Antidepressant-like effect of simvastatin in diabetic rats

ElBatsh, Maha M.

doi:10.1139/cjpp-2014-0560

Cited by 29 publications

(18 citation statements)

References 65 publications

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“…Turkish women who are susceptible to enhanced inflammation and autoimmune activation more than men (Onat and Can, ; Onat et al , 2016) support such a potential link, in view of reports that prolonged use of another group of drugs has been repeatedly documented to predict incident diabetes (Sattar et al , ; Culver et al , ; Wang et al , ). Interestingly, in experiments on rats, simvastatin administration exerted antidepressant‐like effects in diabetes‐induced rat groups, mediated by decreasing corticosterone levels, as compared with the control group (El Batsh, ). Collectively, the observations mentioned in the preceding texts indicate a possibility that requires further research on the issue whether antidepressant drug use may increase the risk of diabetes incidence in people with DeprS and on the circumstances of ethnicity and susceptibility to metabolic syndrome.…”

Section: Discussionmentioning

confidence: 99%

Sex‐dependent independent prediction of incident diabetes by depressive symptoms

Akbaş-Şimşek

Onat

Kaya

et al. 2016

Int J Geriat Psychiatry

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Section: Discussionmentioning

confidence: 99%

Sex‐dependent independent prediction of incident diabetes by depressive symptoms

Akbaş-Şimşek

Onat

Kaya

et al. 2016

Int J Geriat Psychiatry

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“…STT produced a synergistic effect on level of 5HT when given along with FLX (Figure 4). Recent reports also revealed the elevated level of 5HT and synergistic antidepressant activity after treatment with the STT 47,48. It can be explained that statins dose-dependently attenuate the activity of indoleamine 2,3-dioxygenase (IDO), which is an interferon γ-inducible enzyme that degrades tryptophan in the kynurenine pathway.…”

Section: Discussionmentioning

confidence: 99%

Simultaneous administration of fluoxetine and simvastatin ameliorates lipid profile, improves brain level of neurotransmitters, and increases bioavailability of simvastatin

Alasmari¹,

Ullah²,

Masoudi³

et al. 2017

JEP

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Simvastatin (STT), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, is widely prescribed for dyslipidemia, whereas fluoxetine (FLX) is the first-choice drug for the treatment of depression and anxiety. A recent report suggests that selective serotonin reuptake inhibitors can interact with the cytochrome P450 3A4 substrate, and another one suggests that STT enhances the antidepressant activity of FLX. However, the data are inconclusive. The present study was designed to explore the pharmacokinetic and pharmacodynamic consequences of coadministration of STT and FLX in experimental animals. For this, Wistar rats weighing 250±10 g were divided into four groups, including control, STT (40 mg/kg/day), FLX (20 mg/kg/day), and STT+FLX group, respectively. After the dosing period of 4 weeks, the animals were sacrificed, and the blood and brain samples were collected for the analysis of STT, simvastatin acid (STA), FLX, total cholesterol, triglyceride, high-density lipoprotein (HDL), 5-hydroxytryptamine, dopamine, and hydroxy indole acetic acid. It was found that the coadministration resulted in a significant increase in the bioavailability of STT in the plasma (41.8%) and brain (68.7%) compared to administration of STT alone (p<0.05). The maximum drug concentration (Cmax) of STT was also found to be increased significantly in the plasma and brain compared to that achieved after monotherapy (p<0.05). However, STT failed to improve the pharmacokinetics of FLX up to a significant level. The results of this study showed that the combined regimen significantly reduced the level of cholesterol and triglyceride and increased the level of HDL when compared to STT monotherapy. Furthermore, the coadministration of STT with FLX led to an elevated level of neurotransmitters in the brain (p<0.05). FLX increased the concentration of STT in the plasma and brain. The coadministration of these drugs also led to an improved lipid profile. However, in the long-term, this interaction may have a vital clinical importance because the increase in STT level may lead to life-threatening side effects associated with statins.

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“…As well as for the previous neurological disorders discussed so far, there are reported discrepancies about statins' effect in depression, with some studies reporting positive effects of statins in reducing depression and depression-like symptoms in animals [108][109][110][111][112][113][114][115] or humans [116,117], while some others stated no relationships [118][119][120]. These divergences require more detailed studies, also for elucidating the possible mechanism of the positive effects, which, in some cases, have been associated with a modulation of NMDA receptors [121] or peroxisome proliferator-activated receptor gamma (PPAR-γ) receptors, by NO inhibition [122].…”

Section: Depressionmentioning

confidence: 99%

Biocatalyzed Synthesis of Statins: A Sustainable Strategy for the Preparation of Valuable Drugs

2019

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Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are the largest selling class of drugs prescribed for the pharmacological treatment of hypercholesterolemia and dyslipidaemia. Statins also possess other therapeutic effects, called pleiotropic, because the blockade of the conversion of HMG-CoA to (R)-mevalonate produces a concomitant inhibition of the biosynthesis of numerous isoprenoid metabolites (e.g., geranylgeranyl pyrophosphate (GGPP) or farnesyl pyrophosphate (FPP)). Thus, the prenylation of several cell signalling proteins (small GTPase family members: Ras, Rac, and Rho) is hampered, so that these molecular switches, controlling multiple pathways and cell functions (maintenance of cell shape, motility, factor secretion, differentiation, and proliferation) are regulated, leading to beneficial effects in cardiovascular health, regulation of the immune system, anti-inflammatory and immunosuppressive properties, prevention and treatment of sepsis, treatment of autoimmune diseases, osteoporosis, kidney and neurological disorders, or even in cancer therapy. Thus, there is a growing interest in developing more sustainable protocols for preparation of statins, and the introduction of biocatalyzed steps into the synthetic pathways is highly advantageous-synthetic routes are conducted under mild reaction conditions, at ambient temperature, and can use water as a reaction medium in many cases. Furthermore, their high selectivity avoids the need for functional group activation and protection/deprotection steps usually required in traditional organic synthesis. Therefore, biocatalysis provides shorter processes, produces less waste, and reduces manufacturing costs and environmental impact. In this review, we will comment on the pleiotropic effects of statins and will illustrate some biotransformations nowadays implemented for statin synthesis.

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Antidepressant-like effect of simvastatin in diabetic rats

Cited by 29 publications

References 65 publications

Sex‐dependent independent prediction of incident diabetes by depressive symptoms

Sex‐dependent independent prediction of incident diabetes by depressive symptoms

Simultaneous administration of fluoxetine and simvastatin ameliorates lipid profile, improves brain level of neurotransmitters, and increases bioavailability of simvastatin

Biocatalyzed Synthesis of Statins: A Sustainable Strategy for the Preparation of Valuable Drugs

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