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Published on: November 7, 2017
PAG Masked Protective Physical Exercise-Induced High H2S Levels in 5/6 Nephrectomized Rats
Behjat Seifi1, Mehri Kadkhodaei1, Enayatollah Bakhshi2
1Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Background:
To investigate the mechanisms of exercise therapeutics in preclinical animal models of chronic kidney disease (CKD), PAG (D, L-propargylglycine), an inhibitor of hydrogen sulfide production, was used to examine the protective effects of physical activity on oxidative stress and inflammation levels during CKD.
Methods:
Male Wistar rats with CKD, induced by the 5/6 nephrectomy procedure and subjected to 8 weeks of exercise training, received injections of PAG, a cystathionine γ-lyase (CSE) inhibitor, at a dose of 19 mg/kg, i.p., twice a week during those 8 weeks. The systolic blood pressure (BP) and renal sympathetic nerve activity (RSNA) were assessed. Additionally, plasma creatinine, BUN, renal hydrogen sulfide (H2S) levels, oxidative stress, and inflammatory markers were evaluated.
Results:
In the PAG group, inhibition of H2S production significantly reversed the improvements in plasma creatinine, BUN, renal malondialdehyde (MDA) level, superoxide dismutase (SOD) activity, TNF-α, and IL-6 that were achieved by exercise. Additionally, high RSNA and high BP, which were also reversed in the PAG group, compared to the CKD group subjected to exercise training.
Conclusions:
The results suggest that the improvement in BP, oxidative stress, and inflammation status by exercise in CKD may be at least partially due to CSE/H2S signaling.
