title: Curcumin and folic acid abrogated methotrexate induced vascular endothelial dysfunction.
abstract: Methotrexate, an antifolate drug widely used in rheumatoid arthritis, psoriasis, and cancer, is known to cause vascular endothelial dysfunction by causing hyperhomocysteinemia, direct injury to endothelium or by increasing the oxidative stress (raising levels of 7,8-dihydrobiopterin). Curcumin is a naturally occurring polyphenol with strong antioxidant and anti-inflammatory action and therapeutic spectra similar to that of methotrexate. This study was performed to evaluate the effects of curcumin on methotrexate induced vascular endothelial dysfunction and also compare its effect with that produced by folic acid (0.072 μg·g(-1)·day(-1), p.o., 2 weeks) per se and in combination. Male Wistar rats were exposed to methotrexate (0.35 mg·kg(-1)·day(-1), i.p.) for 2 weeks to induce endothelial dysfunction. Methotrexate exposure led to shedding of endothelium, decreased vascular reactivity, increased oxidative stress, decreased serum nitrite levels, and increase in aortic collagen deposition. Curcumin (200 mg·kg(-1)·day(-1) and 400 mg·kg(-1)·day(-1), p.o.) for 4 weeks prevented the increase in oxidative stress, decrease in serum nitrite, aortic collagen deposition, and also vascular reactivity. The effects were comparable with those produced by folic acid therapy. The study shows that curcumin, when concomitantly administered with methotrexate, abrogated its vascular side effects by preventing an increase in oxidative stress and abating any reduction in physiological nitric oxide levels.
authors.affiliation: Bombay College of Pharmacy, Department of Pharmacology, University of Mumbai, 400098 Mumbai, India.|Bombay College of Pharmacy, Department of Pharmacology, University of Mumbai, 400098 Mumbai, India.
authors.forename: Himanshu
authors.initials: H
authors.lastname: Sankrityayan
authors.affiliation: Bombay College of Pharmacy, Department of Pharmacology, University of Mumbai, 400098 Mumbai, India.|Bombay College of Pharmacy, Department of Pharmacology, University of Mumbai, 400098 Mumbai, India.
authors.forename: Anuradha S
authors.initials: AS
authors.lastname: Majumdar
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D003094:Collagen / Q000378:metabolism; D003474:Curcumin / Q000008:administration & dosage*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D005492:Folic Acid / Q000008:administration & dosage*; D005978:Glutathione / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008727:Methotrexate / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D009573:Nitrites / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000097:blood; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000975:Antioxidants; D009573:Nitrites; D008315:Malondialdehyde; D003094:Collagen; D005492:Folic Acid; D013482:Superoxide Dismutase; D005978:Glutathione; D003474:Curcumin; D008727:Methotrexate
keywords: acide folique; curcumin; curcumine; dysfonction endothéliale vasculaire; folic acid; methotrexate; méthotrexate; nitric oxide; oxidative stress; oxyde nitrique; stress oxydant; vascular endothelial dysfunction