Carnosine and vitamin E – a promising pair in the combat against testicular oxidative stress in aged rats

Oxidative stress is considered to play a key role in ageing. Carnosine alone or together with vitamin E may prove to be helpful in dealing with problems of ageing through its antioxidant activity. Testis, by producing steroids and possessing a poor antioxidant system may become a strong target for the chronic oxidative stress generated during ageing. Therefore we investigated the in vivo effect of carnosine alone or together with vitamin E on testicular oxidative stress in aged rats. In this study, young (5 months) and aged (22 months) Wistar rats were used. Carnosine (250 mg kg^?1; i.p.; 5 days per week) and vitamin E (200 mg kg^?1; i.m.; twice per week) were given to aged rats for 2 months. Increased testicular lipid peroxidation and superoxide dismutase activity in aged rats were declined to the levels of young ones by both treatments. Decreased glutathione peroxidase and glutathione transferase activities returned to the level of young's only by carnosine plus vitamin E treatment. Histopathological evaluation described by Johnsen's score, also showed significant improvement with preserved spermatogenesis. Carnosine plus vitamin E treatment appears to stage a powerful performance by attenuating testicular oxidative stress and sparing the antioxidant system.     

Neuroprotective effect of carnosine in the olfactory bulb after vanadium inhalation in a mouse model

Carnosine (β‐alanyl‐L‐histidine) is synthesized in the olfactory system, has antioxidant activity as a scavenger of free radicals and has been reported to have neuroprotective action in diseases which have been attributed to oxidative damage. In neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases, impairment of olfactory function has been described. Vanadium derivatives are environmental pollutants, and its toxicity has been associated with oxidative stress. Vanadium toxicity on the olfactory bulb was reported previously. This study investigates the neuroprotective effect of carnosine on the olfactory bulb in a mice model of vanadium inhalation. Male mice were divided into four groups: vanadium pentoxide (V₂O₅) [0.02 mol/L] inhalation for one hour twice a week; V₂O₅ inhalation plus 1 mg/kg of carnosine administered daily; carnosine only, and the control group that inhaled saline. The olfactory function was evaluated using the odorant test. Animals were sacrificed four weeks after exposure. The olfactory bulbs were dissected and processed using the rapid Golgi method; cytological and ultrastructural analysis was performed and malondialdehyde (MDA) concentrations were measured. The results showed evidence of olfactory dysfunction caused by vanadium exposure and also an increase in MDA levels, loss of dendritic spines and necrotic neuronal death in the granule cells. But, in contrast, vanadium‐exposed mice treated with carnosine showed an increase in dendritic spines and a decrease in neuronal death and in MDA levels when compared with the group exposed to vanadium without carnosine. These results suggest that dendritic spine loss and ultrastructural alterations in the granule cells induced by vanadium are mediated by oxidative stress and that carnosine may modulate the neurotoxic vanadium action, improving the olfactory function.     

Investigation of a new horizon antifungal activity with enhancing the antimicrobial efficacy of ciprofloxacin and its binary mixture via their encapsulation in nanoassemblies: in vitro and in vivo evaluation

The main goal of this study was to prepare and evaluate nanosponges containing ciprofloxacin (CIP) or its binary mixture with N-acetyl carnosine (NAC). Nanosponges were prepared by ultrasound-assisted synthesis technique using hydroxypropyl βeta-cyclodextrin (HPβ-CD), as the polymer and diphenyl carbonate (DPC) as the crosslinker. Entrapment efficiency (EE%) of CIP or its binary mixture with NAC in nanosponges was deduced spectrophotometrically. Nanosponges were characterized using several methods. EE% of CIP or its binary mixture with NAC inside nanosponges ranged from 98.63 ± 3.1 to 100 ± 0.07%. Particle size of nanosponges ranged from 66.7 to 90.1 nm. Release of drugs from nanosponges was biphasic and the release pattern followed Korsmeyer–Peppas model. Ex vivo and in vivo studies results showed that the antibacterial effect was enhanced with encapsulation of drugs in the nanosponge system. Furthermore, a potent antifungal activity was obtained from all examined formulae against Candida albicans (10231). The study revealed that successful encapsulation of CIP or its binary mixture with NAC in nanosponge formulations has innovated a new promising therapeutic activity for both drugs.     

