Carnosine Articles 1

© 2011

N-Acetylcarnosine sustained drug delivery eye drops to control the signs of ageless vision: glare sensitivity, cataract amelioration and quality of vision currently available treatment for the challenging 50,000-patient population

            (Babizhayev, Burke et al. 2009) Download

BACKGROUND: Innovative Vision Products, Inc. (IVP)'s scientists developed the lubricant eye drops (Can-C) designed as 1% N-acetylcarnosine (NAC) prodrug of L-carnosine containing a mucoadhesive cellulose-based compound combined with corneal absorption promoters in a sustained drug delivery system. Only the natural L-isomeric form of NAC raw material was specifically synthesized at the cGMP facility and employed for the manufacturing of Can-C eye drops. OBJECTIVE AND STUDY DESIGN: In the present clinical study the authors assessed vision before and after 9 month term of topical ocular administration of NAC lubricant eye drops or placebo in 75 symptomatic patients with age-related uncomplicated cataracts in one or both eyes, with acuity in one eye of 20/40 or worse (best-corrected distance), and no previous cataract surgery in either eye and no other ocular abnormality and 72 noncataract subjects ranged in age from 54 to 78 years. SETTING: Subjects in these subsample groups have reported complaints of glare and wanted to administer eye drops to get quick eye relief and quality of vision for their daily activities including driving and computer works. Following 9 months of treatment with NAC lubricant eye drops, most patients' glare scores were improved or returned to normal in disability glare tests with Halometer DG. Improvement in disability glare was accompanied with independent improvement in acuity. Furthermore, patients with the poorest pretreatment vision were as likely to regain certain better visual function after 9 months of treatment with N-acetylcarnosine lubricant eye drops as those with the worth pretreatment vision. PATIENTS OR OTHER PARTICIPANTS: The authors made a reference to electronic records of the product sales to patients who have been made the repurchase of the Can-C eye drops since December 2001. INTERVENTION: Based on this analysis of recorded adjustments to inventory, various parameters were analyzed during the continued repurchase behavior program, including testimonials from buyers. With these figures, researchers judged on the patients' compliance rate to self-administer NAC eye-drops. MAIN OUTCOME MEASURE AND RESULTS: The ophthalmic drug showed potential for the non-surgical treatment of age-related cataracts for participants after controlling for age, gender and daily activities and on a combined basis of repurchases behavior reports in more than 50,000 various cohort survivors, has been demonstrated to have a high efficacy and good tolerability for prevention and treatment of visual impairment determined for the older population with relative stable pattern of causes for blindness and visual impairment. The mechanisms of prevention and reversal of cataracts with NAC ophthalmic drug are considered which include prevention by the intraocular released carnosine of free-radical-induced inactivation of proprietary lens antioxidant enzymes (superoxide dismutase); prevention of carbohydrate and metal-catalyzed autooxidation of ascorbic acid-induced cross-linking glycation reactions to the lens proteins; transglycation properties of carnosine, allowing it to compete for the glycating agent, protecting proteins (lens crystallins) against modification; universal antioxidant and scavenging activity towards lipid hydroperoxides, aldehydes and oxygen radicals; activation with l-carnosine ingredient of proteasome activity in the lens; chaperone-like disaggregating to lens crystallins activity of NAC and of its bioactivated principal carnosine. Blindness incidence increased with advancing age, such as cataract and glaucoma, which are by far the commonest causes of blindness in our sample and in all age groups, glaucomatous neurodegeneration can be treated with developed NAC autoinduction prodrug eye drops equipped with corneal absorption promoters. The common blinding affections presenting in developed countries such as, senile macular degeneration, hereditary chorioretinal dystrophies, diabetic retinopathy are poorly represented in our current summary of vital-statistics and will be reported inherent in next N-acetylcarnosine ophthalmic drug studies. CONCLUSION: The authors present evidence, about why only a certain kind of NAC is safe, and why only certain formulas designed by IVP for drug discovery are efficacious in the prevention and treatment of senile cataract for long-term use. Overall cumulated studies demonstrate that the designed by IVP new vision-saving drug NAC eye drops help the aging eye to recover by improving its clarity, glare sensitivity, color perception and overall vision.

