Neuroprotective effects of aqueous extract of Carica papaya, vitamin E and dexamethasone on traumatic brain injury-induced oxidative damage in adult male Wistar rats.

Samenvatting

Background: Traumatic brain injury, TBI (blunt or penetrating) induces oxidative stress by generation of free radicals which triggers a cascade of events resulting in cellular dysfunctions and death. The neuroprotective effects of ripe aqueous extract of Carica papaya (paw-paw) (CP) fruit, vitamin E and dexamethasone, respectively, on traumatized cerebral cortex of Wistar rats was studied.

Method: Fifty adult male Wistar rats were divided into six groups; control, trauma control (TC), Carica papaya control (CPC), Carica papaya+trauma (CPT), vitamin E+ trauma (VET) and
dexamethasone+trauma (DET) groups. Two hundred (200) mg/kg body weight of CP and vitamin E were administered orally, while dexamethasone was administered at 0.005 ml of 4 mg/ml intraperitoneally. Rats were treated for 14 days pre-trauma induction and sacrificed 7 days post-trauma. Body, brain and cerebral weights as well as the behaviour of the rats were studied. Blood and brain tissues were processed for haematological parameters, oxidative stress markers and histomorphological evaluations.

Results: A decreased body weight was seen in all the traumatized rats compared with the control rats (p<0.05). Increased body weight was observed in the CPC, CPT and VET rats, respectively, compared with the TC rats (p<0.05). An increased brain weight was observed in the TC and VET rats compared with the control rats at p<0.05. In behavioural studies, trauma significantly (p<0.05) reduced the hang time (forelimb grip) and delayed time of re-orientation (negative geotaxis). Carica papaya and DET increased the time of re-orientation. A decreased percentage lymphocyte in the DET rats and an increased percentage neutrophil was seen in the TC and DET rats compared with the control rats at p<0.05. An increased levels of hydrogen peroxide (H2O2
) and lipid peroxidation (LPO) were seen in the TC and DET rats at p<0.05. Carica papaya extracts and VET significantly increased the percentage lymphocytes and decreased neutrophil accumulation; they also increased H2O2 levels and LPO compared with the control rats at p<0.05. Cerebral cortical thickness was reduced in the TC and DET groups
compared with the control rats at p<0.05. Carica papaya improved cortical thickness. Dexamethasonetreated rats showed severe distortion of the cerebral cortical layers, while the TC rats (penetrating) showed haemorrhage, vascular infiltration and congestion, and darkly stained (pyknotic) bodies.

Conclusion: Carica papaya fruit extracts and vitamin E appeared to protect the brain against TBI-induced oxidative stress. Dexamethasone however, aggravated the oxidative stress when compared to the TC group as such may not be neuroprotective.

Keywords: Traumatic brain injury, Oxidative stress, Cerebral cortex, Carica papaya, vitamin E, Dexamethasone

Résumé
Contexte: La lésion cérébrale traumatique, LCT (émoussée ou pénétrante) induit un stress oxydatif par la génération de radicaux libres qui déclenche une cascade d’événements entraînant des dysfonctionnements cellulaires et la mort. On a étudié les effets neuro-protecteurs de l’extrait aqueux mûr de fruits de Carica papaya (papaye) (CP), de vitamine E et de dexamethasone, respectivement, sur le cortex cérébral traumatique des rats Wistar.

Méthode: Cinquante rats Wistar mâles adultes ont été divisés en six groupes; le contrôle, contrôle de trauma (CT), le contrôle de carica papaya (CCP), carica papaya + trauma (CPT), la vitamine E +
traumatisme (VET) et les groupes dexaméthasone + trauma (DET). Deux cent (200) mg / kg de poids  corporel de CP et de vitamine E ont été administrés par voie orale, tandis que la dexaméthasone a été administrée à 0,005 ml de 4 mg / ml par voie intra-péritonéale. Les rats ont été traités pendant 14 jours d’induction pré-traumatique et sacrifiés 7 jours après le traumatisme. Lespoids corporels, cervicaux et cérébraux ainsi que le comportement des rats ont été étudiés. Le sang et les tissus cérébraux ont été traités pour des paramètres hématologiques, des marqueurs de stress oxydatif et des évaluations histomorphologiques.

Résultats: Une diminution du poids corporel a été observée chez tous les rats traumatisés par rapport aux rats témoins (p <0,05). On a observé une augmentation du poids corporel chez les rats CCP, CPT et VET, respectivement, comparativement aux rats CT (p <0,05). Une augmentation du poids du cerveau a été observée chez les rats CT et VET comparativement aux rats témoins à p <0,05. Dans les études comportementales, le traumatisme a significativement diminué (p <0,05) le temps de suspension (prise d’avant-bras) et le délai de réorientation (géotaxie négative). Carica papaya et DET augmentent le temps de réorientation. Une diminution du pourcentage de lymphocytes chez les rats DET et une augmentation du pourcentage de neutrophiles ont été observées chez les rats CT et DET par rapport aux rats témoins à p <0,05. Des concentrations accrues de peroxyde d’hydrogène (H2O2 ) et de peroxydation lipidique (POL) ont été observées chez les rats CT et DET à p <0,05. Les extraits de carica papaya et le VET ont significativement augmenté le pourcentage de lymphocytes et diminué l’accumulation de neutrophiles; Ils
ont également augmenté les niveaux de H2O2  et POL par rapport aux rats de contrôle à pÂ0,05. L’épaisseur corticale cérébrale a été réduite dans les groupes CT et DET par rapport aux rats témoins à p <0,05. Carica papaya a amélioré l’épaisseur corticale. Les rats traités par la dexaméthasone présentaient une distorsion sévère des couches corticales cérébrales, alors que les rats CT (pénétrants) présentaient une hémorragie, une infiltration vasculaire et une congestion, et des corps sombres (pycnotiques).

Conclusion: Les extraits de fruits de carica papaya et de vitamine E ont paru protéger le cerveau contre le stress oxydatif induit par les LCT. Cependant, la dexaméthasone a aggravé le stress oxydatif par rapport au groupe CT, car elle peut ne pas être neuro-protectrice.

Mots-clés: Lésion cérébrale traumatique, stress oxydatif, cortex cérébral, carica papaya, vitamine E, dexaméthasone

Correspondence: Prof. A.O. Malomo, Department of Surgery and Anatomy, College of Medicine, University of Ibadan, Ibadan, Nitgeria. E-mail: ademalomo@yahoo.com.

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