Effect of long-term moderate-exercise combined with metformin-treatment on antioxidant enzymes activity and expression i

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RESEARCH ARTICLE

Effect of long-term moderate-exercise combined with metformin-treatment on antioxidant enzymes activity and expression in the gastrocnemius of old female Wistar rats ´ lvarez . Stefanie Paola Lo´pez-Cervantes . Ulalume Herna´ndez-Arciga . David Herna´ndez-A Norma Edith Lo´pez-Dı´azguerrero . Adriana Alarco´n-Aguilar . Armando Luna-Lo´pez . Mina Ko¨nigsberg Received: 27 May 2020 / Accepted: 30 July 2020 Ó Springer Nature B.V. 2020

Abstract Oxidative stress is known to be involved in the etiology of sarcopenia, a progressive loss of muscle mass and force related to elderly incapacity. A successful intervention to prevent this condition has been exercise-based therapy. Metformin (MTF), an anti-diabetic drug with pleiotropic effects, is known to retain redox homeostasis. However, the combined use of MTF with exercise has shown controversial experimental results. Our research group has shown that MTF-treatment does not limit the benefits provided by exercise, probably by inducing a hormetic response. Hence, our aim was to evaluate the effect of exercise in combination with MTF-treatment on the redox state of old female Wistar rats. Animals were divided into six groups; three groups preformed exercise on a treadmill

for 5 days/week for 20 months and the other three were sedentary. Also, two groups of each, exercised and sedentary animals were treated with MTF for 6 or 12 months correspondingly, beside the untreated groups. Rats were euthanized at 24 months. Muscular functionality was analyzed as the relation between the lean mass free of bone with respect to the grip strength. Superoxide dismutase, catalase, and glutathione peroxidase content, enzymatic activity and redox state were determined in the gastrocnemius muscle. Our results showed that the exercised group treated with MTF for 12 months presented higher GSH/GSSG rate and high antioxidant scavenging power in contrast to the MTF-treatment for 6 months, where the beneficial effect was less noticeable.

Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10522-020-09894-8) contains supplementary material, which is available to authorized users. ´ lvarez  U. Herna´ndez-Arciga  D. Herna´ndez-A S. P. Lo´pez-Cervantes  N. E. Lo´pez-Dı´azguerrero  A. Alarco´n-Aguilar  M. Ko¨nigsberg (&) Lab. Bioenerge´tica y Envejecimiento Celular, Depto de Ciencias de la Salud, Universidad Auto´noma Metropolitana-Iztapalapa, A.P. 55-535, C.P. 09340 Ciudad de Me´xico, Mexico e-mail: [email protected]

S. P. Lo´pez-Cervantes Posgrado en Biologı´a Experimental, Universidad Auto´noma Metropolitana-Iztapalapa, Ciudad de Me´xico, Mexico A. Luna-Lo´pez Instituto Nacional de Geriatrı´a, SSA, 10200 Ciudad de Me´xico, Mexico

´ lvarez D. Herna´ndez-A Posgrado en Ciencias Biolo´gicas, Universidad Auto´noma Metropolitana, Ciudad de Me´xico, Mexico

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Biogerontology

Graphic abstract

Enzymac acvity • SOD • CAT • GPx

METFORMIN

Western Blot • • • •

SOD CAT GPx Nrf2

GASTROCNEMIUS