Brain type carnosinase in dementia: a pilot study

            (Balion, Benson et al. 2007) Download

BACKGROUND: The pathological processes underlying dementia are poorly understood and so are the markers which identify them. Carnosinase is a dipeptidase found almost exclusively in brain and serum. Carnosinase and its substrate carnosine have been linked to neuropathophysiological processes. METHODS: Carnosinase activity was measured by a flourometric method in 37 patients attending a Geriatric Outpatient Clinic. There were 17 patients without dementia, 13 had Alzheimer's disease (AD) and 7 had mixed dementia (MD). RESULTS: The range of serum carnosinase activity for patients without dementia was 14.5 - 78.5 micromol/ml/h. There was no difference in carnosinase activity between patients without dementia (40.3 +/- 15.2 micromol/ml/h) and patients with AD (44.4 +/- 12.4 micromol/ml/h) or MD (26.6 +/- 15 micromol/ml/h). However, levels in the MD group were significantly lower than the AD group (p = 0.01). This difference remained significant after adjusting for gender, MMSE score, exercise, but not age, one at a time and all combined. The effect of other medical conditions did not remove the significance between the AD and MD groups. The MD group, but not the AD group, demonstrated a significant trend with carnosinase activity decreasing with duration of disease (from first recorded date of diagnosis to date of blood collection) (r = -0.76, p = 0.049). There was no association with carnosinase activity and MMSE score in the AD or MD group. Both AD and MD patients on any dementia medication (donepezil, galantamine, memantine) had higher carnosinase activity compared to those not taking a dementia medication. Carnosinase activity was higher in patients who regularly exercised (n = 20) compared to those who did not exercise regularly (n = 17)(p = 0.006). CONCLUSION: This exploratory study has shown altered activities of the enzyme carnosinase in patients with dementia.

Effects of dietary supplementation of carnosine on mitochondrial dysfunction, amyloid pathology, and cognitive deficits in 3xTg-AD mice

            (Corona, Frazzini et al. 2011) Download

BACKGROUND: The pathogenic road map leading to Alzheimer's disease (AD) is still not completely understood; however, a large body of studies in the last few years supports the idea that beside the classic hallmarks of the disease, namely the accumulation of amyloid-beta (Abeta) and neurofibrillary tangles, other factors significantly contribute to the initiation and the progression of the disease. Among them, mitochondria failure, an unbalanced neuronal redox state, and the dyshomeostasis of endogenous metals like copper, iron, and zinc have all been reported to play an important role in exacerbating AD pathology. Given these factors, the endogenous peptide carnosine may be potentially beneficial in the treatment of AD because of its free-radical scavenger and metal chelating properties. METHODOLOGY: In this study, we explored the effect of L-carnosine supplementation in the 3xTg-AD mouse, an animal model of AD that shows both Abeta- and tau-dependent pathology. PRINCIPAL FINDINGS: We found that carnosine supplementation in 3xTg-AD mice promotes a strong reduction in the hippocampal intraneuronal accumulation of Abeta and completely rescues AD and aging-related mitochondrial dysfunctions. No effects were found on tau pathology and we only observed a trend toward the amelioration of cognitive deficits. CONCLUSIONS AND SIGNIFICANCE: Our data indicate that carnosine can be part of a combined therapeutic approach for the treatment of AD.


Carnosine, diabetes and Alzheimer's disease

            (Hipkiss 2009) Download

Aging, Proteotoxicity, Mitochondria, Glycation, NAD and Carnosine: Possible Inter-Relationships and Resolution of the Oxygen Paradox

            (Hipkiss 2010) Download

It is suggested that NAD(+) availability strongly affects cellular aging and organism lifespan: low NAD(+) availability increases intracellular levels of glycolytic triose phosphates (glyceraldehyde-3-phosphate and dihydroxyacetone-phosphate) which, if not further metabolized, decompose spontaneously into methylglyoxal (MG), a glycating agent and source of protein and mitochondrial dysfunction and reactive oxygen species (ROS). MG-damaged proteins and other aberrant polypeptides can induce ROS generation, promote mitochondrial dysfunction and inhibit proteasomal activity. Upregulation of mitogenesis and mitochondrial activity by increased aerobic exercise, or dietary manipulation, helps to maintain NAD(+)availability and thereby decreases MG-induced proteotoxicity. These proposals can explain the apparent paradox whereby aging is seemingly caused by increased ROS-mediated macromolecular damage but is ameliorated by increased aerobic activity. It is also suggested that increasing mitochondrial activity decreases ROS generation, while excess numbers of inactive mitochondria are deleterious due to increased ROS generation. The muscle- and brain-associated dipeptide, carnosine, is an intracellular buffer which can delay senescence in cultured human fibroblasts and delay aging in senescence-accelerated mice. Carnosine's ability to react with MG and possibly other deleterious carbonyl compounds, and scavenge various ROS, may account for its protective ability towards ischemia and ageing.

