title: Effects of stimulation of autophagy on the urinary excretion of biomarkers of the oxidative status.
abstract: Autophagy, a health-promoting lysosomal degradation pathway that controls the quality of the cytoplasm by eliminating protein aggregates and damaged organelles including 8-OHdG-rich mitochondria, is under investigation as a target for prevention and/or treatment of several human diseases and decelerating aging. Stimulation of autophagy was shown to rescue older liver cells from accumulation of 8-OHdG-rich mitochondria and to increase urinary 8-OHdG levels. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a recently recommended biomarker for monitoring oxidative status over time. In order to rule out the possibility that the in vivo stimulation of autophagy may cause an increase in the oxidative status, in this study we compared the effects of the stimulation of autophagy by two different procedures (the administration of antilipolytic drug and everolimus, an mTOR inhibitor in clinical use) on the urinary levels of 8-OHdG and 15-isoprostane F2t, another well-known biomarker of the oxidative status. Results show that both procedures increased the urinary 8-OHdG levels without any change in urinary 15-isoprostane F2t; this increase in urinary 8-OHdG levels after the antilipolytic drug was fully suppressed by the simultaneous injection of glucose to make rats transiently incompetent for the endocrine stimulation of autophagy. Conclusions are that the in vivo stimulation of autophagy does not affect the oxidative status and that the increasing effect on urinary 8-OHdG may be secondary to an increased degradation of previously accumulated 8-OHdG-rich (mt)DNA. The authors are aware that findings may open the way to a safe, easy, highly desirable non-invasive test for successful in vivo activation of autophagy after pharmacological stimulation.
authors: Interdepartmental Research Centre on Biology and Pathology of Aging, University of Pisa, Via Roma 55, 56126, Pisa, Italy, gabriella.cavallini@med.unipi.it.
authors: Gabriella
authors: G
authors: Cavallini
authors: Alessio
authors: A
authors: Donati
authors: Biagio
authors: B
authors: Capasso
authors: Michele
authors: M
authors: Fella
authors: Vincenzo
authors: V
authors: Leone
authors: Gaetano
authors: G
authors: Pezzella
authors: Giorgio Cosimo
authors: GC
authors: Romano
authors: Angelo
authors: A
authors: Vagali
authors: Ettore
authors: E
authors: Bergamini
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D015415:Biomarkers / Q000652:urine; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D015237:Dinoprost / Q000031:analogs & derivatives; D005947:Glucose / Q000494:pharmacology; D028421:Isoprostanes / Q000652:urine; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015415:Biomarkers; D028421:Isoprostanes; C075750:8-epi-prostaglandin F2alpha; D000080242:8-Hydroxy-2'-Deoxyguanosine; D015237:Dinoprost; D003849:Deoxyguanosine; D005947:Glucose