[Study of the neuroprotective effects of carnosine in an experimental model of focal cerebral ischemia/reperfusion]

Biomed Khim. 2018 Aug;64(4):344-348. doi: 10.18097/PBMC20186404344.
[Article in Russian]

Abstract

Oxidative stress is one of the key factors in brain tissue damage in ischemia, which indicates the appropriateness of using antioxidants under these conditions. One of the promising antioxidants for the therapy of ischemic stroke is the natural dipeptide carnosine. The neuroprotective effect of dietary carnosine administration was investigated in an experimental model of focal cerebral ischemia/reperfusion in Wistar rats. Animals received carnosine with a diet at a daily dose of 150 mg/kg for 7 days before temporary occlusion of the middle cerebral artery (MCA), performed for 60 min. At 24 h after the onset of ischemia the effect of carnosine on the area of the necrotic core was evaluated in animals. In brain tissue of animals the content of malondialdehyde (MDA), protein carbonyls (PC), total antioxidant capacity (TAC), total activity of superoxide dismutase (SOD), glutathione peroxidase (GP), catalase (CAT) and glutathione transferase (GT), content of isoprostanes and cytokines were measured. Carnosine significantly reduced the infarct size. Carnosine also increased TAC and reduced the level of MDA and isoprostanes in brain tissue. Influence of carnosine on other parameters was not detected. Thus carnosine consumed prophylactically with the diet for 7 days before the induction of ischemia by means of MCA occlusion in rats provides the direct neuroprotective effect, retains high antioxidant activity of brain tissue, reduces the level of oxidative damage markers (MDA and isoprostanes) but does not have any effect on the activity of antioxidant enzyme systems and production of cytokines in brain tissue.

Odnim iz kliuchevykh faktorov povrezhdeniia tkani golovnogo mozga pri ishemii iavliaetsia okislitel'nyĭ stress, chto sluzhit obosnovaniem dlia primeneniia antioksidantov v étikh usloviiakh. Issledovali neĭroprotektornoe deĭstvie prirodnogo dipeptida karnozina pri ego kursovom profilakticheskom prieme pri éksperimental'noĭ fokal'noĭ ishemii s reperfuzieĭ golovnogo mozga u krys linii Wistar. Zhivotnye poluchali karnozin s ratsionom v sutochnoĭ doze 150 mg/kg v techenie 7 dneĭ pered 60 min okkliuzieĭ srednemozgovoĭ arterii (SMA). Cherez 24 ch posle nachala ishemii u zhivotnykh otsenivali ploshchad' ochaga nekroza. V tkani mozga zhivotnykh opredeliali soderzhanie malonovogo dial'degida (MDA), karbonil'nykh proizvodnykh belkov (KPB), obshchuiu antioksidantnuiu aktivnost' (OAA), obshchuiu aktivnost' superoksiddismutazy (SOD), glutationperoksidazy (GP), katalazy (KAT), glutationtransferazy (GT), kontsentratsiiu izoprostanov i tsitokinov. Karnozin znachimo umen'shal ploshchad' nekroticheskogo ochaga pri ishemii, a takzhe uvelichival OAA i snizhal uroven' MDA i izoprostanov v tkani mozga. Poluchennye rezul'taty svidetel'stvuiut o tom, chto pri profilakticheskom prieme v sostave pishchevogo ratsiona v techenie 7 dneĭ do ishemii, vyzvannoĭ okkliuzieĭ SMA u krys, karnozin okazyvaet priamoe neĭroprotektornoe deĭstvie, sokhraniaet vysokuiu antioksidantnuiu aktivnost' tkani mozga, snizhaet uroven' markerov okislitel'nogo povrezhdeniia (MDA i izoprostanov), no ne vliiaet na aktivnost' fermentov sistemy antioksidantnoĭ zashchity i produktsiiu tsitokinov v tkani mozga.

Keywords: brain ischemia; carnosine; inflammation; neuroprotection; oxidative stress.

MeSH terms

  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / therapeutic use*
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / metabolism
  • Brain Ischemia / pathology
  • Carnosine / administration & dosage
  • Carnosine / therapeutic use*
  • Disease Models, Animal
  • Male
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / therapeutic use*
  • Oxidative Stress / drug effects
  • Rats, Wistar
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*

Substances

  • Antioxidants
  • Neuroprotective Agents
  • Carnosine