Inhibition of the growth of transformed and neoplastic cells by the dipeptide carnosine

            (Holliday and McFarland 1996) Download

Human diploid fibroblasts growth normally in medium containing physiological concentrations of the naturally occurring dipeptide carnosine (beta-alanyl-L-histidine). These concentrations are cytotoxic to transformed and neoplastic cells lines in modified Eagle medium (MEM), whereas these cells grow vigorously in Dulbecco's modified Eagle medium (DMEM) containing carnosine. This difference is due to the presence of 1 mM sodium pyruvate in DMEM. Seven human cell lines and two rodent cell lines were tested and all are strongly inhibited by carnosine in the absence of pyruvate. Experiments with HeLa cells show that anserine is similar to carnosine, but D-carnosine and homocarnosine are without effect. Also, the non-essential amino acids alanine and glutamic acid contribute to the effect of pyruvate in preventing carnosine toxicity, and oxaloacetate and alpha-ketoglutarate can substitute for pyruvate. We have used mixtures of normal MRC-5 fibroblasts and HeLa cells to demonstrate that 20 mM carnosine can selectively eliminate the tumour cells. This has obvious implications which might be exploited in in vivo and in vitro studies. Carnosine is known to react strongly with aldehyde and keto groups of sugars by Amadori reaction, and we propose that it depletes certain glycolysis intermediates. It is well known that tumour cells are more dependent on glycolysis than normal cells. A reduction of glycolysis intermediates by carnosine may deplete their energy supply, but this effect is totally reversed by pyruvate.

Carnosine as a protective factor in diabetic nephropathy: association with a leucine repeat of the carnosinase gene CNDP1

            (Janssen, Hohenadel et al. 2005) Download

The risk of diabetic nephropathy is partially genetically determined. Diabetic nephropathy is linked to a gene locus on chromosome 18q22.3-q23. We aimed to identify the causative gene on chromosome 18 and to study the mechanism by which the product of this gene could be involved in the development of diabetic nephropathy. DNA polymorphisms were determined in 135 case (diabetic nephropathy) and 107 control (diabetes without nephropathy) subjects. The effect of carnosine on the production of extracellular matrix components and transforming growth factor-beta (TGF-beta) after exposure to 5 and 25 mmol/l d-glucose was studied in cultured human podocytes and mesangial cells, respectively. A trinucleotide repeat in exon 2 of the CNDP1 gene, coding for a leucine repeat in the leader peptide of the carnosinase-1 precursor, was associated with nephropathy. The shortest allelic form (CNDP1 Mannheim) was more common in the absence of nephropathy (P = 0.0028, odds ratio 2.56 [95% CI 1.36-4.84]) and was associated with lower serum carnosinase levels. Carnosine inhibited the increased production of fibronectin and collagen type VI in podocytes and the increased production of TGF-beta in mesangial cells induced by 25 mmol/l glucose. Diabetic patients with the CNDP1 Mannheim variant are less susceptible for nephropathy. Carnosine protects against the adverse effects of high glucose levels on renal cells.

Applicability of zinc complex of L-carnosine for medical use

            (Matsukura and Tanaka 2000) Download

Zinc complex of L-carnosine (L-CAZ; generic name Polaprezinc) is the first drug for oral administration in which zinc plays an essential role. L-CAZ was approved as an anti-ulcer drug of membrane protection type. Characterization of L-CAZ was achieved by various spectroscopic methods along with elemental analysis. Zinc ion coordinates with L-carnosine to form a quadridentate 1:1 complex of polymeric nature in order to maintain low strain of chelate rings. L-CAZ can remain in stomach juice without rapid dissociation and adhere to ulcerous lesion specifically, after which L-carnosine and zinc are released to heal the ulcer. L-CAZ exhibited high efficacy in clinical use without any serious side effect. L-CAZ exhibited an inhibitory effect on Helicobacter pylori. Physicochemical aspects on carnosine, zinc, and zinc complex can explain favorable features of L-CAZ as a drug.

