The protective effect of vinpocetine against Estradiol-benzoate induced cervical hyperkeratosis in female rats via modulation of SIRT1/Nrf2, and NLRP3 inflammasome – PubMed Black Hawk Supplements

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The current study was assigned to determine the putative preventive role of vinpocetine (VIN) in cervical hyperkeratosis (CHK) in female rats. Estradiol Benzoate (EB) was utilized in a dose f (60 μg/100 g, i.m) three times/week for 4 weeks to induce cervical hyperkeratosis. VIN was administered alone in a dose of (10 mg/kg/day, orally) for 4 weeks and in the presence of EB. Levels of malondialdehyde (MDA), total nitrites (NOx), reduced glutathione (GSH), interleukin-18 (IL-18), IL-1β, tumor…
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The protective effect of vinpocetine against Estradiol-benzoate induced cervical hyperkeratosis in female rats via modulation of SIRT1/Nrf2, and NLRP3 inflammasome - PubMed

The protective effect of vinpocetine against Estradiol-benzoate induced cervical hyperkeratosis in female rats via modulation of SIRT1/Nrf2, and NLRP3 inflammasome

Remon R Rofaeil et al. Sci Rep. .

Abstract

The current study was assigned to determine the putative preventive role of vinpocetine (VIN) in cervical hyperkeratosis (CHK) in female rats. Estradiol Benzoate (EB) was utilized in a dose f (60 μg/100 g, i.m) three times/week for 4 weeks to induce cervical hyperkeratosis. VIN was administered alone in a dose of (10 mg/kg/day, orally) for 4 weeks and in the presence of EB. Levels of malondialdehyde (MDA), total nitrites (NOx), reduced glutathione (GSH), interleukin-18 (IL-18), IL-1β, tumor necrosis factor-alpha (TNF-α) were measured in cervical tissue. The expression of NLRP3/GSDMD/Caspase-1, and SIRT1/Nrf2 was determined using ELISA. Cervical histopathological examination was also done. EB significantly raised MDA, NOx, TNF-α, IL-18, IL-1β, and GSDMD and up-regulated NLRP3/Caspase-1 proteins. However, GSH, SIRT1, and Nrf2 levels were reduced in cervical tissue. VIN significantly alleviates all biochemical and histopathological abnormalities. VIN considerably mitigates EB-induced cervical hyperkeratosis via NLRP3-induced pyroptosis and SIRT1/Nrf2 signaling pathway.

Keywords: Estradiol; Hyperkeratosis; NLRP3; Nrf2; Vinpocetine.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1

Cervical tissue levels of TNF-α (A), IL1β (B), and IL18 (C). Data are represented as mean ± SEM (n = 6). Where ###p < 0.001, relative to control group, **p < 0.01 relative to EB group and ***p < 0.001 relative to EB group. VIN; Vinpocetine, EB; Estradiol-benzoate, TNF-α; Tumor necrosis factor-alpha, IL18; Interleukin 18, and IL1β; Interleukin 1β.

Figure 2
Figure 2

Cervical tissue levels of SIRT1 (A), and Nrf2 (B). Data are represented as mean ± SEM (n = 6). Where ###p < 0.001, relative to control group, and ***p < 0.001 relative to EB group. VIN; vinpocetine, EB; Estradiol-benzoate, SIRT1; Silent mating type information regulation 2 homolog 1, and Nrf2; Nuclear factor erythroid 2-related factor 2.

Figure 3
Figure 3

Cervical tissue levels of NLRP3 (A), GSDMD (B), and Caspase 1 (C). Data are represented as mean ± SEM (n = 6). Where ###p < 0.001, relative to control group, and ***p < 0.001 relative to EB group. VIN; vinpocetine, EB; Estradiol-benzoate, and NLRP3 = NOD-like receptor family pyrin domain containing 3.

Figure 4
Figure 4

Impact of VIN on histopathological picture of rats’ cervices. Control group, and VIN group (A,B) displaying normal cervices lined by stratified squamous non keratinized epithelium. EB group (C) showing diffuse and marked cervical hyperkeratosis. EB + VIN group (D) displaying only mild and focal areas of hyperkeratosis, (×200). EB; Estradiol-benzoate, VIN; Vinpocetine.

Figure 5
Figure 5

Graph outlining the mechanism of EB-induced CHK and the potential protective effect of VIN. One of the authors, Ehab E. Sharata, used Microsoft PowerPoint to create this graph.

References

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The protective effect of vinpocetine against Estradiol-benzoate induced cervical hyperkeratosis in female rats via modulation of SIRT1/Nrf2, and NLRP3 inflammasome – PubMed