The objective of the present investigation was to ascertain the impact of in ovo administration of L-carnosine on physiological indicators in neonatal broiler chickens. A total of 280 viable broiler eggs were allocated to 7 distinct groups: control, Sham in ovo injection of sterile water on d 7 of incubation. Groups 3 and 4 were subjected to in ovo injections of L-carnosine (25 and 50 µg) on d 7 of incubation. Group 5, functioning as a sham in ovo, received an injection of sterile water on d 18 of incubation. Groups 6 and 7 were in ovo injected with L-carnosine (25 and 50 µg) on d 18 of incubation. All eggs were subjected to incubation, and the hatching rate and body weight were measured post-hatch. Subsequently, blood samples were collected, and the levels of biochemical constituents in the serum were determined. Based on the outcomes, the administration of L-carnosine (50 µg) on d 7 of incubation led to a significant increase in post-hatch body weight compared to the control group (P < 0.05). The in ovo injection of L-carnosine (25 and 50 µg) on d 7 and 18 of incubation resulted in a significant decrease in the levels of serum glucose, triglyceride (TG), low-density lipoprotein (LDL), phosphorus (P), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine transaminase (ALT) in the newly hatched chickens (P < 0.05). Furthermore, the in-ovo injection of L-carnosine (25 and 50 µg) on d 7 and 18 of incubation led to a significant increase in the levels of serum high-density lipoprotein (HDL), calcium, and total protein (TP) in the newly hatched chickens (P < 0.05). Nonetheless, L-carnosine did not have a significant effect on the levels of serum IgY and IgA in the newly hatched chickens (P > 0.05). These findings indicate that the in ovo administration of L-carnosine yielded favorable outcomes in neonatal broiler chickens.

Dietary l-carnosine supplementation has been shown to enhance animal performance and improve meat quality. However, the mechanisms underlying the effects of l-carnosine on the physiological functions of animals have not been fully elucidated. We investigated the effects of dietary l-carnosine supplementation on growth performance, intestinal microbiota diversity, and the serum metabolome in fattening lambs to reveal the molecular mechanism underlying the effect of l-carnosine on the growth performance of sheep. Sixty 3-month-old male crossbred lambs (Dorper ♂ × Small Tail Han ♀) with an average body weight of 30 ± 5 kg were randomly divided into two groups: a control group (group C) fed a basal diet, and an experimental group (group L) fed a basal diet supplemented with 400 mg/kg of l-carnosine. At the end of the 60-day experiment, all sheep were weighed, and fecal and blood samples were collected from 12 random sheep. The fecal microbiota was analyzed using 16S rRNA sequencing, and serum metabolites were analyzed using liquid chromatography-tandem mass spectrometry. Spearman correlation analysis was employed to assess the associations between intestinal microbiota and serum metabolite biomarkers. The results showed that weight gain and daily weight gain were significantly increased in group L compared to group C ( < 0.01). The dominant phyla in the intestinal microbiota (Firmicutes and Bacteroidetes) did not significantly differ between the two groups ( > 0.05). At the genus level, the abundances of ( < 0.01) and ( < 0.001) were higher, whereas those of and were significantly lower in group L than in group C ( < 0.05). Non-targeted metabolomics identified 68 differentially abundant biomarkers (VIP > 1,  < 0.05). The content of pyridine N-oxide glucuronide was significantly downregulated ( < 0.01), whereas those of l-histidinol, d-apiose, and isodomedin were significantly upregulated in group L versus group C ( < 0.001). and were positively correlated with l-histidine, d-apiose, and l-erythrulose ( < 0.001), whereas was negatively correlated with pyridine N-oxide glucuronide ( < 0.001). This study provided new insights into the effects of l-carnosine on the intestinal microbiota and nutrient metabolism in fattening sheep that will be helpful for the future application of l-carnosine in ruminants.

