D-galactose-induced aging in rats - The effect of metformin on bioenergetics of brain, skeletal muscle and liver

被引：7

作者：

Sumbalova, Zuzana ^{[1
]}

Ulicna, Ol'ga ^{[1
]}

Kucharska, Jarmila ^{[1
]}

Rausova, Zuzana ^{[1
]}

Vancova, Ol'ga ^{[1
]}

Melichercik, L'ubomir ^{[2
,3
,4
]}

Tvrdik, Tomas ^{[2
,3
,4
]}

Nemec, Marek ^{[2
,5
]}

Kasparova, Svatava ^{[2
]}

机构：

[1] Comenius Univ, Fac Med, Pharmacobiochem Lab, Dept Internal Med 3, Sasinkova 4, Bratislava 81108, Slovakia

[2] Slovak Univ Technol Bratislava, Fac Chem & Food Technol, NMR & MS Lab, Cent Labs, Bratislava, Slovakia

[3] Comenius Univ, Slovak Med Univ, Fac Med, Dept Radiol, Bratislava, Slovakia

[4] Univ Hosp Bratislava, Bratislava, Slovakia

[5] EMPA Swiss Fed Labs Mat Sci & Technol, Bldg Energy Mat & Components Lab, Dubendorf, Switzerland

来源：

EXPERIMENTAL GERONTOLOGY | 2022年 / 163卷

关键词：

Aging; D-galactose model; Metformin; Mitochondria respiration; P-31; MRS; Coenzyme Q; COENZYME Q(10); MITOCHONDRIAL DYSFUNCTION; ALZHEIMERS-DISEASE; INSULIN-RESISTANCE; COGNITIVE FUNCTION; ENERGY-METABOLISM; MODEL; HEART; QUANTIFICATION; COMBINATION;

D O I：

10.1016/j.exger.2022.111770

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

Chronic D-galactose administration induces accelerated aging in rodents. The aim of the study was to find by in vivo P-31 MRS suitable markers of early stages of brain degeneration on this metabolic model in rats. Additionally, we studied the therapeutic effect of antidiabetic drug metformin. The study has been extended by in vitro determination of mitochondrial function in brain, skeletal muscle and liver mitochondria, oxidative stress parameter thiobarbituric acid reactive substances (TBARS), and lipophilic antioxidants levels. In vivo P-31 MRS revealed lower intracellular pH (pHi) and lower inorganic phosphate to ATP ratio (Pi/ATP), with higher index of oxidative phosphorylation - phosphocreatine (PCr) to Pi ratio - in brain of rats chronically administered with D-galactose. The function of brain mitochondria was not affected. Administration of metformin diminished changes in brain pHi and plasma TBARS. The function of skeletal muscle mitochondria and their coenzyme Q (CoQ) content were considerably reduced after D-galactose administration. Metformin administered simultaneously with D-galactose did not prevent these changes. The results of in vivo P-31 MRS revealed evidence of early stage of neurodegeneration that may indicate preinflammation. Our data show different susceptibility of brain, skeletal muscle, and liver to the chronic exposure to D-galactose and metformin. The D-galactose model presented in the literature as a model for "age-related dementia" had much more devastating effects on skeletal muscle than on the brain.

引用

页数：10

共 83 条

[21] Tightly coupled brain activity and cerebral ATP metabolic rate [J].