Ergogenic Effects of β-Alanine and Carnosine: Proposed Future Research to Quantify Their Efficacy

β-alanine is an amino acid that, when combined with histidine, forms the dipeptide carnosine within skeletal muscle. Carnosine and β-alanine each have multiple purposes within the human body; this review focuses on their roles as ergogenic aids to exercise performance and suggests how to best quantify the former's merits as a buffer. Carnosine normally makes a small contribution to a cell's total buffer capacity; yet β-alanine supplementation raises intracellular carnosine concentrations that in turn improve a muscle's ability to buffer protons. Numerous studies assessed the impact of oral β-alanine intake on muscle carnosine levels and exercise performance. β-alanine may best act as an ergogenic aid when metabolic acidosis is the primary factor for compromised exercise performance. Blood lactate kinetics, whereby the concentration of the metabolite is measured as it enters and leaves the vasculature over time, affords the best opportunity to assess the merits of β-alanine supplementation's ergogenic effect. Optimal β-alanine dosages have not been determined for persons of different ages, genders and nutritional/health conditions. Doses as high as 6.4 g day(-1), for ten weeks have been administered to healthy subjects. Paraesthesia is to date the only side effect from oral β-alanine ingestion. The severity and duration of paraesthesia episodes are dose-dependent. It may be unwise for persons with a history of paraesthesia to ingest β-alanine. As for any supplement, caution should be exercised with β-alanine supplementation.     

Influence of Imidazole-Dipeptides on Cognitive Status and Preservation in Elders: A Narrative Review

The worldwide increase in the number of patients with dementia is becoming a growing problem, while Alzheimer’s disease (AD), a primary neurodegenerative disorder, accounts for more than 70% of all dementia cases. Research on the prevention or reduction of AD occurrence through food ingredients has been widely conducted. In particular, histidine-containing dipeptides, also known as imidazole dipeptides derived from meat, have received much attention. Imidazole dipeptides are abundant in meats such as poultry, fish, and pork. As evidenced by data from recent human intervention trials conducted worldwide, daily supplementation of carnosine and anserine, which are both imidazole dipeptides, can improve memory loss in the elderly and reduce the risk of developing AD. This article also summarizes the latest researches on the biochemical properties of imidazole dipeptides and their effects on animal models associated with age-related cognitive decline. In this review, we focus on the results of human intervention studies using supplements of poultry-derived imidazole dipeptides, including anserine and carnosine, affecting the preservation of cognitive function in the elderly, and discuss how imidazole dipeptides act in the brain to prevent age-related cognitive decline and the onset of dementia.     

Improved spectral resolution and high reliability of in vivo 1H MRS at 7 T allow the characterization of the effect of acute exercise on carnosine in skeletal muscle

The aims of this study were to observe the behavior of carnosine peaks in human soleus (SOL) and gastrocnemius (GM) muscles following acute exercise, to determine the relaxation times and to assess the repeatability of carnosine quantification by ¹H MRS at 7 T. Relaxation constants in GM and SOL were measured by a stimulated echo acquisition mode (STEAM) localization sequence. For T₁ measurement, an inversion recovery sequence was used. The repeatability of the measurement and the absolute quantification of carnosine were determined in both muscles in five healthy volunteers. For absolute quantification, an internal water reference signal was used. The effect of acute exercise on carnosine levels and resonance lines was tested in eight recreational runners/cyclists. The defined carnosine measurement protocol was applied three times – before and twice after (approximately 20 and 40 min) a 1‐h submaximal street run and additional toe‐hopping. The measured T₁ relaxation times for the C2‐H carnosine peak at 7 T were 2002 ± 94 and 1997 ± 259 ms for GM and SOL, respectively, and the T₂ times were 95.8 ± 9.4 and 81.0 ± 21.8 ms for GM and SOL, respectively. The coefficient of variation of the carnosine quantification measurement was 9.1% for GM and 6.3% for SOL, showing high repeatability, and the intraclass correlation coefficients (ICCs) of 0.93 for GM and 0.98 for SOL indicate the high reliability of the measurement. Acute exercise did not change the concentration of carnosine in the muscle, but affected the shape of the resonance lines, in terms of the shifting and splitting into doublets. Carnosine measurement by ¹H MRS at 7 T in skeletal muscle exhibits high repeatability and reliability. The observed effects of acute exercise were more prominent in GM, probably as a result of the larger portion of glycolytic fibers in this muscle and the more pronounced exercise‐induced change in pH. Our results support the application of the MRS‐based assessment of carnosine for pH measurement in muscle compartments. © 2015 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.     

