title: Nitrous oxide related behavioral and histopathological changes may be related to oxidative stress.
abstract: Nitrous oxide (N₂O) toxicity can result in myelin loss and hyperhomocysteinemia similar to cobalamin (Cbl) deficiency. Studies on N₂O exposure can help in understanding the mechanism of demyelination. In view of paucity of studies on N₂O toxicity in rats this study was undertaken. Six male wistar rats were exposed to 1.5L/min N₂O with 1:1 O₂ for 90 min daily for 1 month. After 1-month exposure blood homocysteine (HCY) and oxidative stress parameters glutathione (GSH) and total antioxidant capacity (TAC) were measured. Brain and spinal cord was subjected to histopathological examination. The neurobehavioral changes, oxidative stress parameters and histopathological changes were correlated with serum B12 and HCY level. After 1-month exposure, the rats appeared sluggish, lethargic and developed predominantly hind limb weakness for 1-1.5h. In the exposed group, the total distance traveled (2001.66 ± 118.27 cm; p=0.037), time moving (80.16 ± 5.7s; p=0.028), number of rearing (10.33 ± 1.45; p=0.014) and grip strength (1042.40 ± 51.3N; p=0.041) were significantly decreased whereas, resting time significantly increased (219.83 ± 5.7s; p=0.030) compared to controls. Serum HCY level was significantly increased (20.56 ± 1.296 μm/ml; p=0.0007) in the exposed group. However, serum B12 and folic acid levels were not significantly different. GSH significantly decreased (2.21 ± 0.60 mg/dl; p=0.018) along with TAC (0.76 ± 0.16 Trolox_Eq_mmol/l; p=0.036). The histopathological studies revealed shrinkage and vacuolation of neurons in cerebral cortex, focal myelin loss, vacuolation in subcortical white matter and spinal cord. N₂O exposure results in behavioral alterations, hyperhomocysteinemia, cortical and spinal cord demyelination which were associated with decrease GSH and TAC highlighting pathophysiological role of oxidative stress.
authors.affiliation: Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Sandeep Kumar
authors.initials: SK
authors.lastname: Singh
authors.affiliation: Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India. Electronic address: drukmisra@rediffmail.com.
authors.forename: Usha Kant
authors.initials: UK
authors.lastname: Misra
authors.affiliation: Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Jayantee
authors.initials: J
authors.lastname: Kalita
authors.affiliation: Central Drug Research Institute (CDRI), Lucknow, India.
authors.forename: Himangsu K
authors.initials: HK
authors.lastname: Bora
authors.affiliation: Indian Institute of Toxicology Research (IITR), Lucknow, India.
authors.forename: Ramesh C
authors.initials: RC
authors.lastname: Murthy
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D003711:Demyelinating Diseases / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D004195:Disease Models, Animal; D005978:Glutathione / Q000097:blood; D006710:Homocysteine / Q000097:blood; D020138:Hyperhomocysteinemia / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D008297:Male; D009043:Motor Activity; D053580:Muscle Strength; D009609:Nitrous Oxide; D018384:Oxidative Stress / Q000187:drug effects; D017208:Rats, Wistar; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D014805:Vitamin B 12 / Q000097:blood; D014806:Vitamin B 12 Deficiency / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology / Q000523:psychology
chemical_list: D000975:Antioxidants; D006710:Homocysteine; D005978:Glutathione; D009609:Nitrous Oxide; D014805:Vitamin B 12
keywords: Cobalamin; Homocysteine; Hyperhomocysteinemia; Myelin loss; Nitrous oxide