Protection by polaprezinc against radiation-induced apoptosis in rat jejunal crypt cells

            (Matsuu-Matsuyama, Shichijo et al. 2008) Download

Polaprezinc, an anti-ulcer drug, is a chelate compound consisting of zinc and L-carnosine. Polaprezinc has been shown to prevent gastric mucosal injury. The anti ulcer effects of polaprezinc have been ascribed to its antioxidative property. The effect of polaprezinc on ionizing radiation-induced apoptosis was studied in the jejunal epithelial crypt cells of rats. Seven-to eight week-old Wistar rats, which were treated with 100 mg/kg of polaprezinc orally 1h before irradiation or 2% carboxymethyl cellulose sodium in controls, were exposed to whole body X-ray irradiation at 2 Gy. The number of apoptotic cells per jejunum crypt was counted in haematoxylin and eosin stained sections at 0-6 h after irradiation. TUNEL positive cells and immunopositive cells for active caspase-3 per crypt were also counted. Accumulation of p53, p21(WAF1/CIP1) and Bax expression in the jejunum after irradiation were examined by Western blot analyses. Polaprezinc treatment given prior to radiation resulted in a significant reduction in numbers of apoptotic cells, TUNEL positive cells and active caspase-3 immunopositive cells in jejunal crypt cells. Polaprezinc treatment resulted in decreases of p53 accumulation, p21(WAF1/CIP1) and Bax expression after irradiation. Polaprezinc has a protective effect against ionizing radiation induced apoptosis in rat jejunal crypt cells.

Differential neuroprotective effects of carnosine, anserine, and N-acetyl carnosine against permanent focal ischemia

            (Min, Senut et al. 2008) Download

Carnosine (beta-alanyl-L-histidine) has been shown to exhibit neuroprotection in rodent models of cerebral ischemia. In the present study, we further characterized the effects of carnosine treatment in a mouse model of permanent focal cerebral ischemia and compared them with its related peptides anserine and N-acetylated carnosine. We also evaluated the efficacy of bestatin, a carnosinase inhibitor, in ameliorating ischemic brain damage. Permanent focal cerebral ischemia was induced by occlusion of the middle cerebral artery (pMCAO). Mice were subsequently randomly assigned to receive an intraperitoneal injection of vehicle (0.9% saline), carnosine, N-acetyl carnosine, anserine, bestatin alone, or bestatin with carnosine. Infarct size was examined using 2,3,5-triphenyltetrazolium chloride staining 1, 3, and 7 days following pMCAO, and neurological function was evaluated using an 18-point-based scale. Brain levels of carnosine were measured in treated mice using high-performance liquid chromatography 1 day following pMCAO. We demonstrated that treatment with carnosine, but not its analogues, was able to significantly reduce infarct volume and improve neurological function compared with those in vehicle-treated mice. These beneficial effects were maintained for 7 days post-pMCAO. In contrast, compared with the vehicle-treated group, bestatin-treated mice displayed an increase in the severity of ischemic lesion, which was prevented by the addition of carnosine. These new data further characterize the neuroprotective effects of carnosine and suggest that carnosine may be an attractive candidate for testing as a stroke therapy.

Polaprezinc Protects Mice against Endotoxin Shock

            (Ohata, Moriyama et al. 2010) Download

Polaprezinc (PZ), a chelate compound consisting of zinc and l-carnosine (Car), is an anti-ulcer drug developed in Japan. In the present study, we investigated whether PZ suppresses mortality, pulmonary inflammation, and plasma nitric oxide (NO) and tumor necrosis factor (TNF)-alpha levels in endotoxin shock mice after peritoneal injection of lipopolysaccharide (LPS), and how PZ protects against LPS-induced endotoxin shock. PZ pretreatment inhibited the decrease in the survival rate of mice after LPS injection. PZ inhibited the increases in plasma NO as well as TNF-alpha after LPS. Compatibly, PZ suppressed LPS-induced inducible NO synthase mRNA transcription in the mouse lungs. PZ also improved LPS-induced lung injury. However, PZ did not enhance the induction of heat shock protein (HSP) 70 in the mouse lungs after LPS. Pretreatment of RAW264 cells with PZ suppressed the production of NO and TNF-alpha after LPS addition. This inhibition likely resulted from the inhibitory effect of PZ on LPS-mediated nuclear factor-kappaB (NF-kappaB) activation. Zinc sulfate, but not Car, suppressed NO production after LPS. These results indicate that PZ, in particular its zinc subcomponent, inhibits LPS-induced endotoxin shock via the inhibition of NF-kappaB activation and subsequent induction of proinflammatory products such as NO and TNF-alpha, but not HSP induction.

