Nebivolol, a β-blocker abrogates streptozotocin-induced behavioral, biochemical, and neurophysiological deficit by attenuating oxidative-nitrosative stress: a possible target for the prevention of diabetic neuropathy

Bhadri, Naini; Razdan, Rema; Goswami, Sumanta

doi:10.1007/s00210-017-1450-8

Cited by 7 publications

(5 citation statements)

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“…Diabetes mellitus (DM) is a complex metabolic disorder which adversely affects multiple physiological systems including the central nervous system and cardiovascular system, and the disease is associated with altered memory function, cardiac stress, endothelial dysfunction and neuropathy (Islam et al, 2017; Bhadri et al, 2018; Minaz et al, 2018). Both type 1 and type 2 diabetes induce changes in the neurones, brain and memory as seen in the case of Alzheimer’s disease (Zhao and Townsend, 2009; Ouwens et al, 2014; Rdzak and Abdelghany, 2014; King et al, 2015; Meneilly and Tessier, 2016; Morales-Corraliza et al, 2016; Chen et al, 2018; Pappas et al, 2018; Takeuchi et al, 2018; Yashkin et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Docosahexaenoic Acid Increases the Potency of Soluble Epoxide Hydrolase Inhibitor in Alleviating Streptozotocin-Induced Alzheimer’s Disease-Like Complications of Diabetes

et al. 2019

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Diabetes is a risk factor for Alzheimer’s disease and it is associated with significant memory loss. In the present study, we hypothesized that the soluble epoxide hydrolase (sEH) inhibitor N-[1-(1-oxopropyl)-4-piperidinyl]-N’-[4-(trifluoromethoxy)phenyl)-urea (also known as TPPU) could alleviate diabetes-aggravated Alzheimer’s disease-like symptoms by improving memory and cognition, and reducing the oxidative stress and inflammation associated with this condition. Also, we evaluated the effect of edaravone, an antioxidant on diabetes-induced Alzheimer’s-like complications and the additive effect of docosahexaenoic acid (DHA) on the efficacy of TPPU. Diabetes was induced in male Sprague-Dawley rats by intraperitoneally administering streptozotocin (STZ). Six weeks after induction of diabetes, animals were either treated with vehicle, edaravone (3 or 10 mg/kg), TPPU (1 mg/kg) or TPPU (1 mg/kg) + DHA (100 mg/kg) for 2 weeks. The results demonstrate that the treatments increased the memory response of diabetic rats, in comparison to untreated diabetic rats. Indeed, DHA + TPPU were more effective than TPPU alone in reducing the symptoms monitored. All drug treatments reduced oxidative stress and minimized inflammation in the brain of diabetic rats. Expression of the amyloid precursor protein (APP) was increased in the brain of diabetic rats. Treatment with edaravone (10 mg/kg), TPPU or TPPU + DHA minimized the level of APP. The activity of acetylcholinesterase (AChE) which metabolizes acetylcholine was increased in the brain of diabetic rats. All the treatments except edaravone (3 mg/kg) were effective in decreasing the activity of AChE and TPPU + DHA was more efficacious than TPPU alone. Intriguingly, the histological changes in hippocampus after treatment with TPPU + DHA showed significant protection of neurons against STZ-induced neuronal damage. Overall, we found that DHA improved the efficacy of TPPU in increasing neuronal survival and memory, decreasing oxidative stress and inflammation possibly by stabilizing anti-inflammatory and neuroprotective epoxides of DHA. In the future, further evaluating the detailed mechanisms of action of sEH inhibitor and DHA could help to develop a strategy for the management of Alzheimer’s-like complications in diabetes.

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Section: Introductionmentioning

confidence: 99%

Docosahexaenoic Acid Increases the Potency of Soluble Epoxide Hydrolase Inhibitor in Alleviating Streptozotocin-Induced Alzheimer’s Disease-Like Complications of Diabetes

et al. 2019

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“…The relaxation response to EFS in the diabetic group was enhanced in the presence of mirabegron which may be due to the neuroprotective effect of mirabegron through its NO-potentiating activity in the cavernosal nerve. Also, another study demonstrated that nebivolol was beneficial in the treatment of diabetic neuropathy [15]. A study by Oikawa et al [16] demonstrated protective effects of the β 3 -AR agonist CL316243 against N-methyl-D-aspartate-induced retinal neurotoxicity in rats by stimulation of β 3 -ARs.…”

Section: Discussionmentioning

confidence: 98%

Mirabegron, A Selective β3-Adrenoceptor Agonist Causes an Improvement in Erectile Dysfunction in Diabetic Rats

