Cell lines

Bovine aortic endothelial cells

Preparation Method

Bovine aortic endothelial cells (BAECs), with or without pretreatment of sildenafil (5 μM at 5 minutes before radiation), were used to test endothelial dysfunction in response to external beam radiation at 10e15 Gy. Generation of reactive oxygen species (ROS) was studied.

Reaction Conditions

5 μM at 5 minutes before radiation

Applications

sildenafil (5 μM) added 5 minutes before 10 Gy radiation inhibited SDRT-induced apoptosis at 8 hours by 45% from 17.4% (SDRT alone) to 9.6% (SDRTth sildenafil 5 μM).

Animal models

Male, aged (16-18 months) Wistar rats

Preparation Method

Male, aged (16-18 months) Wistar rats were subjected to MMI (800 ± 100, 70-100 μm cholesterol crystals injected into the internal carotid artery) and treated with or without Sildenafil (2 mg/kg, i.p) starting at 24 h after MMI daily for 28 days.

Dosage form

2 mg/kg, i.p

Applications

Sildenafil treatment in aged MMI rats significantly improves short term memory evaluated by the novel object recognition test and improves spatial learning and memory in the Morris water maze test compared to aged control MMI rats.

Sildenafil, as a phosphodiesterase-5 (PDE-5) inhibitors, used for treatment of pulmonary arterial hypertension (PAH).^[1]Sildenafil can also treat erectile dysfunction caused by the psychological stress of infertility treatments.^[3]

In vitro, the IC50 of sildenafil for PDE5 was 5.22 nM.^[4]In vitro experiment it indicated that treatment with 1 μmol/L sildenafil in pulmonary artery smooth muscle cells potentiated the phosphorylation of ERK1/ERK2, an increase in the percentage of cells in S phase and cell proliferation, compared with serotonin stimulation alone.^[5]In vitro, the combination of sildenafil with cisplatin can improve cell toxicity and anticancer effect of cisplatin.^[7]

In vivo efficacy test it shown that sildenafil dose-dependently (1 mg/kg every 12 hours for 14 days, p.o.) reduced basal tone and increased electrically-induced relaxation of dog lower oesophageal sphincter samples.^[2]In vivo, treatment 10 mg/kg sildenafil after 72 h significantly increased the number of COX-2+ microglia/macrophages in the penumbra, but was remarkably decreased 8 days after ischemia.^[6]SILD - EAE mice were treated with 25mg/kg Sildenafil (s.c.), the results shown that sildenafil inhibited nitrosative stress and augmented the levels of LC3, beclin-1, ATG5, p-CREB and BDNF and decreased mTOR levels, as well as augmented p-AMPK.^[8]In vivo study it demonstrated that treatment with 40 mg/kg/day sildenafil can improve radiation-induced oral mucositis and decrease the apoptosis of mucosal cells via attenuation of inflammation and oxidative stress.^[9]

References:
[1]Bhogal S, et al. Sildenafil for Pulmonary Arterial Hypertension. Am J Ther. 2019 Jul/Aug;26(4):e520-e526.
[2]Quintavalla F, et al. Sildenafil improves clinical signs and radiographic features in dogs with congenital idiopathic megaoesophagus: a randomised controlled trial. Vet Rec. 2017 Apr 22;180(16):404.
[3]Scherzer ND, et al. Sildenafil's impact on male infertility: what has changed in 20 years? Int J Impot Res. 2019 Mar;31(2):71-73.
[4]Wang Z, et al. The selectivity and potency of the new PDE5 inhibitor TPN729MA. J Sex Med. 2013 Nov;10(11):2790-7.
[5]Li BB, et al. Sildenafil potentiates the proliferative effect of porcine pulmonary artery smooth muscle cells induced by serotonin in vitro. Chin Med J (Engl). 2011 Sep;124(17):2733-40.
[6]Moretti R, et al. Sildenafil, a cyclic GMP phosphodiesterase inhibitor, induces microglial modulation after focal ischemia in the neonatal mouse brain. J Neuroinflammation. 2016 Apr 28;13(1):95.
[7]Hassanvand F, et al. Sildenafil enhances cisplatin-induced apoptosis in human breast adenocarcinoma cells. J Cancer Res Ther. 2020 Oct-Dec;16(6):1412-1418.
[8]Duarte-Silva E, et al. Sildenafil Alleviates Murine Experimental Autoimmune Encephalomyelitis by Triggering Autophagy in the Spinal Cord. Front Immunol. 2021 May 13;12:671511.
[9]Ala M, et al. Sildenafil improves radiation-induced oral mucositis by attenuating oxidative stress, NF-κB, ERK and JNK signalling pathways. J Cell Mol Med. 2022 Aug;26(16):4556-4565.