Carnosine (β-alanyl-l-histidine), a dipeptide, is an endogenous antioxidant widely distributed in excitable tissues like muscles and the brain. Although discovered more than a hundred years ago and having been extensively studied in the periphery, the role of carnosine in the brain remains mysterious. Carnosinemia, a rare metabolic disorder with increased levels of carnosine in urine and low levels or absence of carnosinase in the blood, is associated with severe neurological symptoms in humans. This review deals with the role of carnosine in the brain in both physiological and pathological conditions, with a focus on preclinical evidence suggesting a high therapeutic potential of carnosine in neurodegenerative disorders. We review carnosine and carnosinemia's discoveries and the extensive research on the role and benefits of carnosine in the periphery. We then turn to carnosine's biochemistry and distribution in the brain. Using an array of recent observations as a foundation, we draw a parallel with the role of carnosine in muscles and speculate on the role of carnosine in promoting the metabolic support of neurons by glial cells. Finally, carnosine has been shown to exert a multimodal activity including inhibition of protein cross-linking and aggregation of amyloid-β and related proteins, free radical generation, nitric oxide detoxification, and an anti-inflammatory activity. It could thus play an important role in the prevention and treatment of neurodegenerative diseases such as Alzheimer's disease. We discuss the potential of carnosine in this context and speculate on new preclinical research directions.

Chicken breast extract (CBEX) is obtained via hot water extraction of chicken breast and contains among its primary constituents carnosine and anserine, which are histidine-containing dipeptides present in the muscle tissues of most vertebrate species. Dietary intake of CBEX has been previously shown to buffer hydrogen ions formed during high-intensity exercise in human skeletal muscle cells, thereby inhibiting a decrease in muscle cell pH and subsequent muscle fatigue. The objective of this paper is to report the results of safety studies completed on CBEX. CBEX was determined to have an oral LD(50) value of more than 6000 mg/kg body weight in rats. Gavage doses of 500 or 2000 mg CBEX/kg body weight/day administered to rats for 90 days produced no toxicologically significant, dose-related, differences between control and treated animals with respect to body weight gain, food consumption, behavioral effects, hematological and clinical chemistry parameters, absolute and relative organ weights, or gross and microscopic findings. In the presence or absence of metabolic activation, CBEX exerted no mutagenic activity in the Ames assay conducted in various strains of Salmonella typhimurium and Escherichia coli. The results of these studies support the safety of CBEX as a potential dietary source of carnosine and anserine.

BACKGROUND AND PURPOSE:An urgent need exists to develop therapies for stroke that have high efficacy, long therapeutic time windows, and acceptable toxicity. We undertook preclinical investigations of a novel therapeutic approach involving supplementation with carnosine, an endogenous pleiotropic dipeptide. METHODS:Efficacy and safety of carnosine treatment was evaluated in rat models of permanent or transient middle cerebral artery occlusion. Mechanistic studies used primary neuronal/astrocytic cultures and ex vivo brain homogenates. RESULTS:Intravenous treatment with carnosine exhibited robust cerebroprotection in a dose-dependent manner, with long clinically relevant therapeutic time windows of 6 hours and 9 hours in transient and permanent models, respectively. Histological outcomes and functional improvements including motor and sensory deficits were sustained on 14th day poststroke onset. In safety and tolerability assessments, carnosine did not exhibit any evidence of adverse effects or toxicity. Moreover, histological evaluation of organs, complete blood count, coagulation tests, and the serum chemistry did not reveal any abnormalities. In primary neuronal cell cultures and ex vivo brain homogenates, carnosine exhibited robust antiexcitotoxic, antioxidant, and mitochondria protecting activity. CONCLUSIONS:In both permanent and transient ischemic models, carnosine treatment exhibited significant cerebroprotection against histological and functional damage, with wide therapeutic and clinically relevant time windows. Carnosine was well tolerated and exhibited no toxicity. Mechanistic data show that it influences multiple deleterious processes. Taken together, our data suggest that this endogenous pleiotropic dipeptide is a strong candidate for further development as a stroke treatment.

