Antioxidant effect of sildenafil: Potential hepatoprotection via differential expression of mitochondrial proteins in apolipoprotein E knockout mice

Menezes, Thiago N.; Naumann, Gustavo B.; Mendonça, Allan B.; Leal, Marcos André Soares; Porto, Marcella L.; Teixeira-Ferreira, André; Perales, Jonás; Meyrelles, Silvana S.; Figueiredo, Suely G.; Vasquez, Elisardo C.

doi:10.1016/j.pharep.2019.01.005

Cited by 5 publications

(12 citation statements)

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“…upregulates StAR expression through stimulation of protein kinase G1 (Andric et al, 2010). Additionally, the antioxidant activity of sildenafil in rats has previously been reported (Ademosun et al, 2019;Menezes et al, 2019).…”

Section: Discussionmentioning

confidence: 93%

“…Previous studies have demonstrated that sildenafil increases testosterone hormone levels (Abdalla et al, 2012;Spitzer et al, 2013) and upregulates StAR expression through stimulation of protein kinase G1 (Andric et al, 2010). Additionally, the antioxidant activity of sildenafil in rats has previously been reported (Ademosun et al, 2019;Menezes et al, 2019).…”

Section: Discussionmentioning

confidence: 96%

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Cratoxylum formosum dyer extract alleviates testicular damage in hypertensive rats

et al. 2020

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Hypertension is a chronic disorder that contributes to cardiovascular disease (World Health, 2009). Currently, it is the major cause of morbidity and mortality in people worldwide (James et al., 2014). Hypertension associated with sexual dysfunction has been reported in male patients with hypertension (Fogari et al., 2001). Additionally, decreased sexual activity has been observed in male patients with essential hypertension, which has been associated with reduced testosterone levels (Fogari et al., 2002). A previous study has reported that serum total testosterone and epididymal sperm motility are significantly reduced in rats with nitric oxide (NO) depletion (Adedara et al., 2018). It is well known that testosterone is an essential hormone for the initiation and maintenance of spermatogenic processes (Chauhan et al., 2007), synthesised by testicular Leydig cells using cholesterol as its substrate (Li et al., 2011). The biosynthesis of testosterone requires steroidogenic acute regulatory protein (StAR), a mitochondrial cholesterol transporter, that transfers lipids from outside the mitochondrial membrane to the inside (Stocco, 2001). Reportedly,

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 96%

Cratoxylum formosum dyer extract alleviates testicular damage in hypertensive rats

et al. 2020

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“…There are evidences of antioxidative effects of sildenafil on different cell lines and animal models [ 19 , 20 , 21 , 26 , 27 , 54 , 55 , 56 ], and very recently, our group has shown that sildenafil was involved in ROS-mediated signaling through the modulation of Signal transducer and activator of transcription (STAT) 3, ERK, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-Κb), and protein kinase B (PKB/AKT), as well as in reducing the expression/secretion of proinflammatory and profibrotic cytokines in SSc fibroblasts exposed to H 2 O 2 [ 23 ]. Here, for the first time, we successfully demonstrated that the presence of sildenafil ameliorates the management of redox imbalance in SSc fibroblasts exposed to a pro-oxidant environment, reducing ROS levels and improving the efficiency of the glutathione system, as well as increasing the level of SOD and its activity.…”

Section: Discussionmentioning

confidence: 99%

“…The high potential antioxidant capability of sildenafil [ 26 , 27 ] makes this PDE5 inhibitor a good candidate for therapeutic treatment aimed to reduce oxidative damage to biological macromolecules, thus preserving cell viability.…”