Physiology and pharmacology of olfactory bulb neurons in dissociated cell culture

Cells from olfactory bulbs of embryonic rats were grown in dissociated cell culture for up to 5 weeks. Both neurons and non-neuronal cells grew in these cultures, with a variety of neuronal populations appearing. A population of 20–25% of the neurons were GABAergic by the criterion of [³H]GABA uptake. Electrophysiologic measurements were made of the baseline activity of the cultured neurons. Cells showed a mean resting potential of60.1 ± 1.2mV and a mean input resistance of87.6 ± 9.5MΩ. All cells were sensitive to microperfusion of GABA with half-maximal effect occurring at about 20 μM. Glutamate was universally excitatory but with variations in degree. Carnosine (β-Ala-l-His), tested over the concentration range of 10 nM to 100 μM, had no effect on input resistance, resting potential, action potential shape, on-going synaptic activity or the responsiveness to either GABA or glutamate. These results are further evidence against a role for carnosine as the excitatory transmitter of the primary olfactory afferents.     

Carnosine inhibits cataract formation and inactivation of Na+-K+ATPase induced by a glucocorticoid

To investigate whether carnosine can inhibit cataract formation and protect Na⁺-K⁺ATPase against inactivation induced by a glucocorticoid. METHODS: Two hundred and twenty clear lenses cultured in vitro were randomly divided into five groups: control group (DMEM), steroid group (DMEM+Dexamethason 10μmol/L), lower concentration carnosine-treated group (DMEM+Dexamethason 10μmol/L+Carnosine 2mmol/L), higher concentration carnosine-treated group (DMEM+Dexamethason 10μmol /L+ Carnosine 5mmol/L) and carnosine group (DMEM + Carnosine 5mmol/L). Progression of cataract formation was evaluated daily using a dissecting microscope. On 1, 3, 5 and 7 days, 10 lenses of every group were homogenized and the activity of Na^{+-K+ATPase was measured by using spectrophotometer. RESULTS: During the incubation, mistlike opacity was observed in the lenses of the control group and carnosine group, but in the steroid group appeared dense nuclear opacity, while both two carnosine-treated groups came out visible demarcation between nuclear and cortical regions on 7 days. A decrease in the activity of Na+-K+ATPase was found in the lens of the steroid group. On 3, 5, 7 days, Na+-K+ATPase activity decreased 22.34% (P =0.002), 47.98% (P <0.001), 75.37%(P <0.001) compared with that at 1 day, respectively. In the carnosine group, the activity of Na+-K+ATPase remained at the level of the control throughout the 7-day incubation, indicating that carnosine itself did not interfere with the original lens enzyme activity. In the lower concentration carnosine-treated group, on 3, 5, 7 days, the activity of Na+-K+ATPase increased 10.8% (P <0.05), 44.6% (P <0.01), 57.4% (P <0.01) of control activity, respectively. In the higher concentration carnosine-treated group, the activity of Na+-K+ ATPase increased 11.3% (P <0.05), 45.7% (P <0.01), 57.6% (P <0.01), respectively on 3, 5, 7 days. The activity of Na+-K+ATPase in both two carnosine-treated groups were only 6.7% and 6.5% lower than that of the control group after 7-day incubation. After the 7-day incubation, the Na+-K+ ATPase activity of the lenses in the steroid group decreased significantly compared with carnosine-treated groups(P ＜0.01). CONCLUSION: Carnosine prevents the cataract formation induced by a glucocorticoid, and significantly inhibits the inactivation of Na+-K+ATPase induced by a glucocorticoid.}