Since l-carnosine has shown effectiveness in improvement of cognition in patients with schizophrenia, this 8-week, randomized, double-blind, placebo-controlled pilot study was conducted. Sixty-three patients with chronic schizophrenia, who were clinically stable on a stable dose of risperidone, entered the study. The patients were randomly assigned to l-carnosine (2 gr/day in two divided doses) or placebo for eight weeks. The patients were assessed using the positive and negative syndrome scale (PANSS), extrapyramidal symptom rating scale (ESRS), and Hamilton depression rating scale (HDRS) during the study course. Sixty patients completed the trial. L-carnosine resulted in greater improvement of negative scores as well as total PANSS scores but not positive subscale scores compared to placebo. HDRS scores and its changes did not differ between the two groups. Both groups demonstrated a constant ESRS score during the trial course. Frequency of other side effects was not significantly different between the two groups. In a multiple regression analysis model (controlled for positive, general psychopathology, depressive and extrapyramidal symptoms, as well as other variables), the treatment group significantly predicted changes in primary negative symptoms. In conclusion, l-carnosine add-on therapy can safely and effectively reduce the primary negative symptoms of patients with schizophrenia.

This pilot trial reports the effects of L-carnosine administration on autonomic nervous system performance, brain metabolism, and various patient- and clinician-reported outcomes in a case series of patients with multiple sclerosis (MS). We hypothesized that medium-term L-carnosine supplementation would improve selected patient- and clinician-reported outcomes in MS patients, with no negative effects on self-reported side effects. L-carnosine (2 g/day) was administered orally for 8 weeks in 2 women and one man suffering from MS. The intensity of symptoms and signs of MS after L-carnosine administration diminished in 5 out of 7 domains in CASE 1, in 3 out of 7 domains in CASE 2, and one domain in CASE 3; general fatigue was reduced in all 3 cases at the follow-up. This was accompanied by an improved walking distance to exhaustion in all patients, with values improved for 51.1% in CASE 1, 19.5% in CASE 2, and 2.1% in CASE 3 at 8-week follow-up. Tests of autonomic cardiovascular reflexes demonstrate normalized parasympathetic modulation and balanced sympathetic function after L-carnosine intervention in all MS cases. An increase in serum total antioxidant capacity (TAC) was found at 8-week follow-up in all patients (from 4.6 to 49.6%); this was accompanied by lower blood lactate at post-administration in all cases (23.5% on average). Single-voxel 1.5 T MR spectroscopy revealed increased brain choline-contained compounds (18.9% on average), total creatine (21.2%), and myo-inositol levels (12.3%) in girus cinguli at 8-week follow-up in all MS cases. This case study demonstrates that an 8-week intervention with L-carnosine appears to be a safe and beneficial therapeutic strategy with regard to the reduction of presence and severity of symptoms of MS.

Sleep disorders are frequently reported in autistic patients. Evidences suggest that increased oxidative stress and reduced antioxidants may play a major role in the pathogenesis of these disorders. Carnosine acts as an antioxidant, antitoxic and neuroprotective agent. The aim of this trial study was to examine the effects of carnosine supplementation on the sleep disorders and severity of autism core symptoms in autistic patients. In this double-blind, randomized clinical trial, 43 autistic patients (31 boys and 12 girls; aged 4 to 16 years) were divided into two groups of carnosine and control that received 500 mg of carnosine and 500 mg of placebo per day for 2 months, respectively. Sleep disorders were measured using Children's Sleep Habits Questionnaires. Gilliam Autism Rating Scale 2 was used to assess the effects of carnosine supplementation on the autism severity. Carnosine supplementation did not change anthropometric indices (p > 0.05) and showed no effect on autism severity (p > 0.05), whereas it significantly reduced sleep duration (p = 0.04), parasomnias (p = 0.02) and total sleep disorders score by 7.59% (p = 0.006) when compared with the control group. The results suggest that carnosine supplementation could be effective in improving sleep disturbances, in particular sleep duration and parasomnias subscales.

