Possible nitric oxide modulation in the protective effects of rutin against experimental head trauma-induced cognitive deficits: behavioral, biochemical, and molecular correlates.
BACKGROUND
Traumatic head injury is turning out to be a major cause of disability and death. Nitric oxide (NO), an intercellular messenger plays a crucial role in the pathophysiology of several neurologic disorders. Therefore, the present study was designed to investigate the effects of rutin, a well-known flavonoid against cognitive deficits and neuroinflammation associated with traumatic head injury and the probable role of NO pathway in this effect.


METHODS
Wistar rats were exposed to head trauma using weight drop method and kept for a postsurgical rehabilitation period of 2 wk. Later, animals were administered with rutin (20, 40, and 80 mg/kg; per oral) alone and in combination with NO modulators such as N(G)-nitro-L-arginine methyl ester and L-arginine, daily for another 2 wk.


RESULTS
Head injury caused impaired spatial navigation in Morris water maze test and poor retention in elevated plus maze task. Furthermore, there was a significant rise in acetylcholinesterase activity, oxidative stress, neuroinflammation (tumor necrosis factor α), and neuronal apoptosis (caspase-3) in both cortex and hippocampal regions of traumatized rat brain. Rutin significantly attenuated these behavioral, biochemical, and molecular alterations associated with head trauma. Furthermore, pretreatment of N(G)-nitro-L-arginine methyl ester (10 mg/kg, intraperitoneally), a nonspecific nitric oxide synthase inhibitor, with subeffective dose of rutin (40 mg/kg) potentiated the protective effects; however, pretreatment of L-arginine (100 mg/kg; intraperitoneally), an NO donor, reversed the effects of rutin.


CONCLUSIONS
The present study suggests that NO modulation could possibly be involved in the neuroprotective effects of rutin against head trauma-induced cognitive deficits, neuroinflammation, and apoptotic signaling cascade.
Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh, India. Electronic address: kumaruips@rediffmail.com.
Anil
A
Kumar
Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh, India.
Puneet
P
Rinwa
Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh, India.
Hitesh
H
Dhar
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001120:Arginine; D001921:Brain / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D003072:Cognition Disorders / Q000209:etiology / Q000517:prevention & control*; D006259:Craniocerebral Trauma / Q000150:complications / Q000188:drug therapy*; D004353:Drug Evaluation, Preclinical; D005978:Glutathione / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012431:Rutin / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018696:Neuroprotective Agents; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D012431:Rutin; D001120:Arginine; D002374:Catalase; D000110:Acetylcholinesterase; C505410:Casp3 protein, rat; D053148:Caspase 3; D005978:Glutathione; D019331:NG-Nitroarginine Methyl Ester
Apoptosis; Cognitive dysfunction; Head trauma; Neuroinflammation; Nitric oxide