Evaluation of liposomal carnosine in adjuvant arthritis

Slovák, Lukáš; Poništ, Silvester; Федорова, Т. Н.; Logvinenko, Anna; Levacheva, I. S.; Samsonova, Olga; Bakowsky, Udo; Pašková, Ľudmila; Čavojský, Tomáš; Tsiklauri, Lia; Bauerová, Katarína

doi:10.4149/gpb_2017014

Cited by 6 publications

(5 citation statements)

References 35 publications

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“…Therefore, a potential strategy to enhance carnosine bioavailability is to transport the molecule by means of drug delivery systems able to prevent the hydrolysis operated by serum carnosinase [ 129 ]. The two main strategies reported in the literature are to include carnosine in metallic nanoparticles [ 130 , 131 , 132 ] or vesicular systems [ 133 , 134 , 135 , 136 ].…”

Section: Human Serum Carnosinase As a Druggable Targetmentioning

confidence: 99%

State of the Art in the Development of Human Serum Carnosinase Inhibitors

Regazzoni

2024

Molecules

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Human serum carnosinase is an enzyme that operates the preferential hydrolysis of dipeptides with a C-terminus histidine. Only higher primates excrete such an enzyme in serum and cerebrospinal fluid. In humans, the serum hydrolytic rate has high interindividual variability owing to gene polymorphism, although age, gender, diet, and also diseases and surgical interventions can modify serum activity. Human genetic diseases with altered carnosinase activity have been identified and associated with neurological disorders and age-related cognitive decline. On the contrary, low peripheral carnosinase activity has been associated with kidney protection, especially in diabetic nephropathy. Therefore, serum carnosinase is a druggable target for the development of selective inhibitors. However, only one molecule (i.e., carnostatine) has been discovered with the purpose of developing serum carnosinase inhibitors. Bestatin is the only inhibitor reported other than carnostatine, although its activity is not selective towards serum carnosinase. Herein, we present a review of the most critical findings on human serum carnosinase, including enzyme expression, localization and substrate selectivity, along with factors affecting the hydrolytic activity, its implication in human diseases and the properties of known inhibitors of the enzyme.

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Section: Human Serum Carnosinase As a Druggable Targetmentioning

confidence: 99%

State of the Art in the Development of Human Serum Carnosinase Inhibitors

Regazzoni

2024

Molecules

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“…Anti-inflammatory and antioxidant effects of liposomal and non-liposomal carnosine in adjuvant arthritis were compared by Slovák et al [ 114 ]. Both forms were able to decrease plasmatic levels of interleukin (IL)-1β, matrix metalloproteinase-9, and monocyte chemoattractant protein-1 (MCP-1), but only liposomal carnosine significantly reduced the levels of MCP-1.…”

Section: Increasing Carnosine Bioavailability Through Dds And/or Chem...mentioning

confidence: 99%

“…Reduced oxidative stress and inflammation [114] Elastic liposomes EL encapsulated with carnosine represent a promising strategy to enhance the transport into the brain, protecting the dipeptide against enzymatic hydrolysis.…”

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confidence: 99%

The Therapeutic Potential of Novel Carnosine Formulations: Perspectives for Drug Development

et al. 2023

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Carnosine (beta-alanyl-L-histidine) is an endogenous dipeptide synthesized via the activity of the ATP-dependent enzyme carnosine synthetase 1 and can be found at a very high concentration in tissues with a high metabolic rate, including muscles (up to 20 mM) and brain (up to 5 mM). Because of its well-demonstrated multimodal pharmacodynamic profile, which includes anti-aggregant, antioxidant, and anti-inflammatory activities, as well as its ability to modulate the energy metabolism status in immune cells, this dipeptide has been investigated in numerous experimental models of diseases, including Alzheimer’s disease, and at a clinical level. The main limit for the therapeutic use of carnosine is related to its rapid hydrolysis exerted by carnosinases, especially at the plasma level, reason why the development of new strategies, including the chemical modification of carnosine or its vehiculation into innovative drug delivery systems (DDS), aiming at increasing its bioavailability and/or at facilitating the site-specific transport to different tissues, is of utmost importance. In the present review, after a description of carnosine structure, biological activities, administration routes, and metabolism, we focused on different DDS, including vesicular systems and metallic nanoparticles, as well as on possible chemical derivatization strategies related to carnosine. In particular, a basic description of the DDS employed or the derivatization/conjugation applied to obtain carnosine formulations, followed by the possible mechanism of action, is given. To the best of our knowledge, this is the first review that includes all the new formulations of carnosine (DDS and derivatives), allowing a decrease or complete prevention of the hydrolysis of this dipeptide exerted by carnosinases, the simultaneous blood–brain barrier crossing, the maintenance or enhancement of carnosine biological activity, and the site-specific transport to different tissues, which then offers perspectives for the development of new drugs.

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“…Adjuvant arthritis (AA) was induced by intradermal injection of Mycobacterium butyricum in incomplete Freund's adjuvant to male Lewis rats [36,37]. The experiment included healthy control animals (HC), arthritic animals (AA), and arthritic animals with administration of CoQ 10 (liquid liposomal CoQ 10 -LiQSorb ® ) in the oral daily dose of 100 mg/kg b.w.…”

Section: Experimental Design Of Adjuvant Arthritis With Administratiomentioning

confidence: 99%

“…(1) Not treated control groups (HC) (2) Arthritic animals not treated with HA (AA) Adjuvant arthritis was induced by a single intradermal injection of heat-inactivated Mycobacterium butyricum [36,37]. Blood was collected to obtain plasma and erythrocytes.…”

Section: Experimental Design Of Adjuvant Arthritis With Administratiomentioning

confidence: 99%

The Role of Endogenous Antioxidants in the Treatment of Experimental Arthritis

Bauerová¹,

Kucharská²,

Poništ³

et al. 2019

Antioxidants

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The pathogenesis of rheumatoid arthritis is poorly understood; however, elevated oxidative stress has been described to be involved. In this chapter, we present experiments with endogenous molecules bearing antioxidative properties. In our studies, we used male Lewis rats, and the arthritis was induced with Mycobacterium butyricum. In the first experiment, we tested coenzyme Q 10 (CoQ 10) in the oral daily dose of 100 mg/kg b.w. Markers of inflammation and total antioxidant status were corrected in the group supplemented. CoQ 10 treatment significantly improved concentrations of the investigated endogenous antioxidants. Further as an important fact, we consider a good bioavailability of used CoQ 10 formulation which was confirmed by increased CoQ concentrations in plasma, tissue, and mitochondria from skeletal muscles. In the second study, we describe the results with hyaluronic acid (HA) administered in oral daily doses of 0.5 mg and 5 mg/kg b.w. and of different molecular weights (0.43, 0.99, and 1.73 MDa). A notable antioxidative effect of HA was assessed: its administration increased the activities of antioxidant enzymes (superoxide dismutase and glutathione peroxidase) in erythrocytes and total antioxidant capacity of plasma and reduced the marker of oxidative damage to lipids-plasmatic lipid hydroperoxides. HA with the highest molecular weight showed the most significant effect.

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Evaluation of liposomal carnosine in adjuvant arthritis

Cited by 6 publications

References 35 publications

State of the Art in the Development of Human Serum Carnosinase Inhibitors

State of the Art in the Development of Human Serum Carnosinase Inhibitors

The Therapeutic Potential of Novel Carnosine Formulations: Perspectives for Drug Development

The Role of Endogenous Antioxidants in the Treatment of Experimental Arthritis

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