Dual Effect of Carnosine on ROS Formation in Rat Cultured Cortical Astrocytes

• Published in: Molecular neurobiology Vol. 61; no. 7; pp. 4908 - 4922
• Main Authors: Diniz, Fabiola, Parmeggiani, Belisa, Brandão, Gabriela, Ferreira, Bruna Klippel, Teixeira, Monique Fonseca, Streck, Emilio Luiz, Olivera-Bravo, Silvia, Barbeito, Luis Hector, Schuck, Patricia Fernanda, de Melo Reis, Ricardo Augusto, Ferreira, Gustavo Costa
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.07.2024; Springer Nature B.V
• Subjects: Animals; Animals, Newborn; Astrocytes; Astrocytes - drug effects; Astrocytes - metabolism; Biomedical and Life Sciences; Biomedicine; Carnosine; Carnosine - pharmacology; Cell Biology; Cells, Cultured; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Dizocilpine; Glutamic acid receptors; Glutamic acid receptors (ionotropic); Histidine; Hydrogen Peroxide; Membrane potential; Membrane Potential, Mitochondrial - drug effects; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; N-Methyl-D-aspartic acid receptors; Neonates; Neurobiology; Neurology; Neuroprotection; Neurosciences; Oxidants; Oxidation; Oxidation-Reduction - drug effects; Rats; Rats, Wistar; Reactive Oxygen Species - metabolism; Receptors, N-Methyl-D-Aspartate - metabolism; Superoxide anions; Thiobarbituric acid; Carnosinemia; Mitochondria; Reactive oxygen species; NMDA receptor; Imidazolic dipeptides
• ISSN: 0893-7648; 1559-1182; 1559-1182
• DOI: 10.1007/s12035-023-03880-0

Carnosine is composed of β-alanine and L-histidine and is considered to be an important neuroprotective agent with antioxidant, metal chelating, and antisenescence properties. However, children with serum carnosinase deficiency present increased circulating carnosine and severe neurological symptoms. We here investigated the in vitro effects of carnosine on redox and mitochondrial parameters in cultured cortical astrocytes from neonatal rats. Carnosine did not alter mitochondrial content or mitochondrial membrane potential. On the other hand, carnosine increased mitochondrial superoxide anion formation, levels of thiobarbituric acid reactive substances and oxidation of 2′,7′-dichlorofluorescin diacetate (DCF-DA), indicating that carnosine per se acts as a pro-oxidant agent. Nonetheless, carnosine prevented DCF-DA oxidation induced by H 2 O 2 in cultured cortical astrocytes. Since alterations on mitochondrial membrane potential are not likely to be involved in these effects of carnosine, the involvement of N-Methyl-D-aspartate (NMDA) receptors in the pro-oxidant actions of carnosine was investigated. MK-801, an antagonist of NMDA receptors, prevented DCF-DA oxidation induced by carnosine in cultured cortical astrocytes. Astrocyte reactivity induced by carnosine was also prevented by the coincubation with MK-801. The present study shows for the very first time the pro-oxidant effects of carnosine per se in astrocytes. The data raise awareness on the importance of a better understanding of the biological actions of carnosine, a nutraceutical otherwise widely reported as devoid of side effects.