Metformin treatment in old rats and effects on mitochondrial integrity

2021 ◽  
Author(s):  
Allen Herbst ◽  
Austin Hoang ◽  
Chiye Kim ◽  
Judd Aiken ◽  
Debbie McKenzie ◽  
...  
Keyword(s):  
Metformin Treatment ◽  
Mitochondrial Integrity ◽  
Old Rats

Metformin reduces hyper-reactivity of platelets from patients with polycystic ovary syndrome by improving mitochondrial integrity

2015 ◽  
Vol 114 (09) ◽  
pp. 569-578 ◽  
Author(s):  
Amro Elgheznawy ◽  
Rüdiger Popp ◽  
Paul Rogowski ◽  
Imke Dornauf ◽  
Stefan Dröse ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Platelet Reactivity ◽  
Anion Channel ◽  
Metformin Treatment ◽  
Voltage Dependent Anion Channel ◽  
Ovary Syndrome ◽  
Mitochondrial Integrity ◽  
Increased Risk

SummaryPolycystic ovary syndrome (PCOS) is associated with decreased fertility, insulin resistance and an increased risk of developing cardiovascular disease. Treating PCOS patients with metformin improves fertility and decreases cardiovascular complications. Given that platelet activation contributes to both infertility and cardiovascular disease development, we assessed platelet reactivity in PCOS patients and the consequences of metformin treatment. Compared to washed platelets from healthy donors, platelets from PCOS patients demonstrated enhanced reactivity and impaired activation of the AMP-activated kinase (AMPK). PCOS platelets also demonstrated enhanced expression of mitochondrial proteins such as the cytochrome c reductase, ATP synthase and the voltage-dependent anion channel-1. However, mitochondrial function was impaired as demonstrated by a decreased respiration rate. In parallel, the phosphorylation of dynamin-related protein-1 (Drp-1) on Ser616 was increased while that on Ser637 decreased. The latter changes were accompanied by decreased mitochondrial size. In insulin-resistant PCOS patients (HOMA-IR> 2) metformin treatment (1.7 g per day for 4 weeks to 6 months) improved insulin sensitivity, restored mitochondrial integrity and function and normalised platelet aggregation. Treatment was without effect in PCOS patients with HOMA-IR< 2. Moreover, treatment of megakaryocytes with metformin enhanced mitochondrial content and in the same cells metformin enhanced the phosphorylation of the Drp-1 on Ser637 via an AMPK[uni03B1]1-dependent mechanism. In conclusion, the improvement of mitochondrial integrity and platelet reactivity may contribute to the beneficial effects of metformin on cardiovascular disease.

scholarly journals Metformin Preserves Mitochondrial Integrity at Old Age in Male Rats

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 690-690
Author(s):  
Jonathan Wanagat ◽  
Allen Herbst ◽  
Austin Hoang ◽  
Chiye Kim ◽  
Judd Aiken ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Copy Number ◽  
Male Rats ◽  
Metformin Treatment ◽  
Mtdna Copy Number ◽  
C Elegans ◽  
Mitochondrial Integrity ◽  
Mitochondrial Dna Copy Number ◽  
And Function ◽  
Deletion Frequency

Abstract Metformin is being deployed in clinical trials to ameliorate aging in older humans who do not have diabetes. In C. elegans, metformin treatment at old ages exacerbated mitochondrial dysfunction, led to respiratory failure, and shortened lifespan. Metformin is a commonly used, well-tolerated treatment for diabetes in older adults. Mitochondrial effects of metformin treatment in aged mammals has not been sufficiently investigated. We hypothesized that metformin treatment would not be toxic to older mammals. To define a therapeutic dose in aged hybrid rats, we evaluated two doses of metformin (0.1%, 0.75% of the diet) at 30-months of age. Body mass decreased at the 0.75% dose. Neither dose affected mortality between 30- and 34-months of age. We assessed mitochondrial quality, quantity, and function in aged rats treated with metformin at the 0.75% dose by measuring mitochondrial DNA copy number, deletion mutation frequency, and respirometry in skeletal muscle and heart. In skeletal muscle, we observed no effect of metformin on quadriceps mass, mtDNA copy number or deletion frequency. In the heart, metformin treated rats had higher mtDNA copy number, lower cardiac mass and no effect on deletion frequency. Metformin treatment resulted in lower mitochondrial complex I activity in both heart and quadriceps. Metformin did not compromise mitochondrial integrity, was well tolerated, and may have cardiac benefits to rats at old ages.

