Pancreatic mitochondria functions are affected during acute endotoxemia

ADÁN AREÁN, JUAN SANTIAGO; VANASCO, VIRGINIA; VACCARO, MARÍA INÉS; PAPPALETTERA, BRUNO; ALVAREZ, SILVIA

CABA

Congreso; Reunión Anual de la Sociedad Argentina de Investigaciones Clínicas; 2023

The molecular mechanisms involved in the development of sepsisand endotoxemia are multifactorial and have not yet been fully elucidated.The pancreas is one of the organs affected early duringendotoxemia and sepsis, which could be relevant in the developmentof the disease at a systemic level. Given the inflammatory natureof this pathology, pancreatic mitochondria could be affected,compromising tissue bioenergetics. The objective of this work wasto analyze the state of mitochondrial function, regarding ATP productionand as a relevant source of active oxygen species, and therepair mechanisms that trigger experimental endotoxemia. FemaleSprague Dawley rats (45 days old) were treated i.p. with: vehicle(control); LPS 0.5 mg/kg (LPS 0.5) and LPS 8 mg/kg (LPS 8). Mitochondrialfunction is assessed by O2 consumption, ATP production,and mitochondrial membrane potential. LPS 0.5 group showed anATP production decreased only at 6h after LPS injection. On theother hand, LPS 8 group presented a similar decrease in ATP productionat 6h but this decrease being increased at 24h. Furthermore,LPS 8 animals also showed a significant drop (35%) in mitochondrialmembrane potential (control value: 147 ± 20 mV) and O2 productiondecreased 24h (control value: 62 ± 3 ng-at O/min mg protein). Onthe other hand, mitochondrial NOX4 activity was found significantlyincreased (5 times) only in LPS 8 group, from 6h after starting treatment.Finally, changes in protein expression related to mitochondrialdynamics, and structures compatible with mitophagy (assessed byTEM) were observed in both endotoxemia groups. Taken together,our results suggest a relevant role for mitochondria in the pancreaticconditions observed during endotoxemia. Greater knowledge of themitochondrial mechanisms that are activated in the pancreas duringendotoxemia could be of great relevance, since its possible modulationcould allow the development of new therapeutic strategies.