. The aim of the study was to evaluate the effect of high-fat diet (HFD) and the efficacy of Castanea sativa Mill. bark extract (ENC) on cardiac and vascular parameters. Rats were fed with regular diet, (RD, n = 15), HFD (n = 15), RD + ENC (20 mg/kg/day by gavage, n = 15), and HFD + ENC (same dose, n = 15) and the effects on body weight, biochemical serum parameters, and inflammatory cytokines determined. Cardiac functional parameters and aorta contractility were also assessed on isolated atria and aorta. Results showed that ENC reduced weight gain and serum lipids induced by HFD. In in vitro assays, HFD decreased the contraction force of left atrium, increased right atrium chronotropy, and decreased aorta K+ -induced contraction; ENC induced transient positive inotropic and negative chronotropic effects on isolated atria from RD and HFD rats and a spasmolytic effect on aorta. In ex vivo experiments, ENC reverted inotropic and chronotropic changes induced by HFD and enhanced Nifedipine effect more on aorta than on heart. In conclusion, ENC restores metabolic dysfunction and cardiac cholinergic muscarinic receptor function, and exerts spasmolytic effect on aorta in HFD rats, highlighting its potential as nutraceutical tool in obesity.

Impact of electronic cigarette heating coil resistance on the production of reactive carbonyls, reactive oxygen species and induction of cytotoxicity in human lung cancer cells in vitro.

Electronic cigarette (e-cigarette; e-cig) use has grown exponentially in recent years despite their unknown health effects. E-cig aerosols are now known to contain hazardous chemical compounds, including carbonyls and reactive oxygen species (ROS), and these compounds are directly inhaled by consumers during e-cig use. Both carbonyls and ROS are formed when the liquid comes into contact with a heating element that is housed within an e-cig's atomizer. In the present study, the effect of coil resistance (1.5â€¯Ω and 0.25â€¯Ω coils, to obtain a total wattage of 8 ±â€¯2 W and 40 ±â€¯5 W, respectively) on the generation of carbonyls (formaldehyde, acetaldehyde, acrolein) and ROS was investigated. The effect of the aerosols generated by different coils on the viability of H1299 human lung carcinoma cells was also evaluated. Our results show a significant (p < 0.05) correlation between the low resistance coils and the generation of higher concentrations of the selected carbonyls and ROS in e-cig aerosols. Moreover, exposure to e-cig vapor reduced the viability of H1299 cells by up to 45.8%, and this effect was inversely related to coil resistance. Although further studies are needed to better elucidate the potential toxicity of e-cig emissions, our results suggest that these devices may expose users to hazardous compounds which, in turn, may promote chronic respiratory diseases.

The Customizable E-cigarette Resistance Influences Toxicological Outcomes: Lung Degeneration, Inflammation, and Oxidative Stress-Induced in a Rat Model.

Despite the knowledge gap regarding the risk-benefit ratio of the electronic cigarette (e-cig), its use has grown exponentially, even in teenagers. E-cig vapor contains carcinogenic compounds (eg, formaldehyde, acetaldehyde, and acrolein) and free radicals, especially reactive oxygen species (ROS) that cause toxicological effects, including DNA damage. The role of e-cig voltage customization on molecule generation has been reported, but the effects of the resistance on e-cig emissions and toxicity are unknown. Here, we show that the manipulation of e-cig resistance influences the carbonyls production from nonnicotine vapor and the oxidative and inflammatory status in a rat model. Fixing the voltage at the conventional 3.5 V, we observed that the amount of the selected aldehydes increased as the resistance decreased from 1.5 to 0.25 Ω. Under these conditions, we exposed Sprague Dawley rats to e-cig aerosol for 28 days, and we studied the pulmonary inflammation, oxidative stress, tissue damage, and blood homeostasis. We found a perturbation of the antioxidant and phase II enzymes, probably related to the increased ROS levels due to the enhanced xanthine oxidase and P450-linked monooxygenases. Furthermore, frames from scanning electron microscope showed a disorganization of alveolar and bronchial epithelium in 0.25 Ω group. Overall, various toxicological outcomes, widely recognized as smoke-related injuries, can potentially occur in e-cig consumers who use low-voltage and resistance device. Our study suggests that certain "tips for vaping safety" cannot be established, and encourages further independent investigations to help public health agencies in regulating the e-cig use.

Co-carcinogenic effects of vitamin E in prostate.

