Pentoxifylline Alleviates Perinatal Hypoxic-Ischemia-Induced Short-term Memory Impairment by Suppressing Apoptosis in the Hippocampus of Rat Pups

Park, Je Hoon; Kim, Sung Eun; Jin, Jiaqi; Choi, Han Sung; Kim, Sang Hoon; Ko, Il‐Gyu

doi:10.5213/inj.1632532.266

Cited by 12 publications

(17 citation statements)

References 32 publications

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“…Hypoxic-ischemic brain damage deteriorated short-term memory in rats (Park et al, 2016) and ischemia impaired short-term memory in gerbils (Choi et al, 2017). Treadmill exercise improved memory function through suppressing apoptosis in the hippocampus following cerebral ischemia (Choi et al, 2017;Park et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…Apoptosis after cerebral ischemia is the final event that leads to the process of cell death (Mattson et al, 2001). Ischemia triggers apoptotic neurodegeneration through caspase-3 activation (Choi et al, 2017;Park et al, 2016). In the ischemic attack, increased expression of Bcl-2 inhibited apoptosis, while over-expression of Bax promoted apoptosis (Choi et al, 2017;Park et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…Ischemia triggers apoptotic neurodegeneration through caspase-3 activation (Choi et al, 2017;Park et al, 2016). In the ischemic attack, increased expression of Bcl-2 inhibited apoptosis, while over-expression of Bax promoted apoptosis (Choi et al, 2017;Park et al, 2016). Increase of Bax to Bcl-2 ratio represents apoptotic cell death (Song et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Apoptosis after cerebral ischemia is one of the major pathways that lead to the process of cell death (Mattson et al, 2001). Two important groups of proteins involved in ischemic apoptotic cell death are the members of the Bcl-2 family and a class of cysteine proteases known as caspases (Choi et al, 2017;Park et al, 2016). Bcl-2 family is classified into two functionally distinct groups: Bcl-2, an anti-apoptotic protein, and Bax, a pro-apoptotic protein.…”

Section: Introductionmentioning

confidence: 99%

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Treadmill exercise ameliorates memory impairment through ERK-Akt-CREB-BDNF signaling pathway in cerebral ischemia gerbils

et al. 2020

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Neuronal cell death in the hippocampus by cerebral ischemia causes disability of memory function. Cerebral ischemia also alters the expressions of brain-derived neurotrophic factor (BDNF), cyclic adenosine monophosphate-responsive element binding protein (CREB), extracellular signal-regulated protein kinase (ERK), and phosphatidylinositol 3-kinase/protein kinase B (Akt). In the present study, we investigated the effect of treadmill exercise on cerebral ischemia in relation with ERK-Akt-CREB-BDNF signaling pathway in the hippocampus using gerbils. Induction of cerebral ischemia deteriorated short-term memory with suppression of phosphorylation of ERK-Akt-CREB-BDNF pathway in the hippocampus of gerbils. Enhancement of apoptosis in the hippo-campus was accompanied in the ischemia gerbils. Treadmill exercise improved short-term memory through enhancing phosphorylation of ERK-Akt-CREB-BDNF pathway with suppressing apoptosis in the hippocampus of the ischemia gerbils. The present results suggest that improvement of memory function after cerebral ischemia by treadmill exercise may be involved in the ERK-Akt-CREB-BDNF signaling pathway, resulting in inhibition of apoptosis in the hippocampus.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Treadmill exercise ameliorates memory impairment through ERK-Akt-CREB-BDNF signaling pathway in cerebral ischemia gerbils

et al. 2020

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“…cAMP has been frequently measured in in vitro studies, including those on pharmacodynamics of PDE inhibitors (D’Alessandro et al 2013 ; Huang et al 2015 ; Massimi et al 2017 ). Moreover, there are several examples of measuring its concentrations in animal tissues (Kitazawa et al 1999 ; Jin et al 2004 ; Park et al 2016 ) or plasma (Cheng et al 1997 ; Tanahashi et al 1999 ). However, the pharmacodynamic data obtained in these studies have not been analysed quantitatively.…”

Section: Discussionmentioning

confidence: 99%

PK/PD studies on non-selective PDE inhibitors in rats using cAMP as a marker of pharmacological response

