Why (−)deprenyl prolongs survivals of experimental animals: Increase of anti-oxidant enzymes in brain and other body tissues as well as mobilization of various humoral factors may lead to systemic anti-aging effects

Kitani, Kenichi; Minami, Chiyoko; Isobe, Ken‐ichi; Maehara, Kayoko; Kanai, Setsuko; Ivy, Gwen O.; Carrillo, Maria-Cristina

doi:10.1016/s0047-6374(01)00392-x

Cited by 63 publications

(67 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Deprenyl also mobilizes a variety of humoral factors such as interleukines, neuronal factors (including neurotrophins), hormonal factors etc. (Kitani et al 2002a). Some of these appear to be related to the up-regulation of antioxidant enzyme activities induced by this drug.…”

Section: Pharmacological and Nutritional Interventions In Agingmentioning

confidence: 99%

What really declines with age?

Kitani¹

2007

AGE

Self Cite

View full text Add to dashboard Cite

In order to understand the basic mechanisms underlying the organismic aging process, considerable efforts have been devoted in the last half-century to biochemical (enzyme activity) alterations in specific tissues and organs of various organisms associated with aging. When a decline in enzyme activities with age has been found in a study, especially for key enzymes such as antioxidant enzymes, the results have often been interpreted as a cause for the aging of the entire body. Retrospectively, however, these changes turned out to be so variabledepending on species, strains and sexes of animalsthat the interpretation of these results in general terms of aging became invalid. Further, unlike the prediction for the whole human body, many enzyme activities in a vital organ, such as the liver, remained unchanged, as long as the old subjects remained healthy. However, enzyme activities in old animals and humans are often more susceptible to morbidities and frailties, which themselves are often accompanied by infections and malnutrition. Despite the rather stable enzyme functions in the liver with age, a distinct and progressive decline in the lateral diffusion coefficient of proteins of hepatocyte plasma membranes has been demonstrated by fluorescence recovery after photobleaching (FRAP), which was implicated as the cause for the decline of hepatocyte functions such as ouabain (and taurocholate) hepatic uptake and their eventual biliary excretion. Since a similar decline in protein diffusion coefficients was observed in brain and muscle cells, it is likely that these changes are occurring in common with many cell types of the body, thus causing a delay in transmembrane transport of endogenous and exogenous substances whose transports are mediated by membrane proteins. In attempts to prolong the life spans of animals other than by calorie restriction, but instead using deprenyl or tetrahydrocurcumin, works by the author and coworkers are introduced and discussed. Despite limited success along these lines thus far, further attempts are encouraged, primarily to understand the mechanisms underlying organismic aging processes and to find a practical way to prolong the health span of the elderly.

show abstract

Section: Pharmacological and Nutritional Interventions In Agingmentioning

confidence: 99%

What really declines with age?

Kitani¹

2007

AGE

Self Cite

View full text Add to dashboard Cite

show abstract

“…These findings confirmed that selegiline central administration attenuates morphine dependence. Its worth mentioning that selegiline as a selective monoamine oxidase B inhibitor, has neuroprotective properties which has been confirmed by several studies, and is used for treatment of Parkinson disease [6,19,31]. In addition to MAO inhibitor effects, selegiline has anti-apoptotic and pro-trophic factor properties [26][27][28][29][30][31][32][33][34][35].…”

Section: Discussionmentioning

confidence: 99%

Repeated central administration of selegiline attenuated morphine physical dependence in rat

Parvizpour

Charkhpour

Habibiasl

et al. 2013

Pharmacological Reports

View full text Add to dashboard Cite

Abstract:Background: Long-term exposure to opiates induces physical dependence; however, the neurobiological mechanisms of this phenomenon are not completely clear. The purpose of this study was to evaluate the effects of systemic and intracerebroventricular (icv) administration of selegiline (a selective inhibitor of monoamine oxidase B) on the morphine withdrawal syndrome in rats. Methods: To this aim, adult male Sprague Dawley rats were selected randomly, and then growing doses of morphine were administered subcutaneously at an interval of 12 h for nine days with the intention of inducing dependency. Nine days after, only the morning dose of morphine was administered, followed by systemic or central injection of saline or selegiline. Later, naloxone was injected after 30 min and withdrawal signs recorded for a period of 60 min. Results: Results showed failure of systemic administration of selegiline in changing the withdrawal symptoms; nevertheless, icv injection attenuated the withdrawal signs significantly. Conclusion: In conclusion we found that central administration of selegiline attenuated morphine withdrawal symptoms

show abstract

“…Based on preliminary evidence in our laboratory, we propose similar effects of estrogen on the loss of sympathetic NA innervations in the spleens of tumor-bearing rats. The deprenyl-mediated reinnervation of the sympathetic nerves in the spleen and restored NE content in tumor-bearing rats as well as its inhibition of tumor development may result from increased growth-factor biosynthesis and/or enhanced free radical scavenging by antioxidant enzymes, such as superoxide dismutase and catalase [11,14]. …”

