PnPP-19 Peptide Restores Erectile Function in Hypertensive and Diabetic Animals Through Intravenous and Topical Administration
The Journal of Sexual Medicine, ISSN: 1743-6095, Vol: 16, Issue: 3, Page: 365-374
2019
- 8Citations
- 42Captures
- 11Mentions
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Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
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Metrics Details
- Citations8
- Citation Indexes7
- CrossRef7
- Patent Family Citations1
- 1
- Captures42
- Readers42
- 42
- Mentions11
- News Mentions11
- 11
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Article Description
With the aim of overcoming the high toxicity of PnTx2-6 (or δ-CNTX-Pn2a), a toxin from the venom of the armed spider ( Phoneutria nigriventer ), the 19-aminoacid peptide, PnPP-19 ( P nigriventer potentiator peptide), was synthesized based on molecular modeling studies of PnTx2-6. PnPP-19 improved the erectile function of normotensive rats and mice, without eliciting side effects, and no signs of toxicity were observed. In addition, PnPP-19 was able to potentiate the effect of sildenafil. To evaluate the efficacy of PnPP-19 in hypertensive and diabetic mouse/rat models in restoring erectile function, after topical administration; verify the biodistribution of PnPP-19 administration (topical and intravenous), permeation, and cyclic guanosine monophosphate (cGMP)/nitric oxide via implication. Corpus cavernosum relaxation was evaluated using cavernous strips from male spontaneous hypertensive rats (SHR) and from streptozotocin (STZ)-diabetic mice contracted with phenylephrine and submitted to electrical field stimulation before and after incubation with PnPP-19 (10 −8 mol/L, 10 minutes) or vehicle. This procedure was also used to determine cGMP/nitric oxide levels, at 8 Hz and to check the effect of PnPP-19 with sildenafil citrate. Biodistribution assays were performed using iodine 123–radiolabeled PnPP-19. In vivo erectile function was evaluated using intracavernosal pressure/main arterial pressure ratio in STZ-diabetic rats after PnPP-19 topical administration. PnPP-19 may become a new drug able to fill the gap in the pharmacologic treatment of erectile dysfunction, especially for hypertensive and diabetic individuals PnPP-19 potentiated corpus cavernosum relaxation, in both control and SHR rats. SHR-cavernosal tissue treated with PnPP-19 (1–32 Hz) reached the same relaxation levels as control Wistar rats (16 and 32 Hz). PnPP-19 treatment improved cavernosal tissue relaxation in STZ-diabetic mice and rats. PnPP-19 enhanced cGMP levels in STZ-diabetic mice corpus cavernosum strips. After topical or intravenous administration in rats, 123 I-PnPP-19 was mainly recruited to the penis. When topically administered (400 μg/rat), PnPP-19 restores erectile function in STZ-diabetic rats, also improving it in healthy rats by increasing the intracavernosal pressure/main arterial pressure ratio. PnPP-19 exhibited an additive effect when co-administered with sildenafil, showing a novel mode of action regardless of phosphodiesterase type 5 inhibition. PnPP-19 seems to be an indicated drug to be tested to treat ED in diabetic and hypertensive patients. PnPP-19, although active by topical application and showing safety to human beings (not shown), has low permeability, about 10% of the applied dose. Our results showed that PnPP-19 may emerge as a potent new drug that can be topically administered, becoming a promising alternative for erectile dysfunction treatment. Nunes da Silva C, Pedrosa Nunes K, De Marco Almeida F, et al. PnPP-19 Peptide Restores Erectile Function In Hypertensive And Diabetic Animals Through Intravenous And Topical Administration. J Sex Med 2019;16:365–374.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S1743609519300050; http://dx.doi.org/10.1016/j.jsxm.2019.01.004; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85061451934&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/30773502; https://academic.oup.com/jsm/article/16/3/365/6980734; https://dx.doi.org/10.1016/j.jsxm.2019.01.004; https://academic.oup.com/jsm/article-abstract/16/3/365/6980734?redirectedFrom=fulltext; https://www.jsm.jsexmed.org/article/S1743-6095(19)30005-0/abstract; https://academic.oup.com/jsm/jsm; https://www.jsm.jsexmed.org/article/S1743-6095(19)30005-0/fulltext
Oxford University Press (OUP)
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