Świerczek

Wyska

Baś

et al. 2017

Naunyn-Schmiedeberg's Arch Pharmacol

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In recent years, phosphodiesterase (PDE) inhibitors have been frequently tested for the treatment of experimental inflammatory and immune disorders. It is suggested that anti-inflammatory properties of PDE inhibitors are related to their ability to increase cAMP levels. The aim of this study was to verify the hypothesis that cAMP may be a useful marker of pharmacological response following administration of non-selective PDE inhibitors (pentoxifylline and (±)-lisofylline) to endotoxemic rats. Male Wistar rats were administered LPS (1 mg kg−1, i.v.) simultaneously with either compound given at two doses (40 and 80 mg kg−1, i.v.). Levels of cAMP and both compounds in animal plasma were measured by the validated HPLC methods. Pharmacokinetic-pharmacodynamic analysis was performed using basic and modified indirect response (IDR) models II in Phoenix WinNonlin. The results of this study indicate that, in contrast to pentoxifylline, (±)-lisofylline demonstrates a non-linear pharmacokinetics in rats with endotoxemia. In vitro study using human recombinant PDE4B and PDE7A revealed the occurrence of additive interaction between studied compounds. Moreover, (±)-lisofylline is a more potent inhibitor of PDEs compared to pentoxifylline, as evidenced by lower IC50 values. Following administration of both compounds, levels of cAMP in rat plasma increased in a dose-dependent manner. The modified IDR model II better described cAMP levels over time profiles. The validity of the proposed marker was confirmed by measuring plasma TNF-α levels in the studied animals. In conclusion, cAMP may be used in future preclinical and clinical studies of some PDE inhibitors to evaluate the drug concentration–effect relationship.

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Rolipram and pentoxifylline combination ameliorates the morphological abnormalities of dorsal root ganglion neurons in experimental diabetic neuropathy by reducing mitochondrial dysfunction and apoptosis

Dastgheib

Falak

Moghaddam

et al. 2023

J Biochem & Molecular Tox

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Diabetic neuropathy (DN) is the most prevalent complication of diabetes. Pharmacological treatments for DN are often limited in efficacy, so the development of new agents to alleviate DN is essential. The aim of this study was to evaluate the effects of rolipram, a selective phosphodiesterase‐4 inhibitor (PDE‐4I), and pentoxifylline, a general PDE inhibitor, using a rat model of DN. In this study, a diabetic rat model was established by i.p. injection of STZ (55 mg/kg). Rats were treated with rolipram (1 mg/kg), pentoxifylline (100 mg/kg), and combination of rolipram (0.5 mg/kg) and pentoxifylline (50 mg/kg), orally for 5 weeks. After treatments, sensory function was assessed by hot plate test. Then rats were anesthetized and dorsal root ganglion (DRG) neurons isolated. Cyclic adenosine monophosphate (cAMP), adenosine triphosphate (ATP, adenosine diphosphate and mitochondrial membrane potential (MMP) levels, Cytochrome c release, Bax, Bcl‐2, caspase‐3 proteins expression in DRG neurons were assessed by biochemical and ELISA methods, and western blot analysis. DRG neurons were histologically examined using hematoxylin and eosin (H&E) staining method. Rolipram and/or pentoxifylline significantly attenuated sensory dysfunction by modulating nociceptive threshold. Rolipram and/or pentoxifylline treatment dramatically increased the cAMP level, prevented mitochondrial dysfunction, apoptosis and degeneration of DRG neurons, which appears to be mediated by inducing ATP and MMP, improving cytochrome c release, as well as regulating the expression of Bax, Bcl‐2, and caspase‐3 proteins, and improving morphological abnormalities of DRG neurons. We found maximum effectiveness with rolipram and pentoxifylline combination on mentioned factors. These findings encourage the use of rolipram and pentoxifylline combination as a novel experimental evidence for further clinical investigations in the treatment of DN.

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Pentoxifylline Alleviates Perinatal Hypoxic-Ischemia-Induced Short-term Memory Impairment by Suppressing Apoptosis in the Hippocampus of Rat Pups

Cited by 12 publications

References 32 publications

Treadmill exercise ameliorates memory impairment through ERK-Akt-CREB-BDNF signaling pathway in cerebral ischemia gerbils

Treadmill exercise ameliorates memory impairment through ERK-Akt-CREB-BDNF signaling pathway in cerebral ischemia gerbils

PK/PD studies on non-selective PDE inhibitors in rats using cAMP as a marker of pharmacological response

Rolipram and pentoxifylline combination ameliorates the morphological abnormalities of dorsal root ganglion neurons in experimental diabetic neuropathy by reducing mitochondrial dysfunction and apoptosis

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