OBJECTIVES:This study aimed to investigate the efficacy and tolerability of l-carnosine as an add-on to methylphenidate in management of children with attention-deficit/hyperactivity disorder (ADHD). METHODS:This was an 8-week, randomized, double-blind placebo-controlled study. Fifty-six drug-free children and adolescents aged 6-17 years old with a diagnosis of ADHD entered the study. The patients were randomly assigned to l-carnosine (800 mg/d in two divided doses) or placebo plus methylphenidate (0.5-1.5 mg/kg/d) for 8 weeks. Children were assessed using the Teacher and Parent ADHD Rating Scale-IV (ADHD-RS-IV) at baseline and at weeks 4 and 8 postbaseline. RESULTS:Fifty patients completed the study, and all had two postbaseline measurements. Using the general linear model repeated measures, significant effect was observed for time × treatment interaction on total and inattention subscales of the Parent ADHD-RS (Greenhouse-Geisser corrected: F = 3.783, df = 1.444, p = 0.041 and F = 4.032, df = 1.600, p = 0.030). Improvements in the Teacher ADHD-RS were not significantly different between the two groups in total (Greenhouse-Geisser corrected: F = 0.200, df = 1.218, p = 0.705), as well as inattention and hyperactivity subscale scores (p = 0.956 and 0.281, respectively). The frequency of side effects was not significantly different between the two treatment arms. CONCLUSIONS:l-carnosine, as a supplementary medication, might be beneficial in treatment of children with ADHD. However, further investigations and different doses of l-carnosine are required to replicate these findings in children with ADHD.

Background Horizontal neck wrinkle formation is gaining more attention among cosmetic practitioners and clients. To date, hyaluronic acid products are one of the most common treatment options for this aesthetic concern. However, different therapeutic strategies should be given to solve the problem due to multiple etiological reasons. Given that oxidative damage plays a critical role in neck wrinkle formation, anti-oxidative compounds are now considered by physicians when making a treatment plan. Aims To evaluate the efficacy and safety of a non-cross-linked hyaluronic acid filler in combination with L-carnosine in treating horizontal neck wrinkles. Methods Thirteen patients with a Wrinkle Assessment Scale (WAS) of 2-5 for horizontal neck wrinkles were treated with L-carnosine-containing non-cross-linked hyaluronic acid. Participants were followed-up for 3 months after treatment. The post-treated WAS scores evaluated by physicians were collected when patient satisfaction was surveyed. Any post-treatment adverse events were recorded. Results With a single injection of the above filler, the physician-evaluated WAS scores improved by at least one score at one month and the improvement kept consistent as far as three months after injection. According to the last follow-up visit, 11/13 patients were satisfied with the treatment effect of their neck wrinkle. Moreover, adverse events were rare after filler injection, except for local complications that were considered common reactions to the filler injection procedure. Conclusion The non-cross-linked hyaluronic acid filler containing L-carnosine is safe and effective for treating horizontal neck wrinkles.Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

AIMS:The prevalence of metabolic syndrome (MetS) is increasing in several countries. The MetS is characterized by the occurrence of at least three of the following risk factors: decreased high-density lipoprotein cholesterol, increased blood pressure, raised fasting blood glucose, elevated triglycerides, and abdominal obesity. There is a growing evidence of the role of l-carnosine in improving lipid profile and enhancement of the antioxidant activity. However, the effects of l-carnosine on development of MetS are unknown. MAIN METHODS:Male Wistar rats were randomly assigned to receive either; conventional diet (control), high-fat high-carbohydrate diet (HFHCD), l-carnosine and conventional diet (L-Car), or l-carnosine and high-fat high-carbohydrate diet (HFHCD and L-Car) for 16 weeks. Central obesity, systolic blood pressure, lipid profile, glucose hemostasis, levels of leptin and adiponectin were evaluated on week 16. KEY FINDINGS:Rats that received HFHCD for 16 weeks showed MetS phenotype such as central obesity, increased blood pressure and glucose, as well as an altered lipid profile (P < 0.05). l-Carnosine supplementation to MetS rats significantly reduced abdominal obesity, blood pressure and glucose, and normalized total cholesterol and low density lipoprotein cholesterol levels (P < 0.05). Insulin, leptin and adiponectin concentrations were not affected by l-Carnosine (P > 0.05). SIGNIFICANCE:l-carnosine has beneficial effects on ameliorating the manifestations of MetS in rats.