Section: Discussionmentioning

confidence: 99%

“…L -Deprenyl, a monoamine oxidase inhibitor, has been used as a therapeutic agent in Parkinson's and Alzhei-mer's disease because of its ability to increase the availability of catecholamines, augment the activities of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) and growth-factor biosynthesis, and improve neuronal survivability [11,12,13,14]. Previously, we demonstrated that the administration of deprenyl or its metabolite, desmethyldeprenyl, to old male rats reversed the age-related decline in splenic NA innervation and enhanced splenic concanavalin A (Con A)-induced interleukin (IL)-2 production and NK cell activity [15,16].…”

Section: Introductionmentioning

confidence: 99%

Prevention of Mammary Tumor Development through Neuroimmunomodulation in the Spleen and Lymph Nodes of Old Female Sprague-Dawley Rats by <smlcap>L</smlcap>-Deprenyl

ThyagaRajan¹,

Tran²,

Molinaro³

et al. 2013

Neuroimmunomodulation

View full text Add to dashboard Cite

Background: Development of mammary tumors is an age-associated phenomenon that is likely due to deficits in the neuroendocrine-immune interactions. Previously, we demonstrated that L-deprenyl, a monoamine oxidase-B (MAO-B) inhibitor, can enhance immune responses and restore noradrenergic (NA) innervation in the spleens of rats with carcinogen-induced and spontaneously developing mammary tumors. Objectives: To investigate whether (1) treatment of early middle-aged female rats would prevent the spontaneous development of mammary tumors accompanied by restoration of immunity in the spleen and draining lymph nodes (DLN) and sympathetic NA innervation in the spleen and (2) deprenyl can influence the proliferation of estrogen receptor (ER)-positive (MCF-7 and T47D) and ER-negative (MDA-MB-231 and Hs 578T) human breast cancer cells. Methods: Early middle-aged (8- to 9-month-old) female Sprague-Dawley rats were treated with 0, 1.0 or 2.5 mg of deprenyl/kg body weight (BW) daily i.p. for 12 months. Cells of ER-positive (ER+) and ER-negative (ER-) human breast cancer cell lines were incubated with media or 10^-3 to 10^-8M deprenyl for 1, 2, 4 or 6 days to examine the proliferation of cells. Results: Tumor incidence increased in saline-treated old female rats, while deprenyl treatment significantly reduced the incidence of mammary tumors in these rats. Saline-treated tumor-bearing rats exhibited reduced splenic NA innervation and norepinephrine (NE) content, splenic interleukin (IL)-2 and interferon (IFN)-γ levels and NK cell activity as well as DLN IL-2 and IFN-γ levels compared to young female rats without tumors. In contrast, treatment with 2.5 mg/kg of deprenyl enhanced IL-2 and IFN-γ production in both the spleen and DLN as well as splenic natural killer (NK) cell activity. Deprenyl treatment also increased concanavalin A (Con A)-induced proliferation of T lymphocytes in the DLN. Deprenyl-induced changes in immune responses were accompanied by enhanced NA innervation and NE content in the spleen. In vitro incubation of various concentrations of deprenyl with ER+ human breast cancer cell lines partly inhibited the proliferation of cells, while it had no effect on the ER- breast cancer cells. Conclusions: These results suggest that (1) development of mammary tumors is mediated through the loss of immunity and sympathetic NA nerve fibers accompanied by reduced NE levels in the spleen, (2) the prevention of mammary tumor development by deprenyl may involve the reversal of the tumor-associated decline in sympathetic NA activity and cell-mediated immune responses in the spleen and DLN and (3) the antitumor effects of deprenyl may be partially mediated through ER-dependent intracellular signaling pathways.

show abstract

Why (−)deprenyl prolongs survivals of experimental animals: Increase of anti-oxidant enzymes in brain and other body tissues as well as mobilization of various humoral factors may lead to systemic anti-aging effects

Cited by 63 publications

References 56 publications

What really declines with age?

What really declines with age?

Repeated central administration of selegiline attenuated morphine physical dependence in rat

Prevention of Mammary Tumor Development through Neuroimmunomodulation in the Spleen and Lymph Nodes of Old Female Sprague-Dawley Rats by <smlcap>L</smlcap>-Deprenyl

Contact Info

Product

Resources

About