Promethazine inhibits neuronal apoptosis via PI3K/Akt signaling pathway in rats with cerebral infarction
Authors: S-F Ding
X-D Pan
X-L Chen
L Li
D Kou
H-L Hu
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: promethazine; neuronal apoptosis; cerebral infarction; PI3K/Akt signaling pathway; Sprague-Dawley rats
Affiliations: Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, China. .

Abstract:  Objective: To study the effect of promethazine on neuronal apoptosis in rats with cerebral infarction (CI) through the phosphatidylinositol 3-hydroxy kinase/protein kinase B (PI3K/Akt) signaling pathway. Materials and methods: A total of 36 Sprague-Dawley rats were randomly divided into the sham group (n=12), model group (n=12), and promethazine group (n=12). The external carotid artery was only exposed in the model group, and the ischemia-reperfusion model after CI was established using the suture method in the other two groups. After modeling, the normal saline was intraperitoneally injected in the sham group and model group, while promethazine was intraperitoneally injected in the promethazine group. The rats were sampled after 1 week of intervention. The neurological deficits of rats were evaluated using the Zea-Longa score, and the cognitive function, the spatial learning, and memory of rats were detected via the water maze test. Moreover, the expressions of B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in brain tissues were detected via immunohistochemistry, and the relative protein expressions of PI3K p85, PI3K p110, and p-Akt were detected via Western blotting. The mRNA expressions of Bax and Bcl-2 were detected via quantitative Polymerase Chain Reaction (qPCR), and the apoptosis was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Results: The Zea-Longa score was significantly increased in the model group and promethazine group compared with that in the sham group (p&lt;0.05), while it significantly declined in the promethazine group compared with that in the model group (p&lt;0.05). The escape latency was significantly prolonged and the times of crossing platform were significantly reduced in the model group and promethazine group compared with those in the sham group (p&lt;0.05), while the escape latency was significantly shortened and the times of crossing platform were significantly increased in the promethazine group compared with those in the model group (p&lt;0.05). Compared with those in the sham group, the positive expression of Bax was significantly increased, while the positive expression of Bcl-2 was remarkably decreased in the model group and promethazine group (p&lt;0.05). Compared with those in the model group, the positive expression of Bax was significantly decreased, while the positive expression of Bcl-2 was remarkably increased in the promethazine group (p&lt;0.05). Besides, the model group and promethazine group had evidently higher relative protein expressions of PI3K p85, PI3K p110, and p-Akt than the sham group (p&lt;0.05), while the promethazine group also had evidently higher relative protein expressions of PI3K p85, PI3K p110, and p-Akt than the model group (p&lt;0.05). Compared with the sham group, model group, and promethazine group had remarkably increased relative mRNA expression of Bax, and remarkably decreased relative mRNA expression of Bcl-2 (p&lt;0.05). Compared with those in the model group, the relative mRNA expression of Bax was remarkably decreased, while the relative mRNA expression of Bcl-2 was remarkably increased in the promethazine group (p&lt;0.05). Finally, the apoptosis rate was significantly higher in the model group and promethazine group than that in the sham group (p&lt;0.05), while it was significantly lower in the promethazine group than that in the model group (p&lt;0.05). Conclusions: Promethazine inhibits neuronal apoptosis in CI rats by upregulating the PI3K/Akt signaling pathway, thereby exerting a protective effect. 

Retracted: Yes

PubPeer comments:
 Fig 3:  Immunohistochemical detection . ![file] One panel also appears (labeled as Bcl-2 rather than Bax) in work by other authors. Figure 2 from [Pan et al (2019)] :  Immunohistochemical detection of Bax and Bcl-2 expressions . ![file] , 
 Left: Figure 5.  Protein expressions detected via Western blotting (stretched horizontally to 135% for convenience). Upper right, rotated through 180 deg. Lower right: Fig 4 from [Lou et al (2019)] . ![file] Many unexpected similarities! No authors in common. , 
 #2 At left: Figure 5.  Protein expressions detected via Western blotting (stretched horizontally to 135% for convenience). At right: Figure 3 from [Long et al (2019)] .  Protein expression detected via Western blotting . ![file] UPDATE #2 Clockwise from upper left: Figure 3 from [Sun et al (2019)] .  NF-u03baB protein expression determined through Western blotting ; Fig 3 from [Long et a (2019)] ; Fig 4 from [Lou et al (2019)] ; and Figure 5 from [Pan et al (2019)] . ![file] That is a versatile loading control. , 
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 Withdrawn [January 2021] . *The article u201cPromethazine inhibits neuronal apoptosis via PI3K Akt signaling pathway in rats with cerebral infarction, by X.-D. Pan, X.-L. Chen, S.-F. Ding, D. Kou, H.-L. Hu, L. Li, published in Eur Rev Med Pharmacol Sci 2019; 23 (3 Suppl): 126-134u2013DOI: 10.26355 eurrev_201908_18639u2013PMID: 31389591u201d has been withdrawn from the authors stating that they u201chave not yet studied their work completely and have some difficulties answering questions and quickly providing solutions in the paperu201d.* *The Publisher apologizes for any inconvenience this may cause.* ,