Lovastatin decreases the synthesis of inflammatory mediators in the hippocampus and blocks the hyperthermia of rats submitted to long-lasting status epilepticus

Gouveia, Telma Luciana Furtado; Silva, Michele Juliana Vieira; Bandeira, Tatiane de Aquino; Perosa, Sandra Regina; Argañaraz, Enrique R.; Silva, Marcelo de Paula; Araújo, Ticiana Vasques de; Frangiotti, Maria Isabel Berzaghi; Amado, Débora; Cavalheiro, Ésper A.; Silva, José António; Naffah-Mazzacoratti, Maria da Graça

doi:10.1016/j.yebeh.2010.10.001

Cited by 28 publications

(23 citation statements)

References 70 publications

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“…[22] Although the exact role of lovastatin in the treatment of MDD is not known, there is a growing body of literature about the association of some cytokines and depression symptoms. [9,10] In addition, statins may decrease the activity of IDO. [2] IL-6 and IL-8 levels are associated with current depressive symptoms.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Augmentation of Fluoxetine With Lovastatin for Treating Major Depressive Disorder, a Randomized Double-Blind Placebo Controlled-Clinical Trial

Ghanizadeh

Hedayati

2013

Depress Anxiety

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Section: Discussionmentioning

confidence: 99%

“…[5] The levels of IL-6 and tumor necrosis factor (TNF-α) in depressed smoker are higher than nondepressed smokers. [9,10] Furthermore, statins may decrease the activity of indoleamine (2,3)-dioxygenase (IDO). Simvastatin [7] and atrovastatin, [8] which are statins, inhibit inflammation through decreasing IL-β and TNF-α levels.…”

Section: Introductionmentioning

confidence: 99%

Augmentation of Fluoxetine With Lovastatin for Treating Major Depressive Disorder, a Randomized Double-Blind Placebo Controlled-Clinical Trial

Ghanizadeh

Hedayati

2013

Depress Anxiety

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“…Previous studies have investigated effects of two statins, atorovastatin [35], [46], [72] and lovastatin [73], [74], on neuronal protection during epileptogenesis and attenuating seizure behavior in various animal models, including pentylentetrazole-kindled rats, quinolinic acid-induced seizure, pilocarpine-induced status epileptic and kainic-acid induced seizure. A very recent study has compared 9 statins by analyzing several parameters that could be related to neuroprotection and suggests that simvastatin presents the best characteristics for preventing neurodegenerative conditions, due to its high BBB penetration capacity and cholesterol lowering effect on neurons [29].…”

Section: Discussionmentioning

confidence: 99%

Administration of Simvastatin after Kainic Acid-Induced Status Epilepticus Restrains Chronic Temporal Lobe Epilepsy

et al. 2011

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In this study, we examined the effect of chronic administration of simvastatin immediately after status epilepticus (SE) on rat brain with temporal lobe epilepsy (TLE). First, we evaluated cytokines expression at 3 days post KA-lesion in hippocampus and found that simvastatin-treatment suppressed lesion-induced expression of interleukin (IL)-1β and tumor necrosis factor-α (TNF-α). Further, we quantified reactive astrocytosis using glial fibrillary acidic protein (GFAP) staining and neuron loss using Nissl staining in hippocampus at 4–6 months after KA-lesion. We found that simvastatin suppressed reactive astrocytosis demonstrated by a significant decrease in GFAP-positive cells, and attenuated loss of pyramidal neurons in CA3 and interneurons in dentate hilar (DH). We next assessed aberrant mossy fiber sprouting (MFS) that is known to contribute to recurrence of spontaneous seizure in epileptic brain. In contrast to the robust MFS observed in saline-treated animals, the extent of MFS was restrained by simvastatin in epileptic rats. Attenuated MFS was related to decreased neuronal loss in CA3 and DH, which is possibly a mechanism underlying decreased hippocampal susceptibility in animal treated with simvastatin. Electronic encephalography (EEG) was recorded during 4 to 6 months after KA-lesion. The frequency of abnormal spikes in rats with simvastatin-treatment decreased significantly compared to the saline group. In summary, simvastatin treatment suppressed cytokines expression and reactive astrocytosis and decreased the frequency of discharges of epileptic brain, which might be due to the inhibition of MFS in DH. Our study suggests that simvastatin administration might be a possible intervention and promising strategy for preventing SE exacerbating to chronic epilepsy.

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“…Since many neurologic disorders are affected by lipid metabolism and inflammation, statins are being investigated for their possible neuroprotective properties with regard to diseases such as persistent seizures and Alzheimer's disease [11–13]. In the field of orthopedics, statins are being investigated as a possible solution to the destruction of cartilage by inflammation, as seen in osteoarthritis.…”

Section: Pleiotropic Effects Of Statinsmentioning

confidence: 99%

Novel applications of statins for bone regeneration

Shah

Werlang

Kasper

et al. 2014

National Science Review

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The use of statins for bone regeneration is a promising and growing area of research. Statins, originally developed to treat high cholesterol, are inhibitors of the enzyme 3-hydroxy-3-methylglutaryl, the rate-limiting enzyme of the mevalonate pathway. Because the mevalonate pathway is responsible for the synthesis of a wide variety of important biochemical molecules, including cholesterol and other isoprenoids, the effects of statins are pleiotropic. In particular, statins can greatly affect the process of bone turnover and regeneration via effects on important cell types, including mesenchymal stem cells, osteoblasts, endothelial cells, and osteoclasts. Statins have also been shown to have anti-inflammatory and antimicrobial properties that may be useful since infection can derail normal bone healing. This review will explore the pleiotropic effects of statins, discuss the current use of statins for bone regeneration, particularly with regard to biomaterials-based controlled delivery, and offer perspectives on the challenges and future directions of this emerging area of bone tissue engineering.

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Lovastatin decreases the synthesis of inflammatory mediators in the hippocampus and blocks the hyperthermia of rats submitted to long-lasting status epilepticus

Cited by 28 publications

References 70 publications

Augmentation of Fluoxetine With Lovastatin for Treating Major Depressive Disorder, a Randomized Double-Blind Placebo Controlled-Clinical Trial

Augmentation of Fluoxetine With Lovastatin for Treating Major Depressive Disorder, a Randomized Double-Blind Placebo Controlled-Clinical Trial

Administration of Simvastatin after Kainic Acid-Induced Status Epilepticus Restrains Chronic Temporal Lobe Epilepsy

Novel applications of statins for bone regeneration

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