The protective effect of 2-mercaptoethane sulfonate (MESNA) against traumatic brain injury in rats.
BACKGROUND
The agent, 2-mercaptoethane sulfonate (MESNA), is a synthetic small molecule, widely used as a systemic protective agent against chemotherapy toxicity, but is primarily used to reduce hemorrhagic cystitis induced by cyclophosphamide. Because MESNA has potential antioxidant and cytoprotective effects, so we hypothesized that MESNA may protect the brain against traumatic injury.


METHODS
Thirty-two rats were randomized into four groups of eight animals each; Group 1 (sham), Group 2 (trauma), Group 3 (150 mg/kg MESNA), Group 4 (30 mg/kg methylprednisolone). Only skin incision was performed in the sham group. In all the other groups, the traumatic brain injury model was created by an object weighing 450 g falling freely from a height of 70 cm through a copper tube on to the metal disc over the skull. The drugs were administered immediately after the injury. The animals were killed 24 h later. Brain tissues were extracted for analysis, where levels of tissue malondialdehyde, caspase-3, glutathione peroxidase, superoxide dismutase, nitric oxide, nitric oxide synthetase and xanthine oxidase were analyzed. Also, histopathological evaluation of the tissues was performed.


RESULTS
After head trauma, tissue malondialdehyde levels increased; these levels were significantly decreased by MESNA administration. Caspase-3 levels were increased after trauma, but no effect of MESNA was determined in caspase-3 activity. Following trauma, both glutathione peroxidase and superoxide dismutase levels were decreased; MESNA increased the activity of both these antioxidant enzymes. Also, after trauma, nitric oxide, nitric oxide synthetase and xanthine oxidase levels were increased; administration of MESNA significantly decreased the levels of nitric oxide, nitric oxide synthetase and xanthine oxidase, promising an antioxidant activity. Histopathological analysis showed that MESNA protected the brain tissues well from injury.


CONCLUSIONS
Although further studies considering different dose regimens and time intervals are required, MESNA was shown to be at least as effective as methylprednisolone in the traumatic brain injury model.
Neurosurgery Clinic, Diskapi Yildirim Beyazit Education and Research Hospital, Ministry of Health, Ankara, Turkey.
Erdal Resit
ER
Yilmaz
Hayri
H
Kertmen
Bora
B
Gürer
Mehmet Ali
MA
Kanat
Ata Türker
AT
Arikok
Berrin Imge
BI
Ergüder
Askin Esen
AE
Hasturk
Julide
J
Ergil
Zeki
Z
Sekerci
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D004195:Disease Models, Animal; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D015080:Mesna / Q000627:therapeutic use*; D008775:Methylprednisolone / Q000627:therapeutic use; D018384:Oxidative Stress / Q000502:physiology; D020011:Protective Agents / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D020011:Protective Agents; D015080:Mesna; D008775:Methylprednisolone