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E-cigarettes induce toxicological effects that can raise the cancer risk. A frame from drug-metabolism and antioxidant homeostasis
E-CIGARETTES INDUCE TOXICOLOGICAL EFFECTS THAT CAN RAISE THE CANCER RISK. A FRAME
FROM DRUG-METABOLISM AND ANTIOXIDANT HOMEOSTASIS.
1)Canistro D. 2)Vivarelli F. 3)Cirillo S. 4)Cardenia V. 5)Rodriguez-estrada MT.
Dept of Pharmacy and Biotechnology, Unibo
Electronic cigarettes (e-cigs) are devices designed to deliver nicotine in a vaping solution 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. 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 occurrence.
In the present study, we investigated the co-mutagenic and cancer-initiating effects of e-cig vapour in a rat model. To explore whether e-cigs induce toxicological effects, such as those involving cytochrome P450 (CYP) changes, we analyzed the modulation of carcinogen metabolizingenzymes in the lung of rats exposed to e-cig vapour. We observed a significant increase in CYP1A1/2 (activating, for example, polychlorinated biphenyls, aromatic amines, dioxins and PAHs), CYP2B1/2 (activating olefins and halogenated hydrocarbons), 2C11 (activating nitrosamines and mycotoxins) and CYP3A (activating hexamethyl phosphoramide and nitrosamines) documented by the sharp rise in the corresponding probes.
Conversely, we observed that the antioxidant enzymes catalase, DT-diaphorase and glutathione peroxidase and the conjugating phase II glutathione S-transferases, mainly involved in xenobiotic detoxification, were noticeable decreased, whereas UDP-glucuronyl-transferase was substantially unchanged.
Extrapolated to humans, the corresponding boosted CYP-linked monooxygenases together with reduced activity of antioxidant and detoxifying machinery would predispose a subject to an enhanced cancer risk from the widely bioactivated e-cig vapour procarcinogens associated with an increased risk of lung cancer
Development of microparticles for oral administration of the non-conventional radical scavenger IAC and testing in an inflammatory rat model.
Development of microparticles for oral administration of the non-conventional radical scavenger
IAC and testing in an inflammatory rat model
1)Cirillo S.. 2)Paolini M.. 3)Vivarelli F.. 4)Passerini N.. 5)Albertini B.. 6)Di sabatino M. 7)Corace G.. 8)Luppi B..
9)Canistro D..
University of Bologna
The bis (1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)-decandioate (IAC) is an innovative nonconventional
radical scavenger used with success in several disease models, such as inflammation,
neurological disorders, hepatitis and diabetes. To date, the main limit for the drug use is
represented by the intraperitoneal (i.p.) route of administration used in the pharmacological
treatments. In order to develop a delivery system that allowed both oral administration and the
therapeutic efficacy, Solid Lipid Microparticles (SLMs) containing a theoretical 18% w/w of IAC
have been produced. Recently, three formulations (A, B, C) have been tested at different dosages
in an inflammation and pain rat model. Inflammatory model was induced by the use of an
intraplantar injection of 100ml/paw of Freund's complete adjuvant (FCA). Administered per os at
different dosages, IAC B (60% stearic acid-20% Compritol® HD5 ATO) was the most efficient
formulation in reducing oedema and alleviating pain, compared to the gold standard Paracetamol.
Since the anti-diabetic effects of the i.p. formulation of IAC was already demonstrated in vivo, we
are now investigating the therapeutic efficacy of the selected (B) oral IAC formulation (SLMs) in
streptozotocin-nicotinamide diabetic mice
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