N-acetyl cysteine reduces oxidative toxicity, apoptosis, and calcium entry through TRPV1 channels in the neutrophils of patients with polycystic ovary syndrome

Abstract

Polycystic ovary syndrome (PCOS) is a common inflammatory and oxidant disease with an uncertain pathogenesis. N-acetyl cysteine (NAC) decreases oxidative stress, intracellular free calcium ion [Ca(2+)]i, and apoptosis levels in human neutrophil. We aimed to investigate the effects of NAC on apoptosis, oxidative stress, and Ca(2+) entry through transient receptor potential vanilloid 1 (TRPV1) and TRP melastatin 2 (TRPM2) channels in neutrophils from patients with PCOS. Neutrophils isolated from PCOS group were investigated in three settings: (1) after incubation with TRPV1 channel blocker capsazepine or TRPM2 channel blocker 2-aminoethyl diphenylborinate (2-APB), (2) after supplementation with NAC (for 6 weeks), and (3) with combination (capsazepine + 2-APB + NAC) exposure. The neutrophils in TRPM2 and TRPV1 experiments were stimulated by N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP; 1 μM) and capsaicin (10 μM) as concentration agonists, respectively. Neutrophil lipid peroxidation and capsaicin-induced increase in [Ca(2+)]i concentrations were reduced by capsazepine and NAC treatments. However, the [Ca(2+)]i concentration did not change by fMLP stimulation. Neutrophil lipid peroxidation, apoptosis, caspase-3, caspase-9, cytosolic reactive oxygen species production, and mitochondrial membrane depolarization values were decreased by NAC treatment although neutrophil glutathione peroxidase and reduced glutathione levels were increased by the NAC treatment. Serum lipid peroxidation, luteinizing hormone, testosterone, insulin, interleukin-1 beta, and homocysteine levels were decreased by NAC treatment although serum vitamin A, beta-carotene, vitamin E, and total antioxidant status were increased by the NAC treatment. In conclusion, NAC reduced oxidative stress, apoptosis, cytokine levels, and Ca(2+) entry through TRPV1 channel, which provide supportive evidence that oxidative stress and TRPV1 channel plays a key role in etiology of PCOS.

Modulation of Human Neutrophil Responses by the Essential Oils from Ferula akitschkensis and Their Constituents

“…Evaluation of these compounds in neutrophils showed that the mixed TRPA1/TRPV3/TRPM8 agonists thymol and menthol activated [Ca 2+ ] i flux with EC 50 values in the mid-micromolar range, whereas the other tested monoterpenes were inactive. Furthermore, the TRPV1 agonist capsaicin also stimulated [Ca 2+ ] i flux in human neutrophils (Table 4), which is consistent with previous studies 25 . Together, these results suggest a role of TRP channels in neutrophil responses to essential oil-derived monoterpenes, such as those found in essential oils from Ferula and other plant species.…”

Antioxidant treatment ameliorates experimental diabetes‐induced depressive‐like behaviour and reduces oxidative stress in brain and pancreas

“…In this context, agents that attenuate oxidative stress or associated factors, such as inflammation and energy metabolism impairment, could be important therapeutic targets for both diabetes and MDD. Antioxidant drugs, such as N ‐acetyl‐ l ‐cysteine (NAC) and deferoxamine (DFX), have shown anti‐inflammatory and antioxidant properties by reducing cytokines and oxidative stress, respectively (De Flora et al , 1991; ). Moreover, both NAC and DFX exerted beneficial effects on both diabetes and depression .…”

Icaritin protects against oxidative stress-induced injury in cardiac H9c2 cells via Akt/Nrf2/HO-1 and calcium signalling pathways

“…A number of studies have shown that t-BHP treatment increases Ca 2+ release from Ca 2+ stores in endoplasmic and sarcoplasmic reticulum, causing oxidative cell death by targeting mitochondrial permeability and polarization of ΔΨm (Byrne, Lemasters, & Nieminen, 1999;Piret et al, 2004;Zima & Blatter, 2006). Restoration of ΔΨm is crucial for mitochondrial integrity and free radical regulation (Kose & Naziroglu, 2015;Yuruker, Naziroglu, & Senol, 2015). Our results indicated that icaritin was associated with a concentrationdependent maintenance of ΔΨm in t-BHP treated H9c2 cells.…”