ABSTRACT
Title
Drug metabolism modulation-based anticancer strategy: “organic” vs “integrated” apple mono-diet.
Authors
D. Canistro1, A. Sapone1, S. Melega1, M. Paolini1.
1Dept. of Pharmacology, Alma Mater Studiorum-University of Bologna, via Irnerio 48-40126 Bologna, Italy.
1Dept. of Pharmacology, Alma Mater Studiorum-University of Bologna, via Irnerio 48-40126 Bologna, Italy.
Abstract
In the last decades, several epidemiological and animal investigations indicated how high and varied fruits and vegetables intake could significantly reduce cancer risk and the development of cardiovascular and degenerative diseases. Fruits and vegetables rich in antioxidant nutrients are hypothesized to be chemopretective against many tumour types by several mechanisms, including reduction of reactive oxygen species responsible of oxidative damage, modulation of xenobiotic metabolising enzymes, regulation of cell survival and apoptosis pathways, protection of immune homeostasis. From here, long term administration of naturally occurring constituents, as well as exclusive consumption of single greens was seen as a valid strategy to counteract cancer incidence. Apples provide a great source of salutary phytochemicals in human diet. Their healthy properties have been highlighted by recent studies reporting how apple consumption could be correlated with reduction in risk of stroke, heart disease and lung cancer.
In this scenario, the ability of Golden Delicious apples to boost Phase-II (“detoxifying”) and/or down-regulate Phase-I (“activating”) enzymes was evaluated in the animal model. In particular, the chemopreventive potential of “organic” vs “integrated” cultivars was compared.
Swiss Albino CD1 male mice were daily treated (by gavage, for 7 or 14 consecutive days) with lyophilised apples at 250 or 500 mg/Kg (corresponding to 2 or 4 servings in a 70 Kg man) and liver, lung and kidney subcellular preparations tested for various CYP-linked monooxygenases.
A complex pattern of CYP manipulation was observed: in kidney, for example, CYP1A1 was actually increased up to 668%, whereas in lung, CYP3A1/2 and CYP1A1 were down-regulated (57% and 84% loss, respectively). In liver, both mild inductions and inactivations were reported.
No substantial differences between “organic” and “integrated” cultivars were seen.
The extensive metabolism manipulation we recorded, suggests caution in proposing the apple mono-diet as chemopreventive strategy. Noteworthy, the recent literature indicates that only an assorted fruit and vegetable rich diet, poor in fat, could be correlated with reduced cancer risk.
In this scenario, the ability of Golden Delicious apples to boost Phase-II (“detoxifying”) and/or down-regulate Phase-I (“activating”) enzymes was evaluated in the animal model. In particular, the chemopreventive potential of “organic” vs “integrated” cultivars was compared.
Swiss Albino CD1 male mice were daily treated (by gavage, for 7 or 14 consecutive days) with lyophilised apples at 250 or 500 mg/Kg (corresponding to 2 or 4 servings in a 70 Kg man) and liver, lung and kidney subcellular preparations tested for various CYP-linked monooxygenases.
A complex pattern of CYP manipulation was observed: in kidney, for example, CYP1A1 was actually increased up to 668%, whereas in lung, CYP3A1/2 and CYP1A1 were down-regulated (57% and 84% loss, respectively). In liver, both mild inductions and inactivations were reported.
No substantial differences between “organic” and “integrated” cultivars were seen.
The extensive metabolism manipulation we recorded, suggests caution in proposing the apple mono-diet as chemopreventive strategy. Noteworthy, the recent literature indicates that only an assorted fruit and vegetable rich diet, poor in fat, could be correlated with reduced cancer risk.