Effects of the anti-oxidant PDTC in combination with a single bout of treadmill running on murine skeletal muscle

Abstract

Objectives: Skeletal muscle adaptation to physical activity is dependent on various factors. Important signaling mediators are reactive oxygen species (ROS). However, recent research suggests that ROS have both beneficial and deleterious effects on exercise adaptation, dependent on training intensity and training status, so that the question of whether anti-oxidants should be taken in connection with exercise cannot easily be answered. Thus, it is important to gain more insight into the complex roles of ROS in regulating training adaptation. Methods: The effects of ROS inhibition on skeletal muscle training adaptation were analyzed by applying the anti-oxidant PDTC, which is also an inhibitor of the ROS-activated transcription factor nuclear factor kappa B (NFκB), to juvenile mice in connection with a single bout of treadmill running. Results: We found that PDTC inhibits exercise-mediated induction of specific stress-and inflammation-associated genes. Other genes, specifically those encoding metabolic and mitochondrial factors, were affected to a lesser extent and there appeared to be little effect on the microRNA (miR) profile. Discussion: Our data suggest that anti-oxidants regulate distinct sets of adaptation-relevant genes, which might have important implications for the design of exercise-based preventive and therapeutic approaches.

Skeletal muscle effects of two different 10‐week exercise regimens, voluntary wheel running, and forced treadmill running, in mice: A pilot study

“…The metabolic marker Nr4a3 was downregulated in S, TA, and G. This might be due to the fact that despite the finding that this gene is strongly induced in response to acute exercise, regular training appears to exert no or even a slight inhibitory effect on its expression (for review, see Pillon et al., 2020, and references therein). This hypothesis is supported by the fact that a single bout of moderate‐intensity FTR, comparable with one training session within the regimen described here, led to a strong induction of Nr4a3 expression in both G (6.9‐fold) and T (3.9‐fold) in our hands (Schmitt et al., 2020).…”

Reduced Expression of Metallothionein-I/II in Renal Proximal Tubules Is Associated with Advanced Chronic Kidney Disease

“…Our results indicate that PDTC injection significantly improved AAI-induced renal fibrosis and reduced BUN and CRE in the AAN mice ( Figure 5 and Figure 6 ). Instead of inducing MT-I/II, PDTC has been extensively used for NFκB inhibition, metal chelation [ 29 ], and anti-oxidative stress [ 30 , 31 , 32 ]. The molecular mechanism by which PDTC induces MT-1/II expression and attenuates renal injury in AAN warrants further investigation.…”

The ROS scavenger PDTC affects adaptation to treadmill running in mice: distinct effects on murine body mass, resting heart rate and skeletal muscle fiber type composition

“…PDTC was administered with the drinking water at an approximate daily dose of 5 mg kg −1 during the familiarization week, 10 mg kg −1 during the first week of training, and 20 mg kg −1 from the second week of training onwards. PDTC dosage was chosen based on literature data and previous results of our group (Schmitt et al, 2018(Schmitt et al, , 2020, and references therein).…”