Effects of Phentermine and Phenformin on Biomarkers of Aging in Rats

Abstract

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 β-lipoprotein and pre-β-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°C) was significantly higher than in the ad libitum fed (37.8°C) and pair-fed (37.6°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 le...

Protective effects of phenformin on zebrafish embryonic neurodevelopmental toxicity induced by X-ray radiation

“…SOD and CAT are the first lines of defence against superoxide and hydrogen peroxide accumulation, while MDA is an end product of lipid peroxidation often measured as a index of lipid peroxidation. In the present study, irradiation dramatically reduced SOD and CAT activities and enhanced MDA accumulation, consistent with oxidative stress, while phenformin pre-treatment reversed these effects, consistent with the previous report that treatment with phenformin decreased ROS generation in caloric restriction rat [44].…”

Antidiabetic Effect of an Active Components Group fromIlex kudingchaand Its Chemical Composition

“…In addition, mice treated with phenformin showed an increased superoxide dismutase level and decreased malondialdehyde level compared to that of model mice. The effectiveness was reported previously [21]. …”

Caloric restriction

“…These drugs had rather modest effects on body weight and therefore did not seem to be acting by suppressing food intake. Direct measures of food intake confirm phenformin does not reduce food intake (Anisimova et al, 2005). However, phenformin also had no effect on T b and the effects on ROS production were equivocal.…”

“…Moreover contrasting the normal response to CR the mean rectal temperature in the phentermine group (38°C) was slightly but significantly higher than in the AL group (37.8°C). Treatment with phentermine did however result in significantly reduced ROS levels paralleling the effect in CR (Anisimova et al, 2005). The T b effects suggest that 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.…”