A large number of basic researches and observational studies suggested the cancer preventive activity of vitamin E, but large-scale human intervention trials have yielded disappointing results and actually showed a higher incidence of prostate cancer although the mechanisms underlying the increased risk remain largely unknown. Here we show through in vitro and in vivo studies that vitamin E produces a marked inductive effect on carcinogen-bioactivating enzymes and a pro-oxidant status promoting both DNA damage and cell transformation frequency. First, we found that vitamin E in the human prostate epithelial RWPE-1 cell line has the remarkable ability to upregulate the expression of various phase-I activating cytochrome P450 (CYP) enzymes, including activators of polycyclic aromatic hydrocarbons (PAHs), giving rise to supraphysiological levels of reactive oxygen species. Furthermore, our rat model confirmed that vitamin E in the prostate has a powerful booster effect on CYP enzymes associated with the generation of oxidative stress, thereby favoring lipid-derived electrophile spread that covalently modifies proteins. We show that vitamin E not only causes DNA damage but also promotes cell transformation frequency induced by the PAH-prototype benzo[a]pyrene. Our findings might explain why dietary supplementation with vitamin E increases the prostate cancer risk among healthy men.

Impairment of testicular function in electronic cigarette (e-cig, e-cigs) exposed rats under low-voltage and nicotine-free conditions.

Despite the lack of knowledge of the effects of electronic cigarettes (e-cigarettes, e-cigs) on public health, they have been proposed as a part of smoking cessation efforts. Recently, several basic scientific studies have pointed out how e-cigs can generate carcinogens, such as e-cig liquid thermal degradation by-products, and how the exposure can lead to genomic damage through inhibiting DNA repair or disrupting the redox homeostasis. However, scientific studies have pointed out how e-cigs can generate carcinogens and their release could be avoided setting the device to a low-voltage regimen. To test this feasibility, we show the effects of e-cig vapour generated from a low-voltage device filled with a nicotine-free liquid on rat testicular functions. The chemical analysis revealed the presence of carbonyls, such as formaldehyde, acetaldehyde and acrolein. Rats exposed reported a lower relative testis weight and higher levels of lactate dehydrogenase (LDH) as tissue damage marker, along with an impairment of 3ß-hydroxysteroid dehydrogenase (3ß-HSD), 17ß-hydroxysteroid dehydrogenase (17ß-HSD) and glucose-6-phosphate dehydrogenase (G6PDH) as key enzymes in the steroidogenesis pathway. The pro-oxidative environment was confirmed by the higher amount of reactive oxygen species (ROS), the development of lipid peroxidation and protein carbonylation, as well as from the disruption of antioxidant capability. Finally, we observed a higher rate of DNA unwinding in white blood cell line and boosted lipoxygenase (LOX)-linked activity, a tumour promotion marker. Even with the device setting at weak conditions, our results if extrapolated to humans suggest that exposure to e-cig vapours might alter gonads function in male vapers.

Liver and intestinal protective effects of Castanea sativa Mill. bark extract in high-fat diet rats.

The effects of Castanea sativa Mill. have been studied in high fat diet (HFD) overweight rats. Natural Extract of Chestnut bark (Castanea sativa Mill.) (ENC®), rich in ellagitannins, has been studied in 120 male Sprague-Dawley rats, divided in four groups. Two groups were controls: regular (RD) and HDF diet. Two groups received ENC® (20 mg/kg/day): RD + ENC® and HFD + ENC®. At baseline and at 7, 14 and 21 days, weight gain, serum lipids, plasma cytokines, liver histology, microsomial enzymes and oxidation, intestinal oxidative stress and contractility were studied. HFD increased body weight, increased pro-inflammatory cytokines, induced hepatocytes microvescicular steatosis, altered microsomial, increased liver and intestinal oxidative stress, deranged intestinal contractility. In HFD-fed rats, ENC® exerted antiadipose and antioxidative activities and normalized intestinal contractility, suggesting a potential approach to overweight management associated diseases.

The effect of electronic-cigarettes aerosol on rat brain lipid profile.