BACKGROUND:Evidence for antidepressant effects of L-Carnosine was shown in some experimental studies. In this study we tried to evaluate the efficacy and tolerability of L-Carnosine combination therapy in treatment of patients with major depressive disorder (MDD). METHODS:Fifty-eight patients with MDD (DSM-V) and Hamilton Depression Rating Scale (HAM-D) score ≥ 19 were randomized to receive either 400 mg twice daily L-Carnosine or placebo in addition to citalopram (maximum dosage of 40 mg/day) for six weeks in a randomized double-blind, and placebo-controlled study. Patients were assessed using the HAM-D scale at baseline and weeks 2, 4, and 6. RESULTS:Fifty-two patients completed the trial. General linear model repeated measure showed significant difference for time × treatment on HAM-D score [F = 3.17, df = 2.39, p-value = 0.03]. Significantly greater improvement was detected in HAM-D score of the L-Carnosine group compared with the placebo group from baseline to weeks 2, 4 and 6 [Ps = 0.013, 0.028 and 0.023; respectively]. Patients in the L-Carnosine group experienced significantly greater response and remission rate than the placebo group [Ps = 0.023 and 0.012; respectively]. There was no significant difference between the two groups in baseline parameters and frequency of side effects. LIMITATIONS:Short follow-up period and small population size were two important limitations of this study. CONCLUSIONS:L-Carnosine combination therapy with citalopram can effectively improve symptoms of patients with major depressive disorder. Rapid-onset antidepressant effects of L-Carnosine were also shown which need further investigation.

The effects of dietary supplementation of L-carnosine (beta-alanyl-L-histidine) on ischemia/reperfusion-induced acute renal failure (ARF) in rats were examined. Ischemic ARF was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal functional parameters such as blood urea nitrogen, plasma creatinine, creatinine clearance, urine flow, urinary osmolality and fractional excretion of sodium were measured. Renal function in ARF rats markedly decreased at 1 d after reperfusion. Prior feeding of L-carnosine-containing diet (0.0001 w/w%) for 2 weeks attenuated the ischemia/reperfusion-induced renal dysfunction. Histopathological examination of the kidney of ARF rats revealed severe renal damages, such as tubular necrosis, proteinaceous casts in tubuli and medullary congestion, which were also significantly suppressed by the dietary supplementation of L-carnosine. These findings strongly suggest that L-carnosine supplementation is useful as a prophylactic treatment in the development of the ischemic ARF.

SCOPE:The intestinal epithelium is nourished by various nutrients and subjected to persistent and widespread feed-derived mycotoxin stress. l-Carnosine (LC) possesses robust antioxidant activity; however, its role in protecting intestinal mucosa against deoxynivalenol (DON) is still unclear. METHODS AND RESULTS:In this study, 300 mg kg BW LC and 3 mg kg BW DON are orally administered to mice either alone or in combination for 10 days to investigate the role of LC in protecting the intestine against DON. This study found that LC alleviates the growth retardation of mice and repairs the damaged jejunal structure and barrier functions under DON exposure. LC rescues the intestinal stem cells (ISCs), increases the growth advantage in enteroids derived from jejunal crypts of mice in each group ex vivo, improves the proliferation and apoptosis of intestinal cells, and promotes ISC differentiation into absorptive cells, goblet cells, and Paneth cells. Furthermore, LC activates Nrf2 signaling by binding to Keap1 to reverse the striking DON-induced increase in ROS levels. CONCLUSION:The study findings unveil that LC potentiates the antioxidant capacity of ISCs by regulating the Keap1/Nrf2 signaling pathway, which contributes to the intestinal epithelial regeneration response to DON insult.

