Stanozolol treatment decreases the mitochondrial ROS generation and oxidative stress induced by acute exercise in rat skeletal muscle

Journal Title (Medline/Pubmed accepted abbreviation): J Appl Physiol
Year: 2011
Volume: 110
Page numbers:661-669
doi (if applicable): 10.1152/japplphysiol.00790.2010

Summary of Background and Research Design

Background: Although anabolic androgenic steroids are commonly used to increase muscle mass and improve muscle fatigue resistance, little is known about their actual mechanism of action in skeletal muscle. Previous research supports a role for sex hormones in redox homeostasis. Specifically, it has been suggested that anabolic androgenic steroids function by modulating reactive oxygen species (ROS), which are critical at low levels for muscle contractility and are increased in muscle tissue during exhaustive exercise.

Hypothesis/purpose of study: Anabolic androgenic steroids protect skeletal muscle mitochondria from exercise-induced oxidative modification by modulating mitochondrial ROS generation and/or scavenging.

Subjects: Thirty-two 8-week old Wistar rats (initial body weight, 283 ± 7 g) were included in the study.

Experimental design: Randomized, preclinical

Treatments and protocol: Rats were randomized to 2 groups, control and stanozolol-treated (2 mg/kg body wt by gavage, 5 times/wk). After 8 weeks, 8 rats from each group were selected to perform exhaustive exercise on a motor-driven treadmill while the other 8 from each group remained sedentary. All rats were sacrificed immediately after, and mitochondria were isolated from the gastrocnemius muscles. The rate of oxygen consumption, H2O2 generation, aconitase enzymatic activity, markers of protein oxidation (glutamic semialdehyde [GSA], aminoadipic semialdehyde [AASA]), markers of glycoxidation (carboxymethyl-lysine [CML], carboxyethyl-lysine [CEL]), and lipoxidation (malondialdehyde-lysine [MDAL]) were determined to measure oxidative stress-induced damage. Fatty acyl groups were quantitated to determine cell membrane composition.

Summary of research findings:
  • There were no differences in oxygen consumption between the treatment groups
  • Compared with control rats after exercise, stanozolol-treated rats had a higher mitochondrial content of saturated and mono-unsaturated fatty acids and a lower content of highly unsaturated fatty acids (docosahexaenoic).
  • Stanozolol treatment inhibited
    -   Exercise-induced increases in all protein oxidation markers evaluated (P < .05)
    -   Exercise-induced increases in H2O2 production with complex I or II-linked substrates (P < .05)
    -   Exercise-induced decreases in mitochondrial aconitase activity (P < .05)
    • Stanozolol had no effect on aconitase activity in sedentary animals.
  • Stanozolol-treated sedentary rats had no marked differences from control sedentary rats except for some oxidation markers.
    -   Stanozolol treatment reduced baseline levels of GSA, CEL, and MDAL in sedentary rats compared to control sedentary rats (P < .05).

Interpretation of findings/Key practice applications:

These results suggest that stanozolol, and by extension anabolic androgenic steroids, preserves mitochondrial function during acute exercise. Treatment with stanozolol protected rat skeletal muscle tissue from exercise-induced protein oxidative damage and changes in membrane fatty acid composition. The mechanism of protection appears to be attributed to decreased production of mitochondrial ROS generation in response to exercise and not changes in enzymatic activity. Interestingly, increased intracellular ROS generation in response to exercise does provide some physiologic benefits, and it has previously been demonstrated that administration of high-dose antioxidant supplementation prevents some beneficial ROS-mediated cellular changes that are induced by exercise. Therefore, stanozolol treatment could actually decrease endurance training efficiency. Further work is needed to study this point and also to study the long-term safety of anabolic steroids as they are linked to potential hepatotoxicity.
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