Hyperhomocysteinemia increases damage on brain slices exposed to in vitro model of oxygen and glucose deprivation: prevention by folic acid.
In the present study we evaluate the effects of homocysteine on cellular damage using hippocampal slices from Wistar rats exposed to oxygen and glucose deprivation (OGD, followed by reoxygenation), an in vitro model of hypoxic-ischemic events. For chronic treatment, we induced elevated levels of homocysteine in blood (500 microM), comparable to those of human homocystinuria, and in brain (60 nmol/g wet tissue) of young rats by subcutaneous injections of homocysteine (0.3-0.6 micromol/g of body weight), twice a day with 8 h intervals, from the 6 th to the 28 th postpartum day and controls received saline. Rats were sacrificed 1, 3 or 12 h after the last injection. For acute treatment, 29-day-old rats received one single injection of homocysteine (0.6 micromol homocysteine/g body weight) or saline and were sacrificed 1h later. In another set of experiments rats were pretreated with Vitamins E (40 mg/kg) and C (100 mg/kg) or folic acid (5 mg/kg) during 1 week; 12 h after the last administration they received a single injection of homocysteine or saline and were sacrificed 1 h later. Results showed that both chronic (1 h after homocysteine administration) and acute hyperhomocysteinemia increased the cellular damage measured by LDH released to de incubation medium, suggesting an increase of tissue damage caused by OGD. Pretreatment with folic acid completely prevented the damage caused by acute hyperhomocysteinemia, whereas Vitamin E just partially prevented such effect. These findings may be relevant to explain, at least in part, the higher susceptibility of hyperhomocysteinemic patients to be susceptible to ischemic events and point to a possible preventive treatment.
Tagliari
Bárbara
B
Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil.
Zamin
Lauren L
LL
Salbego
Christianne G
CG
Netto
Carlos Alexandre
CA
Wyse
Angela T S
AT
D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005492:Folic Acid / Q000627:therapeutic use*; D005947:Glucose / Q000172:deficiency*; D006710:Homocysteine / Q000008:administration & dosage / Q000009:adverse effects; D020138:Hyperhomocysteinemia / Q000139:chemically induced / Q000150:complications*; D000860:Hypoxia; D020925:Hypoxia-Ischemia, Brain / Q000517:prevention & control*; D066298:In Vitro Techniques; D045022:Lactate Dehydrogenases / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014801:Vitamin A / Q000627:therapeutic use; D014803:Vitamin B Complex / Q000627:therapeutic use*
D006710:Homocysteine; D014801:Vitamin A; D014803:Vitamin B Complex; D005492:Folic Acid; D045022:Lactate Dehydrogenases; D005947:Glucose