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RAGE-Dependent Effect of Exogenous Methylglyoxal Intake on Lung Biomechanics in Mice
Samiya Al-Robaiy1,2, Alexander Navarrete Santos1, Andreas Simm1,2
1Center for Basic Medical Research (ZMG), University Hospital Halle (Saale), Martin Luther University Halle-Wittenberg, 06108 Halle (Saale), Germany.
Abstract:
Methylglyoxal (MG) is a known highly reactive dicarbonyl and precursor to free radicals and advanced glycation end-products (AGEs). It is discussed to be involved in tissue aging and in the pathogenesis of different degenerative diseases. The effect of long-term oral administration of MG, simulating dietary MG intake, on the lung biomechanics of wild type (WT) and receptor for advanced glycation end-products knockout (RAGE-KO) mice was studied using an ex vivo ventilation system starting at the age of 6 months and after feeding for 6 and 12 months with MG. Our results showed that MG was taken up in the circulation and efficiently excreted with urine. The amount of free urinary MG measured after 12 months of feeding was lowered. After 12 months feeding, a significant airway resistance increase accompanied by a decrease of the maximal inspiratory airflow was observed in WT animals. No effect of MG in lung function of RAGE-KO mice could be detected. Despite the evidence that MG entered the systemic circulation, no MG-derived AGE accumulation was detected in the lung lysates in dependency on MG-feeding. Our data indicate that the short-term feeding of MG has little effect in vivo. Only after long-term treatment was MG secretion reduced, leading to tissue impairment.
Insights
Long-term dietary methylglyoxal (MG) intake impaired lung function in wild-type mice by reducing MG excretion. Receptor for advanced glycation end-products (RAGE) knockout mice showed no such lung impairment from MG exposure.
Area of Science:
- Biochemistry
- Physiology
- Toxicology
Background:
- Methylglyoxal (MG) is a reactive dicarbonyl compound implicated in aging and degenerative diseases.
- MG is a precursor to advanced glycation end-products (AGEs), which can damage tissues.
Purpose of the Study:
- To investigate the effects of long-term oral methylglyoxal (MG) administration on lung biomechanics.
- To compare the impact of MG on wild-type (WT) and receptor for advanced glycation end-products knockout (RAGE-KO) mice.
Main Methods:
- Oral administration of MG to WT and RAGE-KO mice for 6 and 12 months.
- Ex vivo lung ventilation system to assess lung function (airway resistance, inspiratory airflow).
- Measurement of circulating and urinary MG levels, and lung AGE accumulation.
Main Results:
- MG was absorbed into circulation and excreted in urine, with reduced urinary MG after 12 months of feeding.
- WT mice showed increased airway resistance and decreased maximal inspiratory airflow after 12 months of MG feeding.
- RAGE-KO mice exhibited no significant changes in lung function due to MG exposure.
- No MG-derived AGE accumulation was detected in lung tissue despite MG circulation.
Conclusions:
- Long-term MG exposure impairs lung function in WT mice, linked to reduced MG excretion.
- The receptor for advanced glycation end-products (RAGE) pathway is crucial in mediating MG-induced lung tissue impairment.
- Short-term MG feeding has minimal in vivo effects, but chronic exposure can lead to detrimental outcomes.