Yilmaz‐Oral

Kaya‐Sezginer

Askin

et al. 2019

Exp Clin Endocrinol Diabetes

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Aim To investigate the possible beneficial effect of mirabegron [a selective β3-adrenoceptor (AR) agonist] treatment on erectile dysfunction (ED) in streptozotocin-induced diabetic rats. Methods Sprague-Dawley rats (n=20) were divided into two groups: control group and streptozotocin-induced diabetic group. In vivo erectile responses were evaluated after intracavernosal injection of mirabegron (0.4 mg/kg) in rats. The relaxation responses to electrical field stimulation (EFS, 10 Hz), sodium nitroprusside (SNP, 10 nM) and sildenafil (1 μM) of corpus cavernosum (CC) strips were examined after the incubation with mirabegron (10 μM). β3-ARs expression and localization were determined by Western blot and immunohistochemical analyses in CC tissue. Results In vivo erectile responses of diabetic rats [intracavernasal pressure (ICP) / mean arterial pressure, 0.17±0.01] were decreased, which were restored after administration of mirabegron (0.75±0.01, P<0.001). The basal ICP (7.1±0.6 mmHg) in diabetic rats was markedly increased after mirabegron (36.1 ±5.4 mmHg, P<0.01). Mirabegron caused markedly relaxation in diabetic rat CC after phenylephrine precontraction. The relaxation responses to EFS and sildenafil were reduced in diabetic CC, which were increased in the presence of mirabegron. Mirabegron enhanced SNP-induced relaxation response in both groups. The expression and immunoreactivity of β3-ARs localized to CC smooth muscle were observed in control and diabetic rats. Conclusions This is the first study to show that intracavernosal administration of mirabegron improved erectile function and neurogenic relaxation of CC in diabetic rats. These results may be supported by further studies using combinations of mirabegron and phosphodiesterase type 5 (PDE5) inhibitors for the treatment of diabetic ED, especially in patients who do not respond to PDE5 inhibitor therapy.

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“…Streptozotocin is widely used to induce diabetes because STZ-induced experimental diabetic rats exhibit well-characterized diabetic complications and sustained hyperglycemia with a low incidence of mortality [ 12 – 14 ]. Here, STZ-induced diabetes rats were constructed to investigate the potential role of AVP and RVP in the development of DN.…”

Section: Discussionmentioning

confidence: 99%

Over-expression of arginine vasopressin in magnocellular neurosecretory cells of hypothalamus and its potential relationship with development of diabetic nephropathy

Gao

et al. 2020

aoms

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Introduction: We aimed to assess our hypothesis that the expression changes of arginine vasopressin (AVP) in the magnocellular neurosecretory cells (MNCs) of hypothalamus and V2 receptor for AVP (RVP) in kidney may contribute to the pathogenesis of diabetic nephropathy (DN). Material and methods: Twenty-five male Wistar rats were randomly assigned to the control group and the diabetes mellitus (DM) group. Periodic acid-Schiff (PAS) staining and electron microscopy were used for morphological studies. Immunohistochemical staining for glial fibrillary acidic protein (GFAP) is standard for visualization of reactive astrocytes in the hypothalamus. Hypothalamus was used for immunofluorescence of AVP. Kidney was used for immunohistochemical staining of RVP. Quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) was used for quantitative determinations of AVP mRNA in hypothalamus and RVP mRNA in kidney. Western blot was used to measure the protein expression of AVP in hypothalamus and RVP in kidney. Results: Morphological studies showed abnormalities in kidney and hypothalamus in the DM group. The number of neurons and the gray value of astrocytes in hypothalamus in the DM group were markedly decreased. The expression level of AVP in hypothalamus and the expression level of RVP in kidney of DM rats were significantly increased. The positive correlations between the proteinuria and expression (mRNA and protein) of AVP, proteinuria and expression (mRNA and protein) of RVP, and the expression of AVP and RVP levels were found. Conclusions: AVP was upregulated in the MNCs of hypothalamus and RVP was upregulated in kidney in streptozotocin-induced DM rats, indicating their potential roles in the development of DN.

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Nebivolol, a β-blocker abrogates streptozotocin-induced behavioral, biochemical, and neurophysiological deficit by attenuating oxidative-nitrosative stress: a possible target for the prevention of diabetic neuropathy

Cited by 7 publications

References 62 publications

Docosahexaenoic Acid Increases the Potency of Soluble Epoxide Hydrolase Inhibitor in Alleviating Streptozotocin-Induced Alzheimer’s Disease-Like Complications of Diabetes

Docosahexaenoic Acid Increases the Potency of Soluble Epoxide Hydrolase Inhibitor in Alleviating Streptozotocin-Induced Alzheimer’s Disease-Like Complications of Diabetes

Mirabegron, A Selective β3-Adrenoceptor Agonist Causes an Improvement in Erectile Dysfunction in Diabetic Rats

Over-expression of arginine vasopressin in magnocellular neurosecretory cells of hypothalamus and its potential relationship with development of diabetic nephropathy

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