Research Article
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Protective Mechanism of Morus nigra on Carbon Tetrachloride Induced Brain Damage in Rats

Year 2017, Volume: 2 Issue: 2, 97 - 108, 29.12.2017
https://doi.org/10.24880/maeuvfd.341661

Abstract



Morus nigra (MN) is a common
fruit used all over the world.
Hepatic encephalopathy (HE) is a
dangerous neuropsychiatric complication of both acute and chronic liver
failure, and is the most common cause of death in patients with end-stage liver
disease.
To our knowledge, this is the first study investigated the efficiencies of MN on the treatment of HE on cirrhotic rat liver model induced
by
carbon
tetrachloride
(CCI4). In
this study it has been used
superoxide dismutase (SOD)
and catalase (CAT)
activities assays, 8-hydroxydeoxyguanosine (8-OHdG) immunohistochemistry and Haematoxylin-Eosin (H&E) staining in the brain, as well as aspartate aminotransferase (AST) and alanine
aminotransferase
(ALT) levels in liver tissue With this aim, 42 Sprague-Dawley male rats were divided into six groups: control, HE
control (
1 mL/kg CCI4/twice a week,
intraperitoneal
), 125 mg/kg MN, 250 mg/kg MN, CCI4+125 mg/kg MN and CCI4+250 mg/kg MN groups. CCl4 caused a significant increase in serum enzyme levels in
rat livers, compared with control. On the other hand, MN treatment restored the
biochemical parameters significantly in a dose-dependent manner. 8-OHdG
activity was significantly increased in CCI4 group. However, these
increases were significantly decreased by MN treatment.
While intraperitoneal administration
of MN significantly reduced oxidative stress, prevented apoptosis and caused an
increase in the antioxidant defence mechanism activity in brain compared to the
control group.
 Brains of rats treated with MN showed less DNA damage
than treated groups with CCI4.
As a
result of t
his
study showed that MN has a neuroprotective effect because of its
anti-inflammatory, anti-apoptotic, antioxidant properties.




