Abstract
The relationship between the potentially developing complications of the 451 million people affected by diabetes and hyperglycaemia can be based on the enhanced generation of advanced glycation endproducts and the more intensive oxidative and carbonyl stress. Advanced glycation endproducts generated partly due to carbonyl stress play an important role in the pathogenesis of diabetic complications such as elevated arterial thickness, vascular permeability, enhanced angiogenesis or the more rigid vessels induced nephropathy, neuropathy, retinopathy. Furthermore, the elevated thrombocyte aggregation, the reduced fibrinolysis induced elevated coagulation, and the atherosclerosis or the mitochondrial dysfunction are important as well. The most potent target of both the non-oxidative and oxidative generation of advanced glycation endproducts can be the scavenging of α,β-unsaturated aldehydes. Although, aminoguanidine, the prototype of scavenger molecules, showed protection in different animal models, it failed in the human clinical studies. Finally, the clinical studies were terminated almost 20 years ago. The endogen dipeptide L-carnosine was also expected to mitigate the complications due to carbonyl stress. However, its clinical significance was limited by the serum carnosinases and by the consequent low serum stability and bioavailability. The carnosinase resistance of the molecule can be achieved by the change of the carboxyl group of the molecule to hydroxyl group. At the same time, the biosafety and the carbonyl stress scavenging activity of the molecule could be preserved. Although clinical studies could not be performed in the last six months, on the basis of the in vitro and in vivo results, carnosinole seems to be a promising compound to mitigate and prevent the diabetic complications. Thus it is worth to the attention of the clinicians. Orv Hetil. 2019; 160(40): 1567-1573.
Highlights
The relationship between the potentially developing complications of the 451 million people affected by diabetes and hyperglycaemia can be based on the enhanced generation of advanced glycation endproducts and the more intensive oxidative and carbonyl stress
Advanced glycation endproducts generated partly due to carbonyl stress play an important role in the pathogenesis of diabetic complications such as elevated arterial thickness, vascular permeability, enhanced angiogenesis or the more rigid vessels induced nephropathy, neuropathy, retinopathy
The most potent target of both the non-oxidative and oxidative generation of advanced glycation endproducts can be the scavenging of α,β-unsaturated aldehydes
Summary
A 2017-ben mintegy 451 millió, diabetesben szenvedő emberben potenciálisan kialakuló hosszú távú szövődmények és a hyperglykaemia között fennálló kapcsolatot a nagyobb mértékben keletkező késői glikációs végtermékek, valamint a fokozott oxidatív és karbonilstressz jelentheti. A részben karbonilstressz révén keletkező késői glikációs végtermékek szerepét olyan szövődményekben írták le, mint az érfalvastagodás, a megnövekedett érfal-áteresztőképesség, a fokozott mértékű angiogenezis vagy a csökkent érfalrugalmasság okozta nephropathia, neuropathia, retinop athia. Sajnálatos módon a befogó molekulák prototípusát jelentő aminoguanidin, bár különböző állatmodelleken sikeresnek bizonyult, a klinikai teszteken nem bizonyított, a vele kapcsolatos klinikai vizsgálatokat közel 20 évvel ezelőtt leállították. Bár a karnozinol kifejlesztése óta eltelt mindössze fél év nem tette lehetővé, hogy klinikai teszteken bizonyítson, a molekulával kapcsolatban elért in vitro és in vivo eredmények alapján ígéretes hatóanyagnak tűnik a diabetes szövődményeinek mérséklésére, megelőzésére, így a klinikusnak is érdemes nyomon követni a vele kapcsolatos híreket, eredményeket.
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