title: Effect of palladium α-lipoic acid complex on energy in the brain mitochondria of aged rats.
abstract: BACKGROUND
  According to the mitochondrial mutation theory of aging, the impairment of mitochondrial functions and decline of cellular bioenergetics are induced by highly reactive oxygen species (ROS). Supplementation with antioxidants may protect mitochondria against respiration-linked oxidative stress and reduce decay by preserving genomic and structural integrity. Several clinical studies have reported beneficial effects of α-lipoic acid (LA) administration in individuals with Alzheimer's disease, particularly improving their spatial orientation; however, no studies have been reported on the effects of palladium α-lipoic acid (Pd-LA).
  
  
  OBJECTIVE
  The current study examined the effects of the Pd-LA complex on mitochondrial energy status in the brains of aged rats.
  
  
  METHODS
  The study used male Wistar rats, some that were older than 24 mo and weighed approximately 350 ± 50 g and some that were younger than 24 mo and weighed approximately 175 ± 25 g. The research team divided the rats into 5 groups of 6 rats.
  
  
  METHODS
  The study was conducted at the Amala Cancer Research Centre in Amala Nagar, Thrissur, Kerala, India.
  
  
  METHODS
  Three groups of rats were controls: (1) young controls administered no solution, (2) aged controls administered 1 mL/kg of a 0.25% solution (PO) of sodium hydroxide (NaOH), and (3) positive aged controls treated with LA (7.6 mg/kg, PO) dissolved in an alkaline saline (0.25% NaOH, w/v). Two groups were intervention groups: (1) aged rats treated with 1.2 mg/kg of Pd-LA (PO) and (2) aged rats treated with 23.5 mg/kg of Pd-LA (PO). The research team administered the solutions once daily for 30 d. After 30 d, all animals were sacrificed.
  
  
  METHODS
  The research team evaluated serum transaminases, lactate dehydrogenase (LDH), serum urea, and creatinine. The activities of superoxide dismutase (SOD), catalase (CAT), and the levels of reduced glutathione (GSH) were determined in the blood samples. Krebs cycle dehydrogenases were evaluated in the brain mitochondria. Furthermore, the activities of the respiratory chain complexes I, III and IV as well as adenosine triphosphate (ATP) levels were estimated in the mitochondrial fraction.
  
  
  RESULTS
  The study found that Pd-LA elevated the mitochondrial ATP levels in the brains of aged rats by enhancing the activity of not only the Krebs cycle dehydrogenases but also complexes I and IV. Furthermore, Pd-LA improved the body weight and blood antioxidant status of aged rats without affecting the functions of liver or renal cells.
  
  
  CONCLUSIONS
  The results of the current study demonstrate that Pd-LA improves mitochondrial energy status in the brains of aged rats. The effects can be attributed to the enhancing effect on the Krebs cycle dehydrogenase and the activities of complexes I, III, and IV. The results further support the possible use of Pd-LA as an adjuvant treatment, together with the standard cholinesterase inhibitors, in individuals with mild or moderate dementia caused by Alzheimer's disease (AD).
authors.forename: Thekkuttuparambil Ananthanarayanan
authors.initials: TA
authors.lastname: Ajith
authors.forename: Nalin
authors.initials: N
authors.lastname: Nima
authors.forename: Ravindran Kalathil
authors.initials: RK
authors.lastname: Veena
authors.forename: Kainoor Krishnankutty
authors.initials: KK
authors.lastname: Janardhanan
authors.forename: Francis
authors.initials: F
authors.lastname: Antonawich
mesh_terms: D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004338:Drug Combinations; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010165:Palladium / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D004338:Drug Combinations; D010165:Palladium; D008063:Thioctic Acid; D013482:Superoxide Dismutase