Oxidative stress is considered to be of major relevance for a variety of pathological processes. Thus,
it is valuable to identify compounds, which might act as antioxidants, i.e. compounds that
antagonize the deleterious action of reactive oxygen species (ROS) on biomolecules. The mode of
action of these compounds could be either to scavenge ROS directly or to trigger protective
mechanisms inside the cell, thereby resulting in improved defense against ROS. Sulforaphane (SF)
(1-isothiocyanato-(4R)-(methylsulfinyl)butane) is a naturally occurring cancer chemopreventive
agent found as a precursor glucosinolate in Cruciferous vegetables like broccoli. Although SF is not
a direct-acting antioxidant, there is substantial evidence that SF acts indirectly to increase the
antioxidant capacity of animal cells and their abilities to cope with oxidative stress. Induction of
phase 2 enzymes is one means by which SF enhances the cellular antioxidant capacity. Enzymes
induced by SF include Glutathione S-transferases (GST) and NAD[P]H:quinone oxidoreductase
(NQO1) which can function as protectors against oxidative stress. To protect themselves from
oxidative stress, cells are equipped with reducing buffer systems including the GSH and thioredoxin
(Trx) reductase. GSH is an important tripeptide thiol which in addition to being the substrate for
GSTs maintains the cellular oxidation– reduction balance and protects cells against free radical
species.
Aim of the first part of this thesis was to investigate the ability of SF to induce the expression and
the activity of different phase 2 and antioxidant enzymes (such as GST, GR, GPx, NQO1, TR,
SOD, CAT) in an in vitro model of rat cardiomyocytes, and also to define if SF treatment supprts
cells in counteracting oxidative stress induced by H2O2
It is well known that acute exhaustive exercise causes significant reactive oxygen species
generation that results in oxidative stress, which can induce negative effects on health and well
being. In fact, increased oxidative stress and biomarkers (e.g., protein carbonyls, MDA, and 8-
hydroxyguanosine) as well as muscle damage biomarkers (e.g. plasmatic Creatine cinase and
Lactate dehydrogenase) have been observed after supramaximal sprint exercises, exhaustive longdistance
cycling or running as well as resistance-type exercises, both in trained and untrained
humans. Markers of oxidative stress also increase in rodents following exhaustive exercise.
Moreover, antioxidant enzyme activities and expressions of antioxidant enzymes are known to
increase in response to exhaustive exercise in both animal and human tissues.
Aim of this project was to evaluate the effect of SF supplementation in counteracting oxidative
stress induced by physical activity through its ability to induce phase 2, and antioxidant enzymes in
rat muscle.
The results show that SF is a nutraceutical compound able to induce the activity of different phase 2
and antioxidant enzymes in both cardiac muscle and skeletal muscle. Thanks to its actions SF is
becoming a promising molecule able to prevent cardiovascular damages induced by oxidative stress
and muscle damages induced by acute exhaustive exercise.
| Identifer | oai:union.ndltd.org:unibo.it/oai:amsdottorato.cib.unibo.it:781 |
| Date | 17 June 2008 |
| Creators | Malaguti, Marco <1979> |
| Contributors | Biagi, Pierluigi |
| Publisher | Alma Mater Studiorum - Università di Bologna |
| Source Sets | Università di Bologna |
| Language | Italian |
| Detected Language | English |
| Type | Doctoral Thesis, PeerReviewed |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess |
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