Carnosine retards tumor growth in vivo in an NIH3T3-HER2/neu mouse model

            (Renner, Zemitzsch et al. 2010) Download

BACKGROUND: It was previously demonstrated that the dipeptide carnosine inhibits growth of cultured cells isolated from patients with malignant glioma. In the present work we investigated whether carnosine also affects tumor growth in vivo and may therefore be considered for human cancer therapy. RESULTS: A mouse model was used to investigate whether tumor growth in vivo can be inhibited by carnosine. Therefore, NIH3T3 fibroblasts, conditionally expressing the human epidermal growth factor receptor 2 (HER2/neu), were implanted into the dorsal skin of nude mice, and tumor growth in treated animals was compared to control mice. In two independent experiments nude mice that received tumor cells received a daily intra peritoneal injection of 500 microl of 1 M carnosine solution. Measurable tumors were detected 12 days after injection. Aggressive tumor growth in control animals, that received a daily intra peritoneal injection of NaCl solution started at day 16 whereas aggressive growth in mice treated with carnosine was delayed, starting around day 19. A significant effect of carnosine on tumor growth was observed up to day 24. Although carnosine was not able to completely prevent tumor growth, a microscopic examination of tumors revealed that those from carnosine treated animals had a significant lower number of mitosis (p < 0.0003) than untreated animals, confirming that carnosine affects proliferation in vivo. CONCLUSION: As a naturally occurring substance with a high potential to inhibit growth of malignant cells in vivo, carnosine should be considered as a potential anti-cancer drug. Further experiments should be performed in order to understand how carnosine acts at the molecular level.

Effect of a combination of carnosine and aspirin eye drops on streptozotocin -- induced diabetic cataract in rats

            (Shi, Yan et al. 2009) Download

PURPOSE: To investigate the effect of a combination of carnosine and aspirin eye drops on the progression of diabetic cataract formation induced by streptozotocin (STZ). METHODS: Rats were made diabetic with STZ. Animals in the treated groups received carnosine, aspirin, or a combination of carnosine and aspirin as drops to the eyes. Cataract progression was monitored by slit lamp microscope and classified into four stages. At the end of 8 weeks, the animals were killed and biochemical changes were determined. Blood and urine glucose levels, body weights, food, and intake were also determined. RESULTS: About 84.4% of the rats responded to the STZ injection. There were statistically significant differences in the stage of cataract of lenses between the untreated and the treated diabetic animals and between the combination and the aspirin group at the 7th and 8th week. There was a significant decrease in the water-soluble protein in the diabetic groups compared with the control group. The three treatments improved the water-soluble protein levels, and the combination treatment had the greatest effect. The levels of thiol were remarkably decreased in the lenses of diabetic rats, except the combination group. The specific activity of glutathione peroxidase (GPx) was increased and the activities of glutathione reductase (GR) and catalase (CAT) were decreased in all the diabetic groups. CONCLUSIONS: The results indicated that carnosine, aspirin, and a combination eye drops are effective against the onset and development of diabetic cataract in rats. Most important, the effect of combination eye drops is better than aspirin only.

Polaprezinc attenuates the Helicobacter pylori-induced gastric mucosal leucocyte activation in Mongolian gerbils--a study using intravital videomicroscopy

