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The digestibility (in vitro), toxicity and metabolic effects of rapeseed (RPH) and sunflower (SPH) protein hydrolysates have been evaluated in a murine animal model. The enzyme AlcalaseVR was employed to obtain a mild enzymatic hydrolysis of rapeseed and sunflower defatted seed meals (DSM) protein isolates. Both hydrolysates showed higher in vitro digestibility than the respective DSM, presumably as a consequence of the hydrolysis process that they had undergone. In vivo, RPH and SPH were well tolerated. Body and organ weights, biochemical blood parameters from treated male mice were comparable to controls. Food intake was regular in RPH and SPH animals, suggesting a good palatability of the hydrolysates. Not relevant perturbations of the principal hepatic and renal drug metabolism enzymes were observed in RPH or SPH mice. In conclusion, protein hydrolysates from sunflower and rapeseed DSM did not determine relevant toxicological effects; therefore, they could be considered as alternative protein sources and/or food ingredients.

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.

Purpose: We previously showed the positive effects of the new antioxidant molecule bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)-decandioate (IAC) in reducing basal hyperglycaemia and relieving glucose intolerance in a diabetes model. However, the chemical properties of IAC did not allow an efficient oral administration, thus representing the main failing of that study. Here, we tested the effect of a new oral delivery system based on solid lipid microparticles (SLMs) in a diabetes mouse model. Methods: The diabetes model was induced in C57B1/6J mice using streptozotocin and nicotinamide. Only the animals that overcame the glycaemic threshold of 180 mg/dL were enrolled in the study. Diabetic animals were then randomly assigned to 4 groups (n = 9) and treated once a day for 5 consecutive weeks with IAC (50, 100, and 150 mg/kg b.w.). The control group was composed of (n = 7) healthy mice that received only the vehicle. Glucose level was weekly monitored during the treatment period and up to 3 weeks after the suspension of the treatment. Glucose tolerance and insulin-resistance test were carried out. Results: Our results showed that SLMs maintained the IAC effect in reducing basal hyperglycaemia as well as improving the insulin sensitivity and glucose tolerance. Conclusion: The present study confirms that SLMs are promising drug carriers, which allow the oral administration of IAC ensuring its therapeutic efficacy. The concrete possibility to administer IAC per os represents a significant breakthrough in the putative consideration of this multi-radical scavenger in the diabetes therapeutic approach.

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.

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 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase (17β-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.

Aims A large meta-analysis of randomized clinical trials has seriously questioned chemoprevention based on vitamins including vitamin E (VE), and an increased risk for cancer among long-term users was actually seen. However, the mechanism underlying these findings still remain unknown. To clarify the mechanism, in an in vivo model we studied the putative disruption of redox homeostasis and the perturbation of carcinogen metabolizing enzymes determined by VE. Main methods Male Sprague–Dawley rats were treated ip with either 100 or 200 mg/kg b.w. daily for 7 or 14 consecutive days. Controls received vehicle only. Cytochrome P450 (CYP) content, CYP-reductase, CYP-linked monooxygenases, as well as phase-II and the antioxidant enzymes catalase and NAD(P)H:quinone reductase were investigated in both liver and kidney. Free radical species in tissue subcellular preparations were measured by electronic paramagnetic resonance (EPR) spectroscopy coupled to a radical probe technique. Key findings No substantial changes of hepatic xenobiotic metabolism enzymes were determined by VE. Conversely, a powerful booster effect of various renal phase-I carcinogen bioactivating enzymes at both dosages and observational times was recorded. While no relevant changes of post-oxidative phase-II reactions were found in the liver, a significant inactivating effect was caused by VE in renal tissues. Antioxidant enzymes were found mainly downregulated by the treatment. In the kidney, a marked free radical over-generation linked to CYP induction was observed. Significance This study proved that VE acts as a co-carcinogen and pro-oxidant agent. Such epigenetic mechanisms may contribute to explain the harmful outcomes observed in humans.

Sanitation is of crucial importance for the microbiological safety of drinking water. However, chlorination of water rich in organic material produces disinfection by-products (DBPs), many of which have been reported to be mutagenic and/or carcinogenic compounds such as haloacetic acids and trihalomethanes. Epidemiological studies have suggested a link between drinking water consumption and cancer. We previously observed that Cyprinus carpio fish exposed to DBPs, may be subject to epigenetic effects such as those referable to the up-regulation of cytochrome P450 (CYP) superfamily (ex. co-mutagenesis/co-carcinogenesis and oxidative stress) that has been associated to non-genotoxic carcinogenesis. Our goal was to study the xenobiotic metabolism in mollusks exposed in situ to surface water of Lake Trasimene (Central Italy) treated with several disinfectants such as the traditional chlorine dioxide (ClO2), sodium hypochlorite (NaClO) or the relatively new one peracetic acid (PAA). The freshwater bivalves (Dreissena polymorpha) being selected as biomarker, have the unique ability to accumulate pollutants. Freshwater bivalves were maintained in surface water containing each disinfectant individually (1-2 mg/L). Following an exposure period up to 20 days during the fall period, microsomes were collected from the mussels, then tested for various monooxygenases. Strong CYP inductions were observed. These data indicate that drinking water disinfection generates harmful DBP mixtures capable of determining a marked perturbation of CYP-supported reactions. This phenomenon, being associated to an increased pro-carcinogen bioactivation and persistent oxidative stress, could provide an explanation for the observational studies connecting the regular consumption of drinking water to increased risk of various cancers in humans.

BACKGROUND: Obesity is recognized as a leading global health problem, correlated with an increased risk for several chronic diseases. One strategy for weight control management includes the use of vegetables rich in bioactive compounds to counteract weight gain, improve the antioxidant status and stimulate lipid catabolism. AIM OF THE STUDY: The aim of this study was to investigate the role of Raphanus sativus Sango sprout juice (SSJ), a Brassica extraordinarily rich in anthocyanins (AC) and isothiocyanates (ITCs), in a non-genetic model of obesity (high fat diet-HFD induced). METHODS: Control groups were fed with HFD or regular diet (RD). After a 10-week period, animals were assigned to experimental units and treated by gavage for 28 days as follows: HFD and RD control groups (rats fed HFD or RD and treated with vehicle only) and HFD-treated groups (rats fed HFD and treated with 15, 75 or 150 mg/kg b.w. of SSJ). Body weight and food consumption were recorded and serum lipid profile was measured (total cholesterol, triglycerides, and non-esterified fatty acids). Hepatic phase-I, phase-II as well as antioxidant enzymatic activities were assessed. RESULTS: SSJ lowered total cholesterol level, food intake and liver weight compared with HFD rodents. SSJ at medium dose proved effective in reducing body-weight (~19 g reduction). SSJ was effective in up-regulating the antioxidant enzymes catalase, NAD(P)H: quinone reductase, oxidised glutathione reductase and superoxide dismutase, which reached or exceeded RD levels, as well as the phase II metabolic enzyme UDP-glucuronosyl transferase (up to about 43%). HFD up-regulated almost every cytochrome P450 isoform tested, and a mild down-regulation to baseline was observed after SSJ intervention. CONCLUSION: This work reveals, for the first time, the antioxidant, hypolipidemic and antiobesity potential of SSJ, suggesting its use as an efficient new functional food/nutraceutical product.

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.