Effect of policosanol on cerebral ischemia in Mongolian gerbils.
Policosanol is a mixture of higher aliphatic primary alcohols isolated from sugar cane wax, whose main component is octacosanol. An inhibitory effect of policosanol on platelet aggregation and cerebral ischemia in animal models has been reported. Thus, the objective of the present study was to evaluate the effect of policosanol on cerebral ischemia induced by unilateral carotid ligation and bilateral clamping and recirculation in Mongolian gerbils. Policosanol (200 mg/kg) administered immediately after unilateral carotid ligation and at 12- or 24-h intervals for 48 h significantly inhibited mortality and clinical symptoms when compared with controls, whereas lower doses (100 mg/kg) were not effective. Control animals showed swelling (tissue vacuolization) and necrosis of neurons in all areas of the brain studied (frontal cortex, hippocampus, striatum and olfactory tubercle), showing a similar injury profile. In the group treated with 200 mg/kg policosanol swelling and necrosis were significantly reduced when compared with the control group. In another experimental model, comparison between groups showed that the brain water content of control gerbils (N = 15) was significantly higher after 15 min of clamping and 4 h of recirculation than in sham-operated animals (N = 13), whereas policosanol (200 mg/kg) (N = 19) significantly reduced the edema compared with the control group, with a cerebral water content identical to that of the sham-operated animals. cAMP levels in the brain of control-ligated Mongolian gerbils (N = 8) were significantly lower than those of sham-operated animals (N = 10). The policosanol-treated group (N = 10) showed significantly higher cAMP levels (2.68 pmol/g of tissue) than the positive control (1.91 pmol/g of tissue) and similar to those of non-ligated gerbils (2.97 pmol/g of tissue). In conclusion, our results show an anti-ischemic effect of policosanol administered after induction of cerebral ischemia, in two different experimental models in Mongolian gerbils, suggesting a possible therapeutic effect in cerebral vascular disorders.
Molina
V
V
Department of Pharmacology, Center of Natural Products, National Center of Scientific Research, Havana, Cuba.
Arruzazabala
M L
ML
Carbajal
D
D
Valdés
S
S
Noa
M
M
Más
R
R
Fraga
V
V
Menéndez
R
R
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D003250:Constriction; D000242:Cyclic AMP / Q000032:analysis*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005233:Fatty Alcohols / Q000627:therapeutic use*; D005260:Female; D005849:Gerbillinae; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*
D005233:Fatty Alcohols; D010975:Platelet Aggregation Inhibitors; C080710:policosanol; D000242:Cyclic AMP