Neuroprotector effect of p,p'‐methoxyl‐diphenyl diselenide in a model of sporadic dementia of Alzheimer's type in mice: contribution of antioxidant mechanism

Abstract

The present study investigated whether the antioxidant activity of p,p'-methoxyl-diphenyl diselenide [(MeOPhSe)(2)] is involved in its protective effect against cognitive impairment induced by streptozotocin (STZ) in a model of sporadic dementia of Alzheimer's type (SDAT). Swiss mice were treated with STZ or vehicle [2 µl of 2·5 mg ml(-1) solution; intracerebroventricularly (i.c.v.)] twice, 48 h apart. (MeOPhSe)(2) (25 mg kg(-1)) or vehicle was orally administered 30 min prior to each STZ treatment. Neuroprotector effect of (MeOPhSe)(2) on the behavioral performance of mice on spatial recognition memory consolidation was investigated in the Y-maze test. After that, mouse brains were removed for measuring antioxidant parameters. (MeOPhSe)(2) protected against the impairment in learning and memory caused by i.c.v. administration of STZ in mice. (MeOPhSe)(2) protected against the increase in reactive species and the reduction of glutathione levels, as well as, the increase in superoxide dismutase and glutathione S-transferase activities caused by STZ in whole brain. These results suggest that antioxidant property is involved, at least in part, in the neuroprotective effect of (MeOPhSe)(2) on SDAT induced by STZ in mice.

Therapeutic effect of organoselenium dietary supplementation in a sporadic dementia of Alzheimer's type model in rats

“…These results suggest that the antioxidant property could be involved in the (MeOPhSe) 2 neuroprotective effect on SDAT induced by STZ in rats. Accordingly, the neuroprotective effect of the antioxidant (MeOPhSe) 2 was reported [19].…”

“…There have also been data indicating the involvement of oxidative stress in STZ-induced SDAT model [12,23]. Based on these positive results [19,20], we planned this study to investigate the therapeutic effect of (MeOPhSe) 2 against STZ-induced SDAT model. The involvement of AChE activity, deficit in cerebral energy metabolism, and oxidative and nitrosative stress in the therapeutic effect of (MeOPhSe) 2 in the cognitive impairment induced by STZ was examined.…”

“…Moreover, preadministration of p,p'-methoxyl-diphenyl diselenide [(MeOPhSe) 2 ], a substituted analogue of (PhSe) 2 , improves memory of mice in the model of sporadic dementia of Alzheimer's type (SDAT) induced by intracerebroventricular (icv) injection of streptozotocin (STZ) [19,20]. Icv injection of STZ to rodents has been reported as an appropriate SDAT model, characterized by an impairment of memory [21].…”

What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer’s disease, about the therapeutic strategies in Alzheimer’s research

“…), 21-day treatment alone, while its combination with subeffective dose of sesamol (4 mg/kg) potentiated its protective effect (Misra et al 2011), confirming that modulation of nitrite signalling and the oxide-inflammatory cascade might provide therapeutic effects in an AD condition. Selenium (Se), a nutritionally essential trace element with known antioxidant potential, protects the brain from oxidative damage in various models of neurodegeneration As already mentioned, neuroprotective effect of organoselenium (MeOPhSe)(2) administered orally (25 mg/kg) 30 min prior to STZ-icv injection in mice was manifested in cognitive improvement in the Y-maze test associated with an anticholinesterase efficacy (Pinton et al 2010) but additional experiments demonstrated that its neuroprotection in the STZ-icv model is due to its antioxidant activity as well (Pinton et al 2011). Pretreatment supplementation with sodium selenite, a salt of Se (0.1 mg/kg p.o.…”

An Overview of Target Specific Neuro-Protective and Neuro-Restorative Strategies

“…Recent experimental studies using a wide range of antioxidants including P-P methoxydiphenyl diselenide (Pinton et al, 2011), S allyl cysteine (Javed et al, 2011), conjugates of ibuprofen and glutathione (Pinnen et al, 2011), tirilazad , Ibuprofen and lipoic acid (Distefano et al, 2010), and chlorogenic acid (Kwon et al, 2010), have shown neuroprotective effects in animal models of AD. On the other hand mitochondria specific antioxidants such as acetyl-L-carnitine and R-alpha lipoic acid have been suggested to be beneficial for treatments for AD (Palacios et al, 2011).…”