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Assessing the effects of deprenyl on longevity
and antioxidant defenses in different animal models
Kitani K, Kanai S, Ivy GO, Carrillo MC
National Institute for Longevity Sciences,
Aichi, Japan.
Ann N Y Acad Sci 1998 Nov 20; 854:291-306
ABSTRACT
Among many pharmaceuticals that have been tested
for their effects on longevities of different animal rodents, deprenyl is
unique in that its effects on longevity has been tested in at least four
different animal species by independent research groups and that the effect
has been postulated to be due to its effect of raising such antioxidant
enzyme activities as superoxide dismutase (SOD) and catalase (CAT) in
selective brain regions. Thus far, in all four species of animals examined
(rats, mice, hamsters, and dogs), a positive effect was demonstrated,
although the extent of its effect is quite variable. Our group has examined
the effect on longevities in rats and mice and on antioxidant enzymes in
rats, mice, and dogs. Although in rats of both sexes, we have obtained
positive effects on longevity, two studies with different doses in mice did
not reveal a significantly positive effect. We have observed, however,
significantly positive effects on SOD (in Cu, Zn-, and Mn-) as well as CAT
(but not glutathione peroxidase) activities in the brain dopaminergic system
such as in the S. nigra and striatum (but not in hippocampus) in all rats,
mice, and dogs, although the effects were quite variable, depending on the
doses used. In mice, however, a long-term administration (3x/w, 3 months)
caused a remarkable decrease in the magnitude of activity as well as a
narrowing of the effective dose range, which may explain a relatively weak
effect of the drug on mouse longevity. Further, a recent study on aging
beagle dogs by Ruehl et al. showed a remarkable effect on longevity, which
agrees with our SOD study in dogs. Although deprenyl has been claimed to
have several other effects, such as a radical scavenging effect and a
neuroprotective effect, past reports on its effects on longevities and
antioxidant defenses are compatible with the notion that the drug prolongs
the life span of animals by reducing the oxidative damage to the brain
dopaminergic system during aging. Further, our studies on F-344 rats as
well as a dog study by Ruehl et al. suggest that the drug may at least
partially prolong the life span of animals by enhancing immune system
function and preventing tumor development in animals.
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