The outcomes of supplementation with L-carnosine have been investigated in clinical trials in children with autism spectrum disorder (ASD). However, reports on the effects of L-carnosine in humans have been inconsistent, and the efficacy of L-carnosine supplementation for improving ASD symptoms has yet to be investigated in animal studies. Here, we examined the effects of oral supplementation with L-carnosine on social deficits in CD157KO mice, a murine model of ASD. Social deficits in CD157KO mice were assessed using a three-chamber social approach test. Oral supplementation with L-carnosine attenuated social behavioral deficits. The number of c-Fos-positive oxytocin neurons in the supraoptic nucleus and paraventricular nucleus was increased with L-carnosine supplementation in CD157KO mice after the three-chamber social approach test. We observed an increase in the number of c-Fos-positive neurons in the basolateral amygdala, a brain region involved in social behavior. Although the expression of oxytocin and oxytocin receptors in the hypothalamus was not altered by L-carnosine supplementation, the concentration of oxytocin in cerebrospinal fluid was increased in CD157KO mice by L-carnosine supplementation. These results suggest that L-carnosine supplementation restores social recognition impairments by augmenting the level of released oxytocin. Thus, we could imply the possibility of a safe nutritional intervention for at least some types of ASD in the human population.

Corticosterone, an end product of the hypothalamic-pituitary-adrenal (HPA) axis, is a crucial stress hormone. A dysregulated HPA axis and corticosterone release play pivotal roles in the onset and persistence of symptoms of stress-related psychiatric disorders, such as anxiety. The intake of nutrients, probiotics, and prebiotic supplements decreases blood corticosterone levels. The dipeptide L-carnosine is composed of beta-alanine and L-histidine and is commercially available as a nutritional supplement for recovery from fatigue. L-carnosine is involved in stress-induced corticosterone responses and anxiety behaviors in rodents. Here, we assessed the effect of L-carnosine in CD157 knockout (KO) mice, a murine model of autism spectrum disorder (ASD). The uptake of L-carnosine suppressed the increase in plasma corticosterone levels in response to acute stress and attenuated anxiety-like behaviors in CD157 KO mice. These results suggest that L-carnosine supplementation may relieve anxiety by suppressing excessive stress responses in individuals with ASD.

This study aimed to investigate the effect of maternal supplementation of L-carnosine on improved reflexive motor behaviors in mice offspring. Forty pregnant female NMRI mice were allocated into four groups. In the control group, mice received water, while in groups 2-4, female mice received supplementation of the L-carnosine (0.001, 0.01, or 0.1 mg/kg) at gestation days (G.D.) 5, 8, 11, 14, and 17. Newborn male pups were selected, and reflexive motor behaviors were analyzed on days 5, 7, 10, and 10-15, respectively. Serum malondialdehyde(MDA), superoxide dismutase(SOD), glutathione peroxidase(GPx) and total antioxidant status(TAS) of was determined in offspring's. According to findings, prenatal supplementation of the L-carnosine significantly increased ambulation score, surface righting, hind-limb suspension score, grip strength, front-limb suspension time, and negative geotaxis in mice offspring (P < 0.05). Hind-limb foot angle decreased in mice offspring by maternal supplementation of the L-carnosine (P < 0.05). Prenatal supplementation of the L-carnosine significantly decreased the MDA and increased the SOD, GPx, and TAS levels in offspring (P < 0.05). These results suggested maternal supplementation of the L-carnosine improved reflexive motor behaviors and antioxidant status in mice offspring.