            (Suzuki, Mori et al. 2001) Download

BACKGROUND: We previously demonstrated that Helicobacter pylori colonization evokes gastric mucosal inflammation and an extensive increase in lipid peroxides and glutathione in Mongolian gerbils. Zinc and its derivative, polaprezinc, have been reported to be potent antioxidants in gastric mucosa. AIM: To examine the effect of polaprezinc on gastric mucosal oxidative inflammation in H. pylori-colonized Mongolian gerbils. METHODS: Sixty-eight male Mongolian gerbils were orally inoculated with H. pylori (ATCC43504, 5 x 10(8) CFUs/gerbil; H. pylori group) and 35 gerbils were inoculated with the culture media (control group). Twenty-two gerbils in the H. pylori and 13 gerbils in the control group were fed with diets containing polaprezinc (0.06%, 100 mg/kg, 10 times the usual clinical dose) (H. pylori + polaprezinc group, polaprezinc group). The remaining gerbils were fed a standard laboratory chow diet. Neutrophil infiltration, assessed histologically and by the activity of myeloperoxidase, the contents of CXC-chemokine (GRO/CINC-1-like protein) and the contents of thiobarbituric acid-reactive substances, was evaluated in each group 12 weeks after the inoculation. Separately, gastric mucosal leucocyte activation and capillary perfusion were also assessed using intravital microscopy 2, 4, 8 and 12 weeks after the inoculation. RESULTS: In all H. pylori-inoculated animals, the bacterial infection persisted throughout the experimental period. Gastric mucosal lesion formation in the H. pylori group was significantly inhibited in the H. pylori + polaprezinc group. Elevated levels of myeloperoxidase activity, GRO/CINC-1 and thiobarbituric acid-reactive substances in the H. pylori group at 12 weeks were attenuated significantly by polaprezinc treatment. Enhanced levels of venular leucocyte activation observed in the H. pylori group were attenuated significantly in the H. pylori + polaprezinc group during both the early phase (2 weeks) and late phase (12 weeks). CONCLUSION: Polaprezinc inhibited H. pylori-associated gastric mucosal oxidative inflammation, including initial micro-vascular leucocyte activation, in Mongolian gerbils.


Polaprezinc (Zinc L-carnosine) is a potent inducer of anti-oxidative stress enzyme, heme oxygenase (HO)-1 - a new mechanism of gastric mucosal protection

            (Ueda, Ueyama et al. 2009) Download

Heme oxygenase (HO)-1 is implicated in cytoprotection in various organs. We tested a possibility that polaprezinc (PZ), an anti-ulcer drug, could induce HO-1 in the gastric mucosa. Male 6-week-old Wistar rats were intragastrically administered PZ. Gastric expression of HO-1 was assessed by real time RT-PCR and western blotting, and localization of HO-1 was observed by in situ hybridization and immunohistochemistry. The levels of HO-1 mRNA were increased in a dose-dependent manner. The levels of HO-1 mRNA were increased 4-fold by PZ at the dose of 200 mg/kg at 3 h as compared with control levels. The levels of immunoreactive HO-1 were increased 3-fold at 6 h. Signals for HO-1 mRNA and immunoreactivity were detected strongly in the surface gastric mucosal cells and moderately in the gastric macrophages. Treatment with an HO-1 inhibitor, stannous mesoporphyrin (SnMP) significantly worsened the HCl-induced acute gastric mucosal lesions and increased the apoptosis of mucosal cells. Mucosal lesions were decreased by pretreatment with PZ, while they were increased by co-administration with SnMP. These data indicate for the first time that PZ is an effective inducer of HO-1 in the stomach. PZ-induced HO-1 functions as a part of the mucosal protective effects of PZ.

Effect of carnosine, aminoguanidine, and aspirin drops on the prevention of cataracts in diabetic rats

            (Yan, Guo et al. 2008) Download

PURPOSE: To investigate the effect of carnosine (CA), aminoguanidine (AG), and aspirin (ASA) drops, all inhibitors of glycation, on the development of diabetic cataract in rat. METHODS: Rats were made diabetic with streptozotocin, and based on the level of plasma glucose, they were assigned as non-diabetic rats (<14 mmol/l plasma glucose) and diabetic rats (>14 mmol/l plasma glucose). Animals in the treated groups received CA, AG, and ASA as drops to the left eyes starting from the day of streptozotocin injection. Progression of lens opacification was recorded using the slit lamp at regular time intervals. All the rats were killed after the week 13, and the levels of advanced glycation end products (AGE), glutathione reductase (GR), catalase (CAT), and glutathione (GSH) were determined. RESULTS: Lens opacification progressed in a biphasic manner in the diabetic rats, an initial slow increase during the first eight weeks of diabetes followed by a steep increase in the next five weeks. Carnosine treatment delayed the progression of cataracts in diabetic rats, and the delay was statistically significant on the fourth week of diabetes (p<0.05, when compared with untreated moderately diabetic rats). A decrease in the antioxidant enzymes of CAT and the level of GSH was found in the lens of the untreated diabetic rats at 13 weeks after injection. Some protection was provided in the treated eyes. The level of glycation in the untreated diabetic rats was significantly higher than that in the normal rats (p<0.001). After treatment with CA, AG, and ASA, those diabetic rats had a lower level of glycated lens protein compared to the untreated diabetic rats (p<0.001). CONCLUSIONS: These results thus suggest that the effect of CA, AG, and ASA is indeed inhibition of the formation of AGEs. However, the effect of CA, AG, and ASA is overwhelmed by the excessive accumulation of AGEs in the severely diabetic rats. CA compared with AG and ASA treatment can delay the progression of lens opacification in the diabetic rats only during the earlier stages. It also protects against the inactivation of enzymes.