Endotoxin Alteration of the Mucopolysaccharide Blood Vessel Coating in Rats

1974 ◽  
Vol 32 ◽  
pp. 148-149
Author(s):  
D. E. Philpott ◽  
A. Takahashi
Keyword(s):  
Skeletal Muscle ◽  
Endothelial Cells ◽  
Salivary Gland ◽  
Carotid Artery ◽  
Basement Membrane ◽  
Coronary Vessels ◽  
Ruthenium Red ◽  
E Coli ◽  
Old Rats ◽  
The Brain

Two month, eight month and two year old rats were treated with 10 or 20 mg/kg of E. Coli endotoxin I. P. The eight month old rats proved most resistant to the endotoxin. During fixation the aorta, carotid artery, basil arartery of the brain, coronary vessels of the heart, inner surfaces of the heart chambers, heart and skeletal muscle, lung, liver, kidney, spleen, brain, retina, trachae, intestine, salivary gland, adrenal gland and gingiva were treated with ruthenium red or alcian blue to preserve the mucopolysaccharide (MPS) coating. Five, 8 and 24 hrs of endotoxin treatment produced increasingly marked capillary damage, disappearance of the MPS coating, edema, destruction of endothelial cells and damage to the basement membrane in the liver, kidney and lung.

Light and electron microscopic investigation of adenohypophyses of germfree, food-restricted, and germfree-food restricted aging, male lobund-wistar rats

1988 ◽  
Vol 46 ◽  
pp. 352-353
Author(s):  
G. Ilse ◽  
K. Kovacs ◽  
N. Ryan ◽  
T. Sano ◽  
L. Stefaneanu ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Microscopic Investigation ◽  
Electron Microscopic Investigation ◽  
Aging Male ◽  
Sprague Dawley ◽  
Electron Microscopic ◽  
Sprague Dawley Rats ◽  
Old Rats ◽  
Ad Libitum ◽  
Microscopic Findings

Germfree state and food restriction have been shown to increase life span and delay tumor occurrence in rats. We report here the histologic, immunocytochemical and electron microscopic findings of adenohypophyses of aging, male Lobund-Wistar rats raised at Lobund Laboratories. In our previous study, the morphologic changes in the adenohypophyses of old rats have been extensively investigated by histology, immunocytochemistry and electron microscopy. Lactotroph adenomas were frequent in Long-Evans and Sprague-Dawley rats, whereas gonadotroph adenomas were frequent in Sprague-Dawley and Wistar rats.Male Lobund-Wistar rats were divided into four groups: 1) conventional, which were raised under normal non-germfree environment and received food ad libitum; 2) germfree-food ad libitum; 3) conventional environment-food restricted and 4) germfree-food restricted. The adenohypophyses were removed from 6-month-, 18-month- and 30-month-old rats. For light microscopy, adenohypophyses were fixed in formalin and embedded in paraffin.