The electronic cigarettes (e-cigarettes, e-cigs) have become the most sought-after alternative to the traditional cigarettes, partly due to the widespread perception of safety. However, the high temperature reached by e-cig solutions can generate toxic compounds, some of which are listed as known human carcinogens. To evaluate the impact of e-cig aerosol on rat brain lipid profile, twenty male Sprague Dawley rats were exposed to 11 cycles/day (E-cig group), to consume 1 mL/day of e-liquid, for 5 days/week up to 8 weeks. Ten rats were sacrificed after 4 weeks (4w) and ten at the end of treatment (8w). The composition of total fatty acids, sterols and oxysterols of the lipid fraction of rat brains, was analyzed. The results of the E-cig group were compared with those of the control group (not exposed). After 8 weeks, the saturated fatty acids significantly raised up to 7.35 mg/g tissue, whereas polyunsaturated fatty acids decreased reaching 3.17 mg/g. The e-cig vaping increased both palmitic (3.43 mg/g) and stearic acids (3.82 mg/g), while a significant decrement of arachidonic (1.32 mg/g) and docosahexaenoic acids (1.00 mg/g) was found. Atherogenic (0.5) and thrombogenic (1.12) indices also increased in 8w treated animals. The e-cig aerosol significantly impacted the cholesterol homeostasis, since the latter at 8w (21.57 mg/g) was significantly lower than control (24.56 mg/g); moreover, a significant increase of 7-dehydrocholesterol (1.87 mg/g) was also denoted in e-cig group. The e-cig aerosol also reduced the oxysterol formation (19.55 µg/g) after 4 weeks of exposure, except for triol and 5α,6α-epoxycholesterol (α-EC). The principal component analysis (PCA) separated all E-cig from control groups, evidencing that oxysterols (except triol and 24(S)-hydroxycholesterol (24(S)-HC)) were inversely correlated to 7-DHC and TI. The present research revealed that e-cigs aerosol affected the lipid and cholesterol homeostasis in rat brain, which could contribute to the new occurrence of some neurodegenerative diseases.

Geraniol Pharmacokinetics, Bioavailability and Its Multiple Effects on the Liver Antioxidant and Xenobiotic-Metabolizing Enzymes.

Geraniol is a natural monoterpene showing anti-inflammatory, antioxidant, neuroprotective and anticancer effects. No pharmacokinetic and bioavailability data on geraniol are currently available. We therefore performed a systematic study to identify the permeation properties of geraniol across intestinal cells, and its pharmacokinetics and bioavailability after intravenous and oral administration to rats. In addition, we systematically investigated the potential hepatotoxic effects of high doses of geraniol on hepatic phase I, phase II and antioxidant enzymatic activities and undertook a hematochemical analysis on mice. Permeation studies performed via HPLC evidenced geraniol permeability coefficients across an in vitro model of the human intestinal wall for apical to basolateral and basolateral to apical transport of 13.10 ± 2.3 × 10-3 and 2.1 ± 0.1â‹…× 10-3 cm/min, respectively. After intravenous administration of geraniol to rats (50 mg/kg), its concentration in whole blood (detected via HPLC) decreased following an apparent pseudo-first order kinetics with a half-life of 12.5 ± 1.5 min. The absolute bioavailability values of oral formulations (50 mg/kg) of emulsified geraniol or fiber-adsorbed geraniol were 92 and 16%, respectively. Following emulsified oral administration, geraniol amounts in the cerebrospinal fluid of rats ranged between 0.72 ± 0.08 µg/mL and 2.6 ± 0.2 µg/mL within 60 min. Mice treated with 120 mg/kg of geraniol for 4 weeks showed increased anti-oxidative defenses with no signs of liver toxicity. CYP450 enzyme activities appeared only slightly affected by the high dosage of geraniol.

The combined effect of Sango sprout juice and caloric restriction on metabolic disorders and gut microbiota composition in an obesity model.

The main purpose of this study was to compare the benefits of SSJ supplementation in obese rats with those achieved only by switching the alimentary regimen from high-fat (HFD) to the regular one (RD) in liver, ileum and prostate. Furthermore, changings in caecal chime microbiota were investigated. SSJ was administered to rats in combination with a RD (HFD-RD + SSJ). The switch from HFD to RD led to a weight loss of almost 9.8 g, and the total cholesterol was found to be significantly lower. In the HFD-RD + SSJ group, all values were improved compared with the HFD control, and the weight decrement was higher (-23.29 g) with respect to HFD-RD. HFD led to a widespread increment of oxidative stress (OS) markers in liver, ileum and prostate. SSJ has shown to improve the results achieved by the suspension of HFD and it has proven effective wherever the only switch in diet regimen failed.

E-cigarettes induce toxicological effects that can raise the cancer risk.

Electronic cigarettes (e-cigs) are devices designed to deliver nicotine in a vaping solution rather than smoke and without tobacco combustion. Perceived as a safer alternative to conventional cigarettes, e-cigs are aggressively marketed as lifestyle-choice consumables, thanks to few restrictions and a lack of regulatory guidelines. E-cigs have also gained popularity among never-smokers and teenagers, becoming an emergent public health issue. Despite the burgeoning worldwide consumption of e-cigs, their safety remains largely unproven and it is unknown whether these devices cause in vivo toxicological effects that could contribute to cancer. Here we demonstrate the co-mutagenic and cancer-initiating effects of e-cig vapour in a rat lung model. We found that e-cigs have a powerful booster effect on phase-I carcinogen-bioactivating enzymes, including activators of polycyclic aromatic hydrocarbons (PAHs), and increase oxygen free radical production and DNA oxidation to 8-hydroxy-2'-deoxyguanosine. Furthermore, we found that e-cigs damage DNA not only at chromosomal level in peripheral blood, such as strand breaks in leucocytes and micronuclei formation in reticulocytes, but also at gene level such as point mutations in urine. Our results demonstrate that exposure to e-cigs could endanger human health, particularly among younger more vulnerable consumers.