References

Babizhayev, M. A., L. Burke, et al. (2009). "N-Acetylcarnosine sustained drug delivery eye drops to control the signs of ageless vision: glare sensitivity, cataract amelioration and quality of vision currently available treatment for the challenging 50,000-patient population." Clin Interv Aging 4: 31-50.

Balion, C. M., C. Benson, et al. (2007). "Brain type carnosinase in dementia: a pilot study." BMC Neurol 7: 38.

Corona, C., V. Frazzini, et al. (2011). "Effects of dietary supplementation of carnosine on mitochondrial dysfunction, amyloid pathology, and cognitive deficits in 3xTg-AD mice." PLoS One 6(3): e17971.

Hipkiss, A. R. (2009). "Carnosine, diabetes and Alzheimer's disease." Expert Rev Neurother 9(5): 583-5.

Hipkiss, A. R. (2010). "Aging, Proteotoxicity, Mitochondria, Glycation, NAD and Carnosine: Possible Inter-Relationships and Resolution of the Oxygen Paradox." Front Aging Neurosci 2: 10.

Holliday, R. and G. A. McFarland (1996). "Inhibition of the growth of transformed and neoplastic cells by the dipeptide carnosine." Br J Cancer 73(8): 966-71.

Janssen, B., D. Hohenadel, et al. (2005). "Carnosine as a protective factor in diabetic nephropathy: association with a leucine repeat of the carnosinase gene CNDP1." Diabetes 54(8): 2320-7.

Matsukura, T. and H. Tanaka (2000). "Applicability of zinc complex of L-carnosine for medical use." Biochemistry (Mosc) 65(7): 817-23.

Matsuu-Matsuyama, M., K. Shichijo, et al. (2008). "Protection by polaprezinc against radiation-induced apoptosis in rat jejunal crypt cells." J Radiat Res (Tokyo) 49(4): 341-7.

Min, J., M. C. Senut, et al. (2008). "Differential neuroprotective effects of carnosine, anserine, and N-acetyl carnosine against permanent focal ischemia." J Neurosci Res 86(13): 2984-91.

Ohata, S., C. Moriyama, et al. (2010). "Polaprezinc Protects Mice against Endotoxin Shock." J Clin Biochem Nutr 46(3): 234-43.

Renner, C., N. Zemitzsch, et al. (2010). "Carnosine retards tumor growth in vivo in an NIH3T3-HER2/neu mouse model." Mol Cancer 9: 2.

Shi, Q., H. Yan, et al. (2009). "Effect of a combination of carnosine and aspirin eye drops on streptozotocin -- induced diabetic cataract in rats." Mol Vis 15: 2129-38.

Suzuki, H., M. Mori, et al. (2001). "Polaprezinc attenuates the Helicobacter pylori-induced gastric mucosal leucocyte activation in Mongolian gerbils--a study using intravital videomicroscopy." Aliment Pharmacol Ther 15(5): 715-25.

Tomonaga, S., T. Tachibana, et al. (2004). "Effect of central administration of carnosine and its constituents on behaviors in chicks." Brain Res Bull 63(1): 75-82.

Ueda, K., T. Ueyama, et al. (2009). "Polaprezinc (Zinc L-carnosine) is a potent inducer of anti-oxidative stress enzyme, heme oxygenase (HO)-1 - a new mechanism of gastric mucosal protection." J Pharmacol Sci 110(3): 285-94.

Yan, H., Y. Guo, et al. (2008). "Effect of carnosine, aminoguanidine, and aspirin drops on the prevention of cataracts in diabetic rats." Mol Vis 14: 2282-91.