OBJECTIVE:To elucidate the implications of L-carnosine on interleukin-1α (IL-1α)-induced inflammation of lacrimal glands (LGs). MATERIALS AND METHODS:Forty rabbits were divided equally into four groups: control group (G1), IL-1α (G2), L-carnosine (G3), and L-carnosine plus IL-1α (G4). Several clinical, histopathological, immunohistochemical, morphometric, and biochemical investigations were performed, followed by statistical analysis to diagnose the presence of dry eye disease (DED). RESULTS:The LGs of G2 rabbits showed degeneration of the acinar cells, increased deposition of collagen fibers, and marked immunoexpression of FasL; elevated levels of interferon-γ, tumor necrosis factor-α, transforming growth factor-β1, and malondialdehyde; and decreased levels of glutathione peroxidase, superoxide dismutase, catalase, and reactive oxygen species compared with those of G1 rabbits. In contrast, administration of L-carnosine to G4 rabbits revealed marked improvement of all previously harmful changes in G2 rabbits, indicating the cytoprotective effects of L-carnosine against IL-1α-induced inflammation of LGs. CONCLUSIONS:IL-1α induced inflammation of LGs and eye dryness via oxidative stress, proinflammatory, apoptotic, and profibrotic effects, whereas L-carnosine mitigated DED through antioxidant, anti-inflammatory, antiapoptotic, and antifibrotic effects on LGs. Therefore, this work demonstrates for the first time that L-carnosine may be used as adjuvant therapy for the preservation of visual integrity in patients with DED.HighlightsIL-1α induced dry eye disease through its oxidative stress, proinflammatory, apoptotic and profibrotic effects on the lacrimal glands of rabbit.L-carnosine has antioxidant, anti-inflammatory, antiapoptotic and antifibrotic effects.L-carnosine mitigated IL-1α induced dry eye disease via elevating the levels of FasL, IFN-γ, TNF-α, TGFβ1 and MDA as well as reducing the levels of antioxidants (GPx, SOD, and catalase) and ROS in the lacrimal glands of rabbit.L-carnosine could be used as a novel adjuvant therapy for the treatment of dry eye disease.

BACKGROUND:Chronic kidney disease (CKD) is a major health problem worldwide. Oxidative stress is one of the mediators of this disease. Systemic complications of oxidative stress are involved in the pathogenesis of hypertension, endothelial dysfunction, shortened erythrocyte lifespan, deformability, and nitric oxide (NO) dysfunction. L-carnosine is known as an antioxidant. In this study, our aim was to investigate the effect of carnosine on hemorheologic and cardiovascular parameters in CKD-induced rats. MATERIAL AND METHODS:We used 4-month-old male Sprague-Dawley rats divided into 4 groups of 6 rats each. Three days after subtotal nephrectomy and sham operations, the surviving rats were divided into the 4 groups; 1) Sham (S), 2) Sham+Carnosine (S-C), 3) Subtotal nephrectomy (Nx), and 4) Subtotal nephrectomy + Carnosine (N-C). Carnosine was injected intraperitoneally (i.p.) (50 mg/kg) for 15 days. The control group received the same volume of physiological saline. RESULTS:In CKD rats, malondialdehyde (MDA) levels were increased, and NO and RBC deformability were decreased compared to Sham. Carnosine treatment decreased MDA levels, improved RBC (red blood cell) ability to deform, and increased NO levels. However, carnosine did not affect blood pressure levels in these rats. CONCLUSIONS:We found that carnosine has beneficial effects on CKD in terms of lipid peroxidation and RBC deformability. Carnosine may have a healing effect in microcirculation level, but may not have any effect on systemic blood pressure in CKD-induced rats.

