Pharmacological modifications of endogenous antioxidant enzymes with special reference to the effects of deprenyl: a possible antioxidant strategy.
Limited information is available on the upregulation of endogenous antioxidant enzymes by means of administering various pharmaceuticals and/or chemicals. It has been reported that ursodeoxycholic acid (UDCA), a bile acid originally identified from black bear bile (a Chinese medicine, Yutan) increased glutathione S-transferase (GST) activities in mouse livers, resulting in a decrease in systemic lethal toxicity of orally challenged 1-2-dichloro-4-nitrobenzene (DCNB). Also, ursolic acid found in herbal medicines (e.g. leaves of loquat) was reported to increase catalase (CAT) activities in mouse liver. Interestingly, the chemical structures of these two compounds are surprisingly similar to each other, despite the difference in their original sources. These results suggest that in the future, more and more compounds will be found to have effects on increasing endogenous antioxidant enzyme activities. Deprenyl is a monoamine oxidase B inhibitor but also possesses many other different pharmacological activities. Among these various pharmacological effects of deprenyl, a possible causal relationship between two effects of deprenyl, namely the prolongation of the survival of animals and upregulation of antioxidant enzymes in selective brain regions, has been postulated by the authors. In at least four different animal species (rats, mice, hamsters and dogs), a significant prolongation of survival by chronic administration of the drug has been reported by different groups including that of the authors. This group has reported that repeated administration of the drug for 2-3 weeks can significantly increase activities of both types of superoxide dismutase (SODs) (Cu, Zn-, and Mn-SODs) as well as of CAT selectively in brain dopaminergic regions. Both effects are dose dependent but excessive dosages become less effective and even cause an adverse effect (i.e. a decrease in enzyme activities and shortening of life span). The parallelism of the dose-effect relationship between the two phenomena suggests that modification of SOD and CAT levels is one possible mechanism for deprenyl's ability to prolong the life span of animals.
Kitani
K
K
National Institute for Longevity Sciences, Aichi, Japan. kitani@nils.go.jp
Kanai
S
S
Ivy
G O
GO
Carrillo
M C
MC
D000375:Aging / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D002415:Cats; D006224:Cricetinae; D004285:Dogs; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009578:Nitrobenzenes / Q000494:pharmacology; D010088:Oxidoreductases / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D012642:Selegiline / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology; D015854:Up-Regulation; D014580:Ursodeoxycholic Acid / Q000494:pharmacology; D000097245:Ursolic Acid
D000975:Antioxidants; D002374:Catalase; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D008996:Monoamine Oxidase Inhibitors; D009578:Nitrobenzenes; D010088:Oxidoreductases; D012642:Selegiline; D013482:Superoxide Dismutase; D014315:Triterpenes; D014580:Ursodeoxycholic Acid; D000097245:Ursolic Acid; C028328:1,2-dichloro-4-nitrobenzene