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Tamoxifen Protects Rat Brains in Acute Stroke

Neuroprotection occurs via antioxidant mechanism

MONDAY, Jan. 14 (HealthDay News) -- Tamoxifen appears to exert neuroprotective effects via an antioxidant mechanism in an animal model of acute stroke, according to research published in Endocrinology in January.

Chandramohan Wakade, Ph.D., and Mohammad M. Khan, of the Medical College of Georgia in Augusta, and colleagues induced cerebral ischemia in ovariectomized rats by occluding the middle cerebral artery. They subsequently compared superoxide ion production and the activation state of 31 different kinases in the brains of tamoxifen-treated rats versus placebo-treated rats.

The researchers found that tamoxifen significantly decreased superoxide ion production, oxidative damage to proteins and DNA, and activation of proapoptotic caspase-3. In addition, tamoxifen enhanced production of manganese superoxide dismutase (MnSOD), a scavenger of superoxide ion, suggesting a potential mechanism for the antioxidant effects of tamoxifen.

"In conclusion, the current study provides evidence that tamoxifen protects the brain against cerebral ischemia via an antioxidant mechanism that involves enhancement of MnSOD expression, with correlated reduction of superoxide anion production, oxidative damage and caspase-3 activation in the injured cortex. It is further proposed that suppression of oxidative stress by tamoxifen leads to an attenuation, at least in part, of pro-death ERK signaling in the cortex penumbra, thereby facilitating neuronal survival," the authors write.

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