Diabetic Neuropathy - Treatment

Carnosine - updated: 15 March 2008

Pluripotent protective effects of carnosine, a naturally occurring dipeptide

Ann N Y Acad Sci. 1998 Nov 20;854:37-53

Hipkiss AR, Preston JE, Himsworth DT, Worthington VC, Keown M, Michaelis J, Lawrence J, Mateen A, Allende L, Eagles PA, Abbott NJ

Carnosine is a naturally occurring dipeptide (beta-alanyl-L-histidine) found in brain, innervated tissues, and the lens at concentrations up to 20 mM in humans. In 1994 it was shown that carnosine could delay senescence of cultured human fibroblasts. Evidence will be presented to suggest that carnosine, in addition to antioxidant and oxygen free-radical scavenging activities, also reacts with deleterious aldehydes to protect susceptible macromolecules. Our studies show that, in vitro, carnosine inhibits nonenzymic glycosylation and cross-linking of proteins induced by reactive aldehydes (aldose and ketose sugars, certain triose glycolytic intermediates and malondialdehyde (MDA), a lipid peroxidation product). Additionally we show that carnosine inhibits formation of MDA-induced protein-associated advanced glycosylation end products (AGEs) and formation of DNA-protein cross-links induced by acetaldehyde and formaldehyde. At the cellular level 20 mM carnosine protected cultured human fibroblasts and lymphocytes, CHO cells, and cultured rat brain endothelial cells against the toxic effects of formaldehyde, acetaldehyde and MDA, and AGEs formed by a lysine/deoxyribose mixture. Interestingly, carnosine protected cultured rat brain endothelial cells against amyloid peptide toxicity. We propose that carnosine (which is remarkably nontoxic) or related structures should be explored for possible intervention in pathologies that involve deleterious aldehydes, for example, secondary diabetic complications, inflammatory phenomena, alcoholic liver disease, and possibly Alzheimer's disease.

A possible new role for the anti-ageing peptide carnosine

Cell Mol Life Sci. 2000 May;57(5):747-53

Hipkiss AR, Brownson C.

The naturally occurring dipeptide carnosine (beta-alanyl-L-histidine) is found in surprisingly large amounts in long-lived tissues and can delay ageing in cultured human fibroblasts. Carnosine has been regarded largely as an anti-oxidant and free radical scavenger. More recently, an anti-glycating potential has been discovered whereby carnosine can react with low-molecular-weight compounds that bear carbonyl groups (aldehydes and ketones). Carbonyl groups, arising mostly from the attack of reactive oxygen species and low-molecular-weight aldehydes and ketones, accumulate on proteins during ageing. Here we propose, with supporting evidence, that carnosine can react with protein carbonyl groups to produce protein-carbonyl-carnosine adducts ('carnosinylated' proteins). The various possible cellular fates of the carnosinylated proteins are discussed. These proposals may help explain anti-ageing actions of carnosine and its presence in non-mitotic cells of long-lived mammals.

Publication Types:

• Review

Carnosine: a versatile antioxidant and antiglycating agent

Sci Aging Knowledge Environ. 2005 May 4;2005(18):pe12

Reddy VP, Garrett MR, Perry G, Smith MA.

Carnosine (beta-alanyl-L-histidine) has recently attracted much attention as a naturally occurring antioxidant and transition-metal ion sequestering agent. It has also been shown to act as an anti-glycating agent, inhibiting the formation of advanced glycation end products (AGEs). Through its distinctive combination of antioxidant and antiglycating properties, carnosine is able to attenuate cellular oxidative stress and can inhibit the intracellular formation of reactive oxygen species and reactive nitrogen species. By controlling oxidative stress, suppressing glycation, and chelating metal ions, carnosine is able to reduce harmful sequelae such as DNA damage. AGEs are known contributors to the pathology of Alzheimer's disease, and carnosine therefore merits serious attention as a possible therapeutic agent.

Publication Types:

• Review

Carnosine--biological activity and perspectives in pharmacotherapy

Wiad Lek. 2007;60(1-2):73-9

Zieba R.

This review summarizes the data on biological activity and therapeutic potential of camosine. Camosine is a naturally occurring, water-soluble dipeptide. It has buffering activities in excitable animal and human tissues, exhibits metal ions binding properties, antioxidant and antiglycating properties, extends the life-span of cultured human diploid cells, regulates sarcoplasmic reticulum Ca-release channel activity. Carnosine may be a potential therapeutic agent (neurodegenerative, metabolic

Publication Types:

• Review

Antiglycation and antioxidant effect of carnosine against glucose degradation products in peritoneal mesothelial cells

Nephron Clin Pract. 2007;107(1):c26-34. Epub 2007 Jul 24

Alhamdani MS, Al-Kassir AH, Abbas FK, Jaleel NA, Al-Taee MF.

BACKGROUND/AIM:Toxicity with advanced glycation end products (AGEs) is a major problem in uremic patients. Treatment with peritoneal dialysis (PD) exacerbates AGE formation as a result of bioincompatibility of the conventional peritoneal dialysis fluid (PDF). The presence of glucose degradation products (GDPs) in PDF is the main cause of its bioincompatibility. Carnosine is an endogenous dipeptide with a powerful antiglycation/antioxidant activity. In an attempt to improve PDF biocompatibility, we evaluated the effect of carnosine in human peritoneal mesothelial cells (HPMC) incubated with PDF or GDPs in vitro. METHODS: HPMC were incubated for short or prolonged time with PDF in the presence or absence of carnosine. Similarly, HPMC were incubated in the same condition but with a combination of GDPs. Following the incubation, cells were tested for their viability, protein carbonyl content and reactive oxygen species (ROS) production. RESULTS: Results demonstrated a significant protective effect of carnosine to HPMC in both acute and chronic conditions with PDF or GDPs as judged by the enhancement of cell viability, preserved protein from modification and decreased ROS production. CONCLUSION: Carnosine enhanced HPMC viability against the toxic effect of GDPs probably through protection of cellular protein from modification and from ROS-mediated oxidative damage. The salutary effect of carnosine may render it a desirable candidate for improving PDF biocompatibility and reducing AGE complications in PD patients.

Publication Types:

• Review