Section: Introductionmentioning

confidence: 99%

The Phosphodiesterase Type 5 Inhibitor Sildenafil Improves DNA Stability and Redox Homeostasis in Systemic Sclerosis Fibroblasts Exposed to Reactive Oxygen Species

et al. 2020

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Systemic sclerosis (SSc) is a multi-system connective tissue disease characterized by the increased deposition of extracellular matrix proteins such as collagen and fibronectin. Although the pathogenesis is not completely understood, a number of studies suggest that free radicals could be the major contributors to the disease. Indeed, different studies demonstrated how oxidative stress could contribute to the fibrotic process activation at the level of the skin and visceral organs. Emerging evidences highlight the beneficial effects of sildenafil, a phosphodiesterase type 5 inhibitor (PDE5i), which protects different cell lines from the cell damage induced by reactive oxygen species (ROS). These data make sildenafil a good candidate for therapeutic treatment aimed to protect biological macromolecules against oxidative damage, thus preserving cell viability. The purpose of this study was to evaluate the sensitivity of SSc dermal fibroblasts to an oxidative insult and the ability for sildenafil to prevent/reduce the DNA damage due to ROS action. Additionally, we evaluated the capacity for sildenafil to influence redox homeostasis and cytotoxicity, as well as cell proliferation and cell cycle progression. We demonstrated that SSc fibroblasts have an increased sensitivity to a pro-oxidant environment in comparison to healthy controls. The sildenafil treatment reduced ROS-induced DNA damage, counteracted the negative effects of ROS on cell viability and proliferation, and promoted the activity of specific enzymes involved in redox homeostasis maintenance. To our knowledge, in this report, we demonstrate, for the first time, that sildenafil administration prevents ROS-induced instability in human dermal fibroblasts isolated by SSc patients. These results expand the use of PDE5i as therapeutic agents in SSc by indicating a protective role in tissue damage induced by oxidative insult.

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“…sildenafil potentiate both enzymatic and non‐enzymatic antioxidants in liver, spleen and kidney while stimulating lung inflammatory responses by the activated neutrophils, eosinophils and epithelial cells leading to production of ROS and membrane lipid peroxidation in rats 16,17 …”

Section: Introductionmentioning

confidence: 99%

Nrf2 and NF‐қB interplay in tamoxifen‐induced hepatic toxicity: A promising therapeutic approach of sildenafil and low‐dose γ radiation

Karam

Galal

Lotfy

2023

Environmental Toxicology

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Tamoxifen-induced hepatotoxicity is an inevitable side effect during breast cancer treatment. Low-dose gamma irradiation (IRR) shows many beneficial effects by stimulating various biological processes. This study evaluates the possible effect of sildenafil and low-dose gamma radiation on liver damages as new treatment strategies.Group I (control), group II: (tamoxifen), group III: (tamoxifen + Sildenafil), group IV:(tamoxifen+ irradiation) and group V: (tamoxifen +Sildenafil + irradiation). Rats were sacrificed after 5 h from tamoxifen injection. Results showed that tamoxifen caused elevation in serum AST, ALT and ALP as well hepatic ROS, iNOS, MDA, Keap-1 and NF-Kb, in addition to diminution in hepatic Nrf2 and HO-1. Exposure to low-dose gamma radiation and sildenafil amended the alterations in the measured parameters in serum and tissue. Moreover, all results were confirmed by histopathological examination. In conclusion, sildenafil and low-dose gamma radiation can mitigate the toxicity induced by tamoxifen in liver tissues. Hence, this treatment could be further evaluated as a new approach for alleviating various liver disorders.

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Antioxidant effect of sildenafil: Potential hepatoprotection via differential expression of mitochondrial proteins in apolipoprotein E knockout mice

Cited by 5 publications

References 34 publications

Cratoxylum formosum dyer extract alleviates testicular damage in hypertensive rats

Cratoxylum formosum dyer extract alleviates testicular damage in hypertensive rats

The Phosphodiesterase Type 5 Inhibitor Sildenafil Improves DNA Stability and Redox Homeostasis in Systemic Sclerosis Fibroblasts Exposed to Reactive Oxygen Species

Nrf2 and NF‐қB interplay in tamoxifen‐induced hepatic toxicity: A promising therapeutic approach of sildenafil and low‐dose γ radiation

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