BACKGROUND:Dysregulation of glutamate is implicated in the pathogenesis of obsessive-compulsive disorder (OCD). Consistently, glutamate-modulating agents, such as riluzole and memantine have been used in OCD treatment. Previous research has identified some neuroprotective role for L-carnosine potentially via its modulatory effect on glutamate. Here, we assessed the efficacy of L-carnosine as adjuvant to fluvoxamine in OCD treatment. METHODS:Forty-four patients diagnosed with moderate to severe OCD were recruited in a randomized double-blind trial. Patients received either L-carnosine or placebo as adjuvant to fluvoxamine for 10 weeks. The Yale- Brown Obsessive Compulsive Scale (Y-BOCS) was used for assessing the severity of symptoms at baseline and at weeks 4, 8, and 10. RESULTS:General linear model repeated measure showed significant effects for Time × Treatment interaction on total Y-BOCS [F (2.10, 88.42) = 8.66, p < 0.001], obsession [F (1.88, 79.34) = 4.96, p = 0.01] and compulsion [F (1.88, 79.11) = 4.57, p = 0.01]. At week 10, the change from baseline in Y-BOCS scores was 8.86 ± 2.89 (mean ± SD) in the L-carnosine group compared to 5.86 ± 2.88 in the placebo group. CONCLUSION:L-carnosine results in significant reduction of obsessive-compulsive symptoms when used as an adjuvant to fluvoxamine.

Carnosine is a dipeptide formed from the amino acids β-alanine and histidine and found in large amounts in the brain and muscle, especially fast twitch muscle. Carnosine has an antioxidant role and accounts for about 10% of the muscle's ability to buffer the H+ ions produced by high intensity exercise. Due to the interesting role of carnosine, the aim of the study was observe the effects of carnosine intake on pro-antioxidant status in highly trained athletes exposed to intense exercise.Fourteen male athletes from the Polish national kayak and canoe teams participated in placebo-controlled and cross-over study. The athletes were supplemented with 4 g/d carnosine for 14 days. Blood samples were collected before and 30 min, 24 h and 48 h after 2000 m exercise trial. In blood, hydrogen peroxide (H2O2), nitric oxide (NO), markers of RO/NS activity 8-isoprostanes and 3-nitrotyrosine, total (GSHt) and oxidised glutathione (GSSG), antioxidant status (APO) and superoxide dismutase (SOD) were determined. There were not observed statistically significant differences in exercise-induced changes in H2O2 and NO concentrations and SOD activity after carnosine intake. However, carnosine prevented an increase in 8-isoprostanes, 3-nitrotyrosine and GSSG concentrations as well as elevated redox status (GSHt-2GSSG)/GSSG at post-exercise period.Although, oral supplementation with 4 g carnosine did not affect RO/NS generation, it significantly attenuated exercise-induced glutathione loss, reduced oxidation/nitration markers concentration and SOD activity. These results suggest that carnosine could provide antioxidative protection for highly trained athletes.

The antioxidant L-Carnosine is reported to improve negative and cognitive symptoms in Schizophrenia. A randomized double-blind placebo-controlled study was planned to study the effectiveness of adjuvant L-Carnosine therapy in patients with Schizophrenia. 100 eligible patients with predominant negative symptoms as measured by scale for assessment of negative symptoms (SANS total score ≥ 60) and Schizophrenia diagnosis (International Classification of Disorder-Tenth Edition, ICD-10) were recruited. They were randomly allocated to receive a fixed dose of either 400 mg L-Carnosine or identical placebo for 3 months and increased to 800 mg from 13th week till completion of study. Primary outcome measures assessed changes in SANS scores with L-Carnosine at 24 weeks compared to baseline, 4 and 12 weeks. Secondary outcome measures were done to assess the improvement in cognitive symptoms (executive function, attention, and memory) at 24 weeks using subtests of NIMHANS (National Institute for Mental Health and Neurosciences) cognitive battery. Side effects were assessed using adverse events reporting form. The attention scores (p = .023) showed significant differences in patients receiving 800 mg of L-Carnosine at the end of the study. There were no significant differences in negative symptoms in the two arms at study completion. L-Carnosine dosing of 800 mg may be a promising agent to enhance executive functions in Schizophrenia.