Dietary effects of Raphanus sativus cv Sango on lipid and oxysterols accumulation in rat brain: A lipidomic study on a non-genetic obesity model.

The present study aimed to evaluate the impact of Raphanus sativus cv Sango sprout juice (SSJ) administration (75mg/kg b.w. SSJ/day) on the brain lipidomic profile (fatty acid, sterols, cholesterol oxidation) of rats (non-genetic model) subjected to a high-fat (34% crude fat) dietary regimen. The SSJ did not affect the lipid infiltration (7.7-9.3%) and the fatty acid composition of the rat brain, which was mainly composed by unsaturated fatty acids (∼58%); however, the high-fat diet regimen significantly halved linoleic acid (LA). The high-fat diet also decreased (21.13mg/g) the level of brain cholesterol with respect to the regular diet (4.5% crude fat) (23.83mg/g); however, when the diet was shifted from high-fat to a regular regimen with or without SSJ supplementation, the levels of cholesterol significantly (p <0.05) increased up to 30.46mg/g of brain. The main oxysterols were 24(S)-hydroxycholesterol (24(S)-HC) and ß-epoxycholesterol (ß-EC). The high-fat diet led to the highest cholesterol oxidation (63.1µg/g), increasing 27-hydroxycholesterol (27-HC) infiltration (0.24µg/g rat brain) through the blood-brain barrier (BBB) compared to the regular diet (0.13µg/g rat brain). On the other hand, when the diet was switched from high-fat to a regular regimen with SSJ supplementation, a significant reduction of 27-HC in the rat brain was found. Although 24-HC did not significantly change (p=0.054), an increasing trend was observed when high-fat diet was supplied. The principal component analysis (PCA) revealed that SSJ was more active in counteracting cholesterol oxidation when supplied with the high-fat diet, due to inverse correlation with 24(S)-HC and 27-HC; however, further studies are needed to better understand which is the relationship between LA and cholesterol homeostasis in rat brain.

Aspartame, a bittersweet pill.

For the first time, the aspartame case shows how a corporation decided to ban an artificial ingredient in the wake of public opinion notwithstanding the regulatory assurance claims that it is safe. PepsiCo Inc. made an unprecedented decision most likely based on life-span carcinogenicity bioassay studies from the Cesare Maltoni Cancer Research Center of the Ramazzini Institute (CMCRC/RI), which provide consistent evidence of aspartame's carcinogenicity in rodents. Although CMCRC/RI experiments have been criticized for not complying with Organisation for Economic Co-operation and Development (OECD) guidelines, the newly launched aspartame-free soft drink may not be an isolated case. In the light of vinyl chloride-, formaldehyde- or benzene-associated carcinogenicity discovered for the first time by CMCRC/RI in the same way, it seems the guidelines need to be re-evaluated to avoid the credibility of international regulatory agencies being compromised by consumer opinion.

Comparison between in toto peach (Prunus persica L. Batsch) supplementation and its polyphenolic extract on rat liver xenobiotic metabolizing enzymes.

Over the past years, there has been a growing interest in the natural constituents of foods as a potential means of cancer control. To date, epidemiology studies seem to indicate an inverse association between regular consumption of fruit and vegetables and cancer risk. Here, the potential chemopreventive activity of the polyphenolic extract (PPE) of peach (Prunus persica L. Batsch) and of the freeze-dried fruit in toto (LFT), focusing on the modulation of xenobiotic metabolizing enzymes (XMEs) in vivo, was investigated. Rats were daily supplemented with LFT at 250 and 500 mg/kg b.w. or with the corresponding amount of PPE (2.5 and 5 mL/kg b.w., respectively) for either 7 or 14 days. While PPE treatment resulted in a widespread phase-I inactivation, a complex modulation pattern with drastic decreases (7α-testosterone hydroxylase, pentoxyresorufin O-dealkylase (PROD)), coupled with marked up-regulations of ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-demethylase (MROD) after LFT administration, was seen. A notable down-regulation (over 50%) following LFT or PPE treatment for the phase-II enzymes was also recorded. The observed remarkable changes in XMEs, if reproduced in humans, might have public health implications. These data suggest caution in promoting peach fruit (mono-diet) consumption or its polyphenolic extract in the field of chemoprevention.