scholarly journals Bladder Dysfunction in an Obese Zucker Rat: The Role of TRPA1 Channels, Oxidative Stress, and Hydrogen Sulfide

2019 ◽  
Vol 2019 ◽  
pp. 1-12
Author(s):  
Igor Blaha ◽  
María Elvira López-Oliva ◽  
María Pilar Martínez ◽  
Paz Recio ◽  
Ángel Agis-Torres ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Sulfide ◽  
Transient Receptor Potential ◽  
Bladder Dysfunction ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Antioxidant Enzyme Activities ◽  
Zucker Rat ◽  
Obese Zucker Rat ◽  
Transient Receptor

Purpose. This study investigates whether functionality and/or expression changes of transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) channels, oxidative stress, and hydrogen sulfide (H2S) are involved in the bladder dysfunction from an insulin-resistant obese Zucker rat (OZR). Materials and Methods. Detrusor smooth muscle (DSM) samples from the OZR and their respective controls, a lean Zucker rat (LZR), were processed for immunohistochemistry for studying the expression of TRPA1 and TRPV1 and the H2S synthase cystathionine beta-synthase (CBS) and cysthathionine-γ-lyase (CSE). Isometric force recordings to assess the effects of TRPA1 agonists and antagonists on DSM contractility and measurement of oxidative stress and H2S production were also performed. Results. Neuronal TRPA1 expression was increased in the OZR bladder. Electrical field stimulation- (EFS-) elicited contraction was reduced in the OZR bladder. In both LZR and OZR, TRPA1 activation failed to modify DSM basal tension but enhanced EFS contraction; this response is inhibited by the TRPA1 blockade. In the OZR bladder, reactive oxygen species, malondialdehyde, and protein carbonyl contents were increased and antioxidant enzyme activities (superoxide dismutase, catalase, GR, and GPx) were diminished. CSE expression and CSE-generated H2S production were also reduced in the OZR. Both TRPV1 and CBS expressions were not changed in the OZR. Conclusions. These results suggest that an increased expression and functionality of TRPA1, an augmented oxidative stress, and a downregulation of the CSE/H2S pathway are involved in the impairment of nerve-evoked DSM contraction from the OZR.

Hydrogen sulfide modulates IL-6/STAT3 pathway and inhibits oxidative stress, inflammation, and apoptosis in rat model of methotrexate hepatotoxicity

2019 ◽  
Vol 39 (1) ◽  
pp. 77-85 ◽  
Author(s):  
AA Fouad ◽  
HM Hafez ◽  
AAH Hamouda
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Sulfide ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Nuclear Factor Κb ◽  
Ruthenium Red ◽  
Transient Receptor Potential Vanilloid ◽  
Stat3 Pathway ◽  
Anti Inflammatory ◽  
Apoptotic Effects

Methotrexate (MTX) is a commonly used anticancer and immunosuppressive agent. However, MTX can induce hepatotoxicity due to oxidative stress, inflammation, and apoptosis. Hydrogen sulfide (H2S), the endogenous gaseous molecule, has antioxidant, anti-inflammatory, and anti-apoptotic effects. The present work explored the probable protective effect of H2S against MTX hepatotoxicity in rats and also the possible mechanisms underlying this effect. MTX was given at a single intraperitoneal (i.p.) dose of 20 mg/kg. Sodium H2S (56 µmol /kg/day, i.p.), as H2S donor, was given for 10 days, starting 6 days before MTX administration. H2S significantly reduced serum alanine aminotransferase, hepatic malondialdehyde, interleukin 6, nuclear factor κB p65, cytosolic cytochrome c, phosphorylated signal transducer and activator of transcription 3, and Bax/Bcl-2 ratio and significantly increased hepatic total antioxidant capacity and endothelial nitric oxide synthase (eNOS) in rats received MTX. In addition, H2S minimized the histopathological injury and significantly decreased the expression of STAT3 in liver tissue of MTX-challenged rats. The effects of H2S were significantly antagonized by administration of glibenclamide as KATP channel blocker, Nω-nitro-l-arginine, as eNOS inhibitor, or ruthenium red, as transient receptor potential vanilloid 1 (TRPV1) antagonist. It was concluded that H2S provided significant hepatoprotection in MTX-challenged rats through its antioxidant, anti-inflammatory, anti-apoptotic effects. These effects are most probably mediated by the ability of H2S to act as IL-6/STAT3 pathway modulator, KATP channel opener, eNOS activator, and TRPV1 agonist.

