Medicina - EXPLORING THE IMPACT OF METFORMIN ON TESTICULAR AGING IN SYRIAN HAMSTERS
Congreso
Autoría:
Cavallotti Gomez, Alina ; Rossi, Soledad Paola ; Munduruca Pires, Thaisy ; Calandra, Ricardo Saúl ; Da Ros, Vanina Gabriela ; Cohen, Débora Juana ; Riaño Gómez, Juan Manuel ; BIANCHI, MARIA SILVIA ; Theas, María Susana ; Matzkin, María Eugenia ; Frungieri, Mónica BeatrizFecha:
2024Editorial y Lugar de Edición:
Fundación Revista MedicinaResumen *
Earlier, we described that testicular aging in the Syrian hamster is associated with increased inflammatory-oxidative events and reduced autophagy, and in vitro incubations of old hamster testes with metformin improved the physiological status. In vivo experiment offer long-term observations and greater physiological relevance than in vitro studies. Thus, in this work, 20-months old hamsters were supplemented for 2 months with 170 mg/kg body weight/day of metformin (equivalent to that 1.500 mg oral dose usually administered to patients with type 2 diabetes mellitus, kindly provided by Fund. Roemmers and Montpellier S.A) dissolved in drinking water. Control group received only drinking water. Body and testicular weights and blood glucose levels decreased in metformin-treated hamsters. Unexpectedly, metformin supplementation significantly increased the expression of inflammatory indicators (NLRP3, Nek7, caspase 1 and IL1β evaluated by RT-qPCR and Wb) and the levels of oxidative stress markers (lipid peroxidation determined by TBARS assay, catalase expression assessed by Wb and catalase activity quantified by a colorimetric assay). Metformin also reduced autophagy (increased p62 expression and diminished LAMP2 levels determined by Wb) and further impaired testicular histology (increased Sertoli cell vacuolization and premature detachment of spermatocytes and spermatids from seminiferous tubules) and steroidogenesis (diminished protein and mRNA StAR expression, as well as serum levels of LH and testosterone assessed by RIAs). Therefore, although our previous in vitro studies suggest that metformin may exert beneficial effects in the testis reducing local inflammatory-oxidative status and stimulating autophagy, contradictory results were seen in the in vivo experiment. Thus, testicular impact of metformin administration deserves further investigation in order to establish whether its anti-aging therapeutic potential in the testis should be reconsidered and/or disregarded. Información suministrada por el agente en SIGEVAPalabras Clave
METFORMINHAMSTERTESTISAGING