title: Neuroprotective effects of p-tyrosol after the global cerebral ischemia in rats.
abstract: BACKGROUND
  Salidroside is a biologically active compound derived from Rhodiola rosea L. Studies showed that salidroside after i.v. injection is extensively metabolized to p-tyrosol and only trace amounts of salidroside are found in the brain tissue.
  
  
  OBJECTIVE
  The aim of the study was to investigate the neuroprotective effects of p-tyrosol in the global cerebral ischemia-reperfusion (GCI) model.
  
  
  METHODS
  A total of 103 Wistar rats were assigned to groups of sham-operated (n=10), control (n=42), p-tyrosol-treated (n=36), and pentoxifylline-treated (n=15) animals. The rats of control, p-tyrosol-treated, and pentoxifylline-treated groups received intravenously 0.9% NaCl solution, 2% solution of p-tyrosol in doses of 5mg/kg, 10mg/kg, and 20mg/kg, and pentoxifylline in a dose of 100mg/kg, respectively, daily for 5 days. Rats were examined at days 1, 3, and 5 after GCI. After evaluation of neurological deficit, animals were euthanized for morphological and biochemical characterization.
  
  
  METHODS
  Rats of control, p-tyrosol-treated, and pentoxifylline-treated groups were exposed to three-vessel model of GCI. Neurological deficit, numeric density of neurons in hippocampal CA1 region, and percentage of neurons with focal and total chromatolysis were studied. Biochemical study assessed contents of conjugated dienes and fluorescent products in brain homogenate.
  
  
  RESULTS
  In control group, only 50.0% of rats survived by day 5 after the GCI; 38.1% of survived animals had severe neurologic deficit. In brain tissue of PTX-treated rats, the levels of diene conjugates and fluorescent products were 79% and 73%, respectivley, at day 5 compared with control. Differences in diene conjugates were statistically significant compared with control. The survival rate of animals treated with 20mg/kg p-tyrosol was 82.3% at day 5 after GCI. In p-tyrosol-treated GCI rats, the numeric density of neurons in the hippocampal CA1 region was higher by 31% compared with control. The percentage of neurons with focal and total chromatolysis decreased by 27% and 43%, respectively. At day 5 after GCI, the levels of conjugated dienes and fluorescent products were significantly lower (by 37% and 45%, respectively) in group of animals treated with 20mg/kg p-tyrosol compared with control. Moderate neuroprotective effects of 5mg/kg p-tyrosol administration were documented only at day 5 after GCI. In case of 10mg/kg p-tyrosol administration, neuroprotection was documented sooner: at day 1 or 3 after GCI. However, administration of 5 and 10mg/kg p-tyrosol did not affect animal survival.
  
  
  CONCLUSIONS
  Course administration of intravenous p-tyrosol in a dose of 20mg/kg increased survival, reduced neurological deficit after GCI, attenuated neuronal damage in the hippocampus, and attenuated lipid peroxidation in brain tissue in animals subject to GCI with reperfusion.
authors.affiliation: Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States ; RASA Center in Tomsk, Tomsk Polytechnic University, 30 Lenin Street, Tomsk 634050, Russia.
authors.forename: Dmitriy N
authors.initials: DN
authors.lastname: Atochin
authors.affiliation: Federal State Budgetary Scientific Institution "E.D. Goldberg Institute of Pharmacology and Regenerative Medicine", 3 Lenin Street, Tomsk 634028, Russia.
authors.forename: Galina A
authors.initials: GA
authors.lastname: Chernysheva
authors.affiliation: Federal State Budgetary Scientific Institution "E.D. Goldberg Institute of Pharmacology and Regenerative Medicine", 3 Lenin Street, Tomsk 634028, Russia.
authors.forename: Vera I
authors.initials: VI
authors.lastname: Smolyakova
authors.affiliation: Siberian State Medical University, 2 Moscowsky Trakt 634050, Tomsk, Russia.
authors.forename: Anton N
authors.initials: AN
authors.lastname: Osipenko
authors.affiliation: Siberian State Medical University, 2 Moscowsky Trakt 634050, Tomsk, Russia.
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Logvinov
authors.affiliation: Siberian State Medical University, 2 Moscowsky Trakt 634050, Tomsk, Russia.
authors.forename: Anna A
authors.initials: AA
authors.lastname: Zhdankina
authors.affiliation: Institute for Problems of Chemical and Energetic Technologies, Siberian Branch of the Russian Academy of Sciences, 1 Socialisticheskaya Street, Biysk, Russia.
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Sysolyatin
authors.affiliation: Institute for Problems of Chemical and Energetic Technologies, Siberian Branch of the Russian Academy of Sciences, 1 Socialisticheskaya Street, Biysk, Russia.
authors.forename: Yuri A
authors.initials: YA
authors.lastname: Kryukov
authors.affiliation: Federal State Budgetary Scientific Institution "Research Institute for Cardiology", 111a Kievskaya Street, Tomsk 634012, Russia; RASA Center in Tomsk, Tomsk Polytechnic University, 30 Lenin Street, Tomsk 634050, Russia.
authors.forename: Yana
authors.initials: Y
authors.lastname: Anfinogenova
authors.affiliation: Siberian State Medical University, 2 Moscowsky Trakt 634050, Tomsk, Russia.
authors.forename: Tatiana M
authors.initials: TM
authors.lastname: Plotnikova
authors.affiliation: Federal State Budgetary Scientific Institution "E.D. Goldberg Institute of Pharmacology and Regenerative Medicine", 3 Lenin Street, Tomsk 634028, Russia. Electronic address: mbp2001@mail.ru.
authors.forename: Mark B
authors.initials: MB
authors.lastname: Plotnikov
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D002545:Brain Ischemia / Q000473:pathology / Q000517:prevention & control* / Q000523:psychology; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000473:pathology; D002544:Cerebral Infarction / Q000473:pathology / Q000517:prevention & control; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010431:Pentoxifylline / Q000494:pharmacology; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control* / Q000523:psychology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D018696:Neuroprotective Agents; D014665:Vasodilator Agents; C011867:4-hydroxyphenylethanol; D010626:Phenylethyl Alcohol; D010431:Pentoxifylline
keywords: Antioxidant effect; Global cerebral ischemia; Neuroprotective effect; Pentoxifylline; p-tyrosol