A Comparison of the Ultrastructural Morphology of Hepatic Necrosis in BDF1 Mice

1981 ◽  
Vol 39 ◽  
pp. 586-587
Author(s):  
Becky Jackson
Keyword(s):  
Endoplasmic Reticulum ◽  
Smooth Endoplasmic Reticulum ◽  
Preliminary Investigation ◽  
Hepatic Necrosis ◽  
Hepatic Tissue ◽  
Pronounced Increase ◽  
Glycogen Store ◽  
Ultrastructural Morphology ◽  
Mitochondrial Integrity ◽  
Glycogen Stores

Preliminary investigation has indicated similarity in hepatic ultrastructural morphology in nutritional deprivation, and cyanide induced hepatic necrosis. Analysis of hepatic tissue has indicated disruption of intracellular membranes, specifically, reduction in rough endoplasmic reticulum (RER) mitochondrial integrity, and glycogen stores. An increase in smooth endoplasmic reticulum (SER) portion was observed.To further investigate the apparent equivalence of necrotic morphology, ultrastructura1ly, BDF1 mice were subjected to senescence, nutritional deprevation, potassium cyanide (KCN) induced toxemia, and acetaminophen induced toxemia. Controls were utilized to ellucidate non-necrotic hepatocellular normals. U1trastructura1 investigation of controls (Fig. 1) shows densely granular RER, abundant glycogen stores, and morphologically normal mitochondria. Subjects with acetaminophen induced necrosis exhibit reduced normal RER with increased levels of dialated, vesicular RER in apparent conversion to SER (Fig. 2), loss of mitochondrial integrity, and glycogen store reduction. Senescent subjects exhibit a pronounced increase in SER and loss of glycogen store. (Fig. 3). Investigation of the senescent SER at high magnification (Fig. 5) indicates that the SER is arising from degranulating and vesiculating RER.

Metformin treatment during cardiac pressure overload does not improve survival

2014 ◽  
Vol 62 (S 01) ◽  
Author(s):  
A. Schrepper ◽  
M. Schwarzer ◽  
R. Dormann ◽  
C. Werner ◽  
T. Doenst
Keyword(s):  
Pressure Overload ◽  
Metformin Treatment

Metformin Treatment Ameliorates Liver Injury Indicating Fatty Liver Polycystic Ovary Syndrome

2015 ◽  
Vol 53 (01) ◽  
Author(s):  
S Tan ◽  
N Vollmar ◽  
S Benson ◽  
LP Bechmann ◽  
G Gerken ◽  
...  
Keyword(s):  
Liver Injury ◽  
Polycystic Ovary Syndrome ◽  
Fatty Liver ◽  
Polycystic Ovary ◽  
Metformin Treatment ◽  
Ovary Syndrome

Autoradiography of Incorporated Leucine-H3 in the Enamel Matrix and Enamel Organ of the Upper Incisor of the Rat

1964 ◽  
Vol 04 (02) ◽  
pp. 186-192
Author(s):  
Leonel Costacurta
Keyword(s):  
Amino Acid ◽  
Blood Vessels ◽  
Tooth Germ ◽  
Longitudinal Section ◽  
Equal Length ◽  
Enamel Organ ◽  
Enamel Matrix ◽  
Distal Extremity ◽  
Old Rats ◽  
Thin Band

SummaryDental germs of the upper incisors of six-days old rats were studied for the uptake of leucine-H3 by different layers of the enamel organ in correlation to the various stages of the development of enamel.The longitudinal section of the tooth germ was divided into 15 zones of about equal length in order to facilitate the description and interpretation of results. Autoradiographic images of the histologic preparations from rats sacrificed 30 minutes, 1 hour, 1 day and 3 days after the injection were made. The strongest reactions were observed in dental germs of rats sacrificed 1 hour, and particularly one day, after the leucine-H3 injection.The uptake of this compound by the enamel matrix increases progressively up to the young enamel and then decreases to the distal extremity; the greatest quantity of this labeled amino-acid was observed in the primary and young enamel. The reactions were present in the transitional enamel only along a thin band close to the dentine-enamel junction.In the enamel organ leucine-H3 incorporation was greatest in the three layers, the zones corresponding to primary and young enamel. In zones corresponding to transitional enamel, the inner epithelium showed a small quantity, and the stellate reticulum a blackening only in its superficial part, were the blood vessels reach the enamel organ.

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