title: 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.
authors: Department of Obstetrics and Gynecology, Faculty of Medicine, Suleyman Demirel University , Isparta , Turkey.
authors: S A
authors: SA
authors: Köse
authors: M
authors: M
authors: Nazıroğlu
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000328:Adult; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D016207:Cytokines / Q000187:drug effects; D005260:Female; D006801:Humans; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*; D050053:TRPM Cation Channels / Q000378:metabolism; D050916:TRPV Cation Channels / Q000187:drug effects / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000975:Antioxidants; D016207:Cytokines; D050053:TRPM Cation Channels; C121934:TRPM2 protein, human; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D002118:Calcium; D000111:Acetylcysteine
keywords: N-acetyl cysteine; TRPV1 channel; neutrophil; antioxidant; inflammation; polycystic ovary syndrome