scholarly journals Hydrogen Sulfide-Evoked Intracellular Ca2+ Signals in Primary Cultures of Metastatic Colorectal Cancer Cells

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3338
Author(s):  
Pawan Faris ◽  
Federica Ferulli ◽  
Mauro Vismara ◽  
Matteo Tanzi ◽  
Sharon Negri ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Hydrogen Sulfide ◽  
Transient Receptor Potential ◽  
Primary Cultures ◽  
Receptor Potential ◽  
Cell Types ◽  
Transient Receptor Potential Vanilloid ◽  
Sodium Hydrosulfide ◽  
Reverse Mode ◽  
Transient Receptor

Exogenous administration of hydrogen sulfide (H2S) is emerging as an alternative anticancer treatment. H2S-releasing compounds have been shown to exert a strong anticancer effect by suppressing proliferation and/or inducing apoptosis in several cancer cell types, including colorectal carcinoma (CRC). The mechanism whereby exogenous H2S affects CRC cell proliferation is yet to be clearly elucidated, but it could involve an increase in intracellular Ca2+ concentration ([Ca2+]i). Herein, we sought to assess for the first time whether (and how) sodium hydrosulfide (NaHS), one of the most widely employed H2S donors, induced intracellular Ca2+ signals in primary cultures of human metastatic CRC (mCRC) cells. We provided the evidence that NaHS induced extracellular Ca2+ entry in mCRC cells by activating the Ca2+-permeable channel Transient Receptor Potential Vanilloid 1 (TRPV1) followed by the Na+-dependent recruitment of the reverse-mode of the Na+/Ca2+ (NCX) exchanger. In agreement with these observations, TRPV1 protein was expressed and capsaicin, a selective TRPV1 agonist, induced Ca2+ influx by engaging both TRPV1 and NCX in mCRC cells. Finally, NaHS reduced mCRC cell proliferation, but did not promote apoptosis or aberrant mitochondrial depolarization. These data support the notion that exogenous administration of H2S may prevent mCRC cell proliferation through an increase in [Ca2+]i, which is triggered by TRPV1.

scholarly journals The Synergistic Effect of TRPV1 on Oxidative Stress-Induced Autophagy and Apoptosis in Microglia

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Tingting Huang ◽  
Yao Lin ◽  
Qiongyi Pang ◽  
Weimin Shen ◽  
Xiang Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ischemic Stroke ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Glucose Deprivation ◽  
Transient Receptor Potential Vanilloid ◽  
Stress Injury ◽  
Stroke Treatment ◽  
Transmission Electron ◽  
Transient Receptor

Stroke mostly including ischemic stroke is the second leading mortality and disability worldwide. Oxidative stress injury occurred during ischemic stroke treatment generally. A high amount of reactive oxygen species (ROS) is involved in oxidative stress induction. Transient receptor potential vanilloid 1 (TRPV1) has been shown to regulate oxidative stress and apoptosis in microglia; however, the detailed mechanisms remain unclear. We aimed to explore whether autophagy-regulated oxidative stress and apoptosis are associated with TRPV1. The model of oxygen and glucose deprivation (OGD/R) in microglia was established. The siRNA of Atg5 and inhibitors and agonists of both autophagy and TRPV1 were involved in our study. Autophagy-related markers Atg5, LC3II/LC3I, and Beclin-1 were measured, and the autophagosome was observed under a transmission electron microscope (TEM). Caspase 3 was detected using ELISA. ROS and JC-1 were detected using flow cytometry. Apoptosis was observed by TUNEL. The results indicated that oxidative stress-induced injury and apoptosis may be impeded by the increasing autophagy, and TRPV1 inhibition could suppress the OGD/R-induced autophagy of microglia. However, the effect of TRPV1’s inhibitor on oxidative stress and apoptosis was not obvious when the autophagy was blocked. These findings suggested that TRPV1 may exhibit antioxidative and antiapoptosis effect on OGD/R-induced microglia. However, the experimental results do not fully demonstrate that the TRPV1-mediated antioxidative and antiapoptosis effect is through the affecting autophagy entirely.

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