Changes induced by aging and drug treatment on cerebral enzymatic antioxidant system

Abstract

The age-related modifications of the participants to the cerebral enzymatic antioxidant system (superoxide dismutase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase) were evaluated in four brain regions from male Wistar rats aged 5, 10, 15, 20, 25, 30, and 35 months. Both the specific enzyme activity and the profile of any enzyme tested markedly differ with age according to the region examined: parieto-temporal cortex, caudate-putamen, substantia nigra and thalamus. This inhomogeneous age-related profile of enzyme activities could explain both the controversial data of literature and the different regional vulnerability of the brain tissue to damage with aging. In rats aged 10, 20, or 30 months, the chronic i.p. treatment for two months with papaverine or ergot alkaloids (dihydroergocristine, dihydroergocornine, dehydroergocriptine) suggests that the antioxidant enzyme activities may be influenced according to the agent utilized, the brain region tested, and the age of the animal. In any case, small differences in the drug structure support marked differences in the type and extent of the intervention on the antioxidant enzymatic system.

Changes on cerebral antioxidant enzymes, peroxidation, and the glutathione system of frogs after aging and catalase inhibition

“…In the majority of studies, a comprehensive approach was not selected, and many contradictory results have been reported. Thus, total SOD, Se-GPx, or GR, decreased (Hothersall et al, 1981;Benzi et al, 1988a;Vanella et al, 1989), did not change (Keilogg and Fridovich, 1976;Mizuno and Ohta 1986;Cand and Verdetti, 1989), or even increased (Hothersall et al, 1981;Danh et al, 1983;Victorica, 1984;Tayarami et al, 1989) in the brains of aged rats. Brain cumene-OOH GPx and CAT were smaller in the brain of old compared with young rats (Cand and Verdetti, 1989).…”

“…Part of these discrepancies can be attributed to differences in the strain or age selected. Thus, in some studies, not fully mature animals (4 months) were selected as "young" (Cand and Verdetti, 1989), whereas in other works clear decreases were observed in very old rats (35 months), but not in senescent individuals (25 months) (Benzi et al, 1988a). Nevertheless, it seems from these data that aging in the rat is not accompanied by increases of oxidative stress and decreases in antioxidant defenses in a way so marked as in the housefly.…”

“…In these studies, pcrformed almost exclusively in the brain of rats, contradictory results about the pattern of variation during aging of various antioxidants, such as superoxidc dismutase (SOD) (Kellogg and Fridovich, 1976;Massie et al, 1979;Vanella ct al., 1982Vanella ct al., , 1989Benzi et al, 1988a;Tayarami et al, 19891, selenium (Se)-dependent glutathione peroxidase (GPx) (Hothersall et al, 1981 ;Vitorica ct al., 1984;Mizuno and Ohta, 1986;Benzi et al, 1988a;Tayarami eta]., 1989), glutathione reductase (GR) (Hothersall et al, 1981;Benzi et al, 1988a;Tayarami et al, 1989), and reduced glutathione (GSH) (Benzi et al, 1988b;Rikans and Moore, 1988) have been reported. These disparities can be due to differences in methodology among laboratories and to the lack of simultaneous measurement of the majority of the relevant parameters related to free-radical damage in thc same animals.…”

Pharmacological Enhancement of Neuronal Survival

“…However, it wasn't until the late 1980s that it was found to induce cerebral antioxidant enzyme activation (Benzi et al, 1988;Gorini et al, 1988), thereby making it a candidate neuroprotective drug. To this end, Favit et al (1993) evaluated whether DECP could prevent induced neurotoxicity via several experimental approaches, including aged-related neurodegeneration and glutamate-induced neurotoxicity.…”

Targeting antioxidant enzyme expression as a therapeutic strategy for ischemic stroke

“…Benzi et al reported that activities of GSH-PX, glutathione reductase, and SOD decrease in the parieto-temporal cortex, striatum, substantia nigra, and thalamus in rats aged 15–30 months of age compared to younger rats (Benzi et al, 1988). …”