title: Combined effects of aging and in vitro non-steroid anti-inflammatory drugs on kidney and liver mitochondrial physiology.
abstract: OBJECTIVE
  Aging and drug-induced side effects may contribute to deteriorate mitochondrial bioenergetics in many tissues, including kidney and liver. One possibility is that the combination of both aging and drug toxicity accelerates the process of mitochondrial degradation, leading to progressive bioenergetic disruption. We therefore analyzed in vitro kidney (KM) and liver (LM) mitochondrial response to salicylate and diclofenac in old and adult animals.
  
  
  METHODS
  Male-Wistar adult (19-wks) and aged (106-wks) rats were used. In vitro endpoints of oxygen consumption and membrane potential were evaluated in non-treated conditions (vehicle) and in the presence of salicylate (0.5mM) and diclofenac (50μM). The susceptibility to calcium-induced permeability transition pore (MPTP) was assessed. Aconitase and C, -SH and MDA contents were measured. Apoptotic signaling was followed by measuring caspase 3, 8 and 9 activities, Bax, Bcl2 and CypD expression. ANT content was semi-quantified.
  
  
  RESULTS
  In general, animal age alone compromised KM state 3 and LM ADP lag phase while resulting in decreased resistance to the MPTP. Aging decreased LM CypD and increased Mn-SOD. Kidney caspase 9-like activity was lower in aged group. Salicylate and diclofenac induced KM and LM dysfunction. ADP lag phase in KM was further increased in the aged group in the presence of diclofenac. No further impairments were observed regarding drug toxicity adding to the aging process.
  
  
  CONCLUSIONS
  Aging impaired KM and LM function despite no detected alterations on oxidative stress and apoptosis. However, aging did not further exacerbate KM and LM frailty induced by salicylate and diclofenac.
authors.affiliation: Research Centre in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal.
authors.forename: Sílvia
authors.initials: S
authors.lastname: Rocha-Rodrigues
authors.forename: Estela
authors.initials: E
authors.lastname: Santos-Alves
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Coxito
authors.forename: Inês
authors.initials: I
authors.lastname: Marques-Aleixo
authors.forename: Emanuel
authors.initials: E
authors.lastname: Passos
authors.forename: João T
authors.initials: JT
authors.lastname: Guimarães
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Martins
authors.forename: Paulo J
authors.initials: PJ
authors.lastname: Oliveira
authors.forename: José
authors.initials: J
authors.lastname: Magalhães
authors.forename: António
authors.initials: A
authors.lastname: Ascensão
mesh_terms: D000367:Age Factors; D000375:Aging; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D004008:Diclofenac / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D008930:Mitochondria, Liver / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D020156:Salicylic Acid / Q000633:toxicity*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D004008:Diclofenac; D020156:Salicylic Acid; D002118:Calcium
keywords: Anti-inflammatory drugs; Bioenergetics; Elderly; Renal and hepatic toxicity