Modulation of oxidative stress, apoptosis, and calcium entry in leukocytes of patients with multiple sclerosis by Hypericum perforatum.
OBJECTIVE
Hypericum perfortarum (HP, St John's wort) is a modulator of Ca(2+) entry in neutrophils and it may modulate intracellular free Ca(2+) ([Ca(2+)]i) entry in leukocytes of patients with multiple sclerosis (MS). We investigated effects of HP on oxidative stress, apoptosis, and [Ca(2+)]i concentrations in serum and leukocytes of patients with MS.


METHODS
Neutrophils of nine newly diagnosed MS patients and nine healthy subjects within four subgroups were used in the study. The first group was a control; the second group was patients with MS. The neutrophils from patient group were incubated non-specific TRPM2 channel blocker (2-APB), voltage-gated calcium channel blockers, verapamil and diltiazem (V + D) with HP before N-formyl-L-methionyl-L-leucyl-L-phenylalanine stimulation, respectively.


RESULTS
Neutrophil and serum lipid peroxidation, neutrophil apoptosis and [Ca(2+)]i levels in patients with MS were higher than in control although their levels were decreased by HP, 2-APB, and V + D incubations. The modulator role of V + D in MS and MS + HP groups was higher than in the 2-APB group. Neutrophilic glutathione peroxidase (GSH-Px) and serum vitamin A and E concentrations were lower in the MS group than in control. However, the neutrophil GSH-Px activity was increased by HP incubation. The neutrophil reduced glutathione, serum vitamin C and β-carotene concentrations did not change in control and patients.


CONCLUSIONS
We observed that HP-induced protective effects on oxidative stress and [Ca(2+)]i concentrations by modulating transient receptor potential and voltage gated calcium channel in the patients with MS. Thus, it may provide useful treatment of neutrophil activity in the patients.
Mustafa
M
Naziroglu
Suleyman
S
Kutluhan
Ishak Suat
IS
Ovey
Mehmet
M
Aykur
Vedat Ali
VA
Yurekli
D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D001205:Ascorbic Acid / Q000097:blood; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D016022:Case-Control Studies; D002478:Cells, Cultured; D004110:Diltiazem / Q000494:pharmacology; D005260:Female; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D020902:Hypericum / Q000737:chemistry*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology; D014801:Vitamin A / Q000097:blood; D014810:Vitamin E / Q000097:blood; D055815:Young Adult; D019207:beta Carotene / Q000097:blood
D002121:Calcium Channel Blockers; D010936:Plant Extracts; D019207:beta Carotene; D014801:Vitamin A; D014810:Vitamin E; D014700:Verapamil; D005979:Glutathione Peroxidase; D004110:Diltiazem; D005978:Glutathione; D001205:Ascorbic Acid; D002118:Calcium
Inflammation; Intracellular Ca2+ concentration; Multiple sclerosis; Neutrophils; Oxidative stress; TRP Channels