engleski

Overview of the effectiveness of multifunctional antioxidant compounds in the streptozotocin-induced animal model of sporadic Alzheimer's disease

Objectives: Oxidative stress in the brain has been emphasized as probably one of the earliest features in the pathogenesis of the Alzheimer's disease (AD). Various antioxidant compounds have shown variable efficacy in clinical trials. Failure to accurately predict clinical efficacy of such drugs can result also from inappropriate animal model used in preclinical drug testing. Rats treated intracerebroventricularly with a betacytotoxic drug streptozotocin (STZ-icv) have been recently proposed as a non-transgenic animal model for sporadic AD (sAD). We aimed to perform a survey of the literature data on preclinical therapeutic effectiveness of compounds with antioxidant activity in the STZ-icv rat model of sAD. Methods: Therapeutic effectiveness of the compounds with a predominant antioxidant activity in the STZ-icv animal model has been assessed by means of PUBMED search for the work published until April 2012. Results: Twenty-six experiments tested 20 compounds (excluding Chinese herbal drugs) with predominant antioxidant activity in the STZ-icv animal model. All but one experiment demonstrated therapeutic activity on the cognitive deficits (25/26), additionally improving cholinergic neurotransmission (15/25), brain insulin signalling or acting anti-inflammatory. Antioxidant treatment was initiated mostly (19/25) after the STZ-icv treatment. One third of the compounds demonstrated also some clinical effectiveness but half of the compounds have not been tested clinically. Conclusions: Antioxidant compounds seem to demonstrate less variable effectiveness in the STZ-icv model than in clinical AD, possibly due to their additional pharmacodynamic activities, the diversity of which might be of greater importance for the human sAD pathophysiology. Supported by DAAD and MZOS.

antioxidant; streptozotocin; Alzheimer's disease

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