Nitric oxide pros and cons: The role of L-arginine, a nitric oxide precursor, and idebenone, a coenzyme-Q analogue in ameliorating cerebral hypoxia in rat.
Evidence exists that nitric oxide (NO) may mediate both protective and pathological responses during brain hypoxia (HP). Reactive oxygen species have also been implicated in the pathophysiological response of the brain tissues to HP. Therefore, this study investigated whether a NO precursor, l-arginine (l-arg), a free radical scavenger, idebenone (ID), and their combination would reduce neurological injury resulting from hemic hypoxia (HP) in rats. Adult male Wistar albino rats were injected with sodium nitrite (60 mg/kg, s.c.) to establish hemic hypoxia. ID (100 mg kg(-1), i.p.) and/or l-arg (100 mg kg(-1), i.p.) were administrated 24 and 1h prior to sodium nitrite intoxication, respectively. Hypoxia significantly decreased hemoglobin concentration, while significantly increased serum lactate dehydrogenase (LDH), creatine phosphokinase (CPK), total nitrate/nitrite, sialic, and uric acids concentrations. Moreover, brain lipid peroxides were significantly enhanced, while reduced glutathione, l-ascorbic acids, adenosine triphosphate (ATP) contents, and the activities of catalase and superoxide dismutase, were significantly reduced in the brain tissue. Pretreatment with either ID or l-arg altered the majority of the above-mentioned biochemical changes in hypoxic rats. Additionally, the combination of these two agents significantly reduced injury marker enzyme activities as well as serum sialic, and uric acids level (P>0.05 vs. control). Moreover, this combination exerted a synergistic antioxidant effect by blocking the induction of lipid peroxidation, preserving brain energy (ATP) content, and greatly reducing the hypoxic alterations in brain enzymatic and non-enzymatic antioxidants. Histopathological examination of the brain tissue supported these biochemical findings. This study showed that ID and l-arg were capable of reducing neurological injury following HP in rat, and support the idea of the usefulness of l-arg and ID as prophylaxis from hypoxic brain injury.
Abdel Baky
Nayira A
NA
Pharmacology Department, Faculty of Pharmacy, King Saud University, Riyadh, Saudi Arabia. nayiraabdelbaky@yahoo.com
Zaidi
Zeenat F
ZF
Fatani
Amal J
AJ
Sayed-Ahmed
Mohamed M
MM
Yaqub
Hazar
H
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001120:Arginine / Q000627:therapeutic use*; D001921:Brain / Q000473:pathology; D002374:Catalase / Q000378:metabolism; D003402:Creatine Kinase / Q000097:blood; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005911:Gliosis / Q000209:etiology; D006454:Hemoglobins / Q000378:metabolism; D002534:Hypoxia, Brain / Q000139:chemically induced / Q000150:complications / Q000517:prevention & control*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D009422:Nervous System Diseases / Q000188:drug therapy / Q000209:etiology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D009566:Nitrates / Q000009:adverse effects*; D009569:Nitric Oxide / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000975:Antioxidants; D004338:Drug Combinations; D006454:Hemoglobins; D009566:Nitrates; D014451:Ubiquinone; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; C031618:sodium nitrate; D001120:Arginine; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D013482:Superoxide Dismutase; D003402:Creatine Kinase; C036619:idebenone