PMID- 15591752
OWN - NLM
STAT- MEDLINE
DCOM- 20050519
LR  - 20220409
IS  - 0304-324X (Print)
IS  - 0304-324X (Linking)
VI  - 51
IP  - 1
DP  - 2005 Jan-Feb
TI  - Effects of phentermine and phenformin on biomarkers of aging in rats.
PG  - 19-28
AB  - BACKGROUND: Caloric restriction (CR) is the only treatment known to substantially 
      prolong both average and maximal life span in experimental animals. Interventions 
      that mimic certain effects of CR could be potential anti-aging treatments in 
      humans. Drugs which reduce appetite (anorexiants) represent one class of 
      candidate treatments. Agents that reduce the glucose utilization by the organism 
      could also represent another class of candidate CR mimetics. OBJECTIVE: In our 
      study, we addressed the following questions: (1) Does treatment with an 
      anorexiant reduce caloric intake and body weight of experimental animals 
      comparable to that caused by CR? (2) Does treatment with an antidiabetic agent 
      influence caloric intake and body weight? (3) Does treatment with any of these 
      drugs affect metabolic parameters of an organism in the way similar to that 
      observed with CR? METHODS: One hundred and twenty 6-month-old female 
      Wistar-derived LIO rats were randomly subdivided into four groups and exposed to: 
      (1) ad libitum feeding with placebo (controls); (2) the antidiabetic drug 
      phenformin (2 mg/kg); (3) the anorectic drug phentermine (1 mg/kg), and (4) the 
      same amount of food as the group with the least food intake during the previous 
      week (pair-fed controls). Food and water intake, body weight, and rectal 
      temperature were measured weekly during 16 weeks. At the end of the 16th week of 
      the experiment, serum levels of glucose, total beta-lipoprotein and 
      pre-beta-lipoprotein fractions, cholesterol, triglycerides, insulin, total 
      triiodothyronine, and free thyroxine were estimated. The contents of diene 
      conjugates and Schiff's bases, total antioxidant activity, the activities of 
      Cu/Zn superoxide dismutase, glutathione S-transferase, and glutathione 
      peroxidase, and the generation of reactive oxygen species (ROS) were studied in 
      brain and liver homogenates and in the serum. RESULTS: The controls exposed to 
      pair feeding had a significantly reduced food consumption (about 20%) as compared 
      with the ad libitum fed controls and thus exhibited a moderate CR. Treatment with 
      phentermine reduced the caloric intake by about 12% as compared with the ad 
      libitum fed controls. Body weight and water intake in this group were only 
      slightly decreased (by about 2 and 5%, respectively) as compared with the 
      controls. The mean rectal temperature in the phentermine group (38 degrees C) was 
      significantly higher than in the ad libitum fed (37.8 degrees C) and pair-fed 
      (37.6 degrees C) controls. Treatment with phentermine also resulted in 
      significantly reduced ROS levels in all tissues studied, while the highest ROS 
      production was found in ad libitum (blood serum) and pair-fed (brain) controls. 
      Treatment with phenformin did not significantly influence food and water 
      consumption, body weight, and temperature when compared with the ad libitum fed 
      controls. Rats treated with this antidiabetic drug showed intermediate values of 
      ROS generation. Differences among the groups in total antioxidant activity were 
      not obvious. CONCLUSIONS: Treatment with phentermine reduces caloric intake 
      slightly less than is commonly observed in CR studies. CR due to forcibly reduced 
      feeding and CR due to substance-suppressed appetite appear to act through 
      different metabolic mechanisms and thus may affect aging and longevity in 
      different ways.
CI  - Copyright (c) 2005 S. Karger AG, Basel
FAU - Anisimov, Vladimir N
AU  - Anisimov VN
AD  - N.N. Petrov Research Institute of Oncology, D.O. Ott Research Institute of 
      Obstetrics and Gynecology, St. Petersburg, Russia. aging@mail.ru
FAU - Ukraintseva, Svetlana V
AU  - Ukraintseva SV
FAU - Anikin, Ivan V
AU  - Anikin IV
FAU - Popovich, Irina G
AU  - Popovich IG
FAU - Zabezhinski, Mark A
AU  - Zabezhinski MA
FAU - Bertsein, Lev M
AU  - Bertsein LM
FAU - Arutjunyan, Alexander V
AU  - Arutjunyan AV
FAU - Ingram, Donald K
AU  - Ingram DK
FAU - Lane, Mark A
AU  - Lane MA
FAU - Roth, George S
AU  - Roth GS
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - Switzerland
TA  - Gerontology
JT  - Gerontology
JID - 7601655
RN  - 0 (Appetite Depressants)
RN  - 0 (Hypoglycemic Agents)
RN  - C045TQL4WP (Phentermine)
RN  - DD5K7529CE (Phenformin)
SB  - IM
MH  - Aging/*metabolism
MH  - Animals
MH  - Appetite Depressants/pharmacology
MH  - Body Temperature/drug effects/physiology
MH  - Body Weight/drug effects
MH  - Brain/drug effects/metabolism
MH  - Caloric Restriction
MH  - Drinking/drug effects/physiology
MH  - Energy Intake/*drug effects
MH  - Female
MH  - Hypoglycemic Agents/pharmacology
MH  - Liver/drug effects/metabolism
MH  - Models, Animal
MH  - Phenformin/*pharmacology
MH  - Phentermine/*pharmacology
MH  - Random Allocation
MH  - Rats
MH  - Rats, Wistar
EDAT- 2004/12/14 09:00
MHDA- 2005/05/20 09:00
CRDT- 2004/12/14 09:00
PHST- 2003/05/14 00:00 [received]
PHST- 2004/02/24 00:00 [accepted]
PHST- 2004/12/14 09:00 [pubmed]
PHST- 2005/05/20 09:00 [medline]
PHST- 2004/12/14 09:00 [entrez]
AID - 81430 [pii]
AID - 10.1159/000081430 [doi]
PST - ppublish
SO  - Gerontology. 2005 Jan-Feb;51(1):19-28. doi: 10.1159/000081430.