References

  • 1. Butterworth RF. Hepatic encephalopathy: a neuropsychiatric disorder involving multiple neurotransmitter systems. Cur Op Neurol. 2000;13:721–727.
  • 2. Jalan R, Olde Damink SW, Hayes PC, Deutz NE, Lee A. Pathogenesis of intracranial hypertension in acute liver failure: inflammation, ammonia and cerebral blood flow. J Hepatol. 2004;41:613–20.
  • 3. Rama Rao KV, Norenberg MD. Brain energy metabolism and mitochondrial dysfunction in acute and chronic hepatic encephalopathy. Neurochem Int. 2012;60:697–706.
  • 4. Bosoi CR, Rose CF. Oxidative stress: a systemic factor implicated in the pathogenesis of hepatic encephalopathy. Metab Brain Dis. 2013;28:175–8.
  • 5. Basu, S., Carbon tetrachloride-induced lipid peroxidation: eicosanoid formation and their regulation by antioxidant nutrients. Toxicology. 2003; 189, 113– 127.
  • 6. Dani, C., Pasquali, M.A.B., Oliveira, M.R., Umezu, F.M., Salvador, M., Henriques, J.A.P., Moreira, J.C.F., Protective effects of purple grape juice on carbon tetrachloride-induced oxidative stress in brains of adult Wistar rats. J. Med. Food 2008; 11, 55–61.
  • 7. Botsoglou, N.A., Taitzoglou, I.A., Botsoglou, E., Lavrentiadou, S., Kokoli, A.N., Roubies, N., Effect of long-term dietary administration of oregano on the alleviation of carbon tetrachloride -induced oxidative stress in rats. J. Agric. Food Chem. 2008; 56, 6287–6293.
  • 8. Nomura, T. and Hano, Y., Isoprenoid-substituted phenolic compounds of moraceous plants. Natural Product Reports, 1994; 11, 2, 205-218. PMid:15209130. http://dx.doi.org/10.1039/np9941100205.
  • 9. J. R. G. D. S. Almeida, A. L. Guimarães, A. P. de Oliveira et al., “Evaluation of hypoglycemic potential and pre-clinical toxicology of Morus nigra l. (Moraceae),” Latin American Journal of Pharmacy, 2011;30, 1, 96–100.
  • 10. G. R. Souza, R. G. Oliveira-Junior, T. C. Diniz , A. Branco, S. R. G. Lima-Saraiva et al., Braz. J. Biol., ahead of print Epub Aug 17, 2017: Assessment of the antibacterial, cytotoxic and antioxidant activities of Morus nigra L. (Moraceae). Brazilian Journal of Biology. 1678-4375. doi.org/10.1590/1519-6984.05316
  • 11. Mecocci P, Polidori MC. Antioxidant clinical trials in mild cognitive impairment and Alzheimer's disease. Biophys. Acta. 2012;1822:631–638. 12. J. R. G. D. S. Almeida, A. L. Guimarães, A. P. de Oliveira et al., “Evaluation of hypoglycemic potential and pre-clinical toxicology of Morus nigra l. (Moraceae),” Latin American Journal of Pharmacy, 2011;30, 1, 96–100
  • 13. Abd El-Mawla A. M. A., Mohamed K. M., Mostafa A. M. Induction of biologically active flavonoids in cell cultures of Morus nigra and testing their hypoglycemic efficacy. Scientia Pharmaceutica. 2011;79(4):951–961. doi: 10.3797/scipharm.1101-1106.
  • 14. Dalmagro AP1,2, Camargo A2, Zeni ALB3,4. Morus nigra and its major phenolic, syringic acid, have antidepressant-like and neuroprotective effects in mice. Metab Brain Dis. 2017 Aug 18. doi: 10.1007/s11011-017-0089-y.
  • 15. Bémeur C, Butterworth RF (2013) Liver-brain proinflammatory signalling in acute liver failure: role in the pathogenesis of hepatic encephalopathy and brain edema. Metab Brain Dis 28:145–150. doi:10.1007/s11011-012-9361-3
  • 16. Coballase-Urrutia E., Pedraza-Chaverri J., Cárdenas-Rodríguez N., Huerta-Gertrudis B., García-Cruz M.E., Ramírez-Morales A., Sánchez-González D.J., Martínez-Martínez C.M., Camacho-Carranza R., Espinosa-Aguirre J.J. Hepatoprotective effect of acetonic and methanolic extracts of Heterothecainuloides against CCl (4)-induced toxicity in rats. Exp. Toxicol. Pathol. 2011;63:363–370.
  • 17. M. Bagchi, S. Ghosh, D. Bagchi, E. Hassoun, S.J. Stohs, Protective effects of lazaroid U74389F (16-desmethyl tirilazad) on endrin-induced lipid peroxidation and DNA damage in brain and liver and regional distribution of catalase activity in rat brain, Free Radic Biol Me. 19 (6) (1995) 867–872.
  • 18. Khan RA. Protective effect of Launaea procumbens (L.) on lungs against CCl4-induced pulmonary damages in rat. BMC Complement Altern Med 2012; 12:133.
  • 19. Ahmad B, Khan MR, Shah NA. Amelioration of carbon tetrachloride-induced pulmonary toxicity with Oxalis corniculata. Toxicol Ind Health 2015; 31:1243-1251.
  • 20. Korhonen R, Lahti A, Kankaanranta H, Moilanen E. Nitric oxide production and signaling in inflammation. Curr Drug Targets Inflamm Allergy. 2005;4(4):471–479.
  • 21. Boots A.W., Kubben N., Haenen G.R., Bast A. Oxidized quercetin reacts with thiols rather than with ascorbate: implication for quercetin supplementation. Biochem. Biophys. Res. Commun. 2003;308:560–565.
  • 22. Lotito S.B., Frei B. Consumption of flavonoid-rich foods and increased plasma antioxidant capacity in humans: cause, consequence, or epiphenomenon? Free Radical Biol. Med. 2006;41:1727–1746.
  • 23. A.R.T.Silva,A.C.F.Santos,J.M.Farfeletal.,“Repairofoxidative DNA damage, cell-cycle regulation and neuronal death may influence the clinical manifestation of Alzheimer’s disease,” PLoSONE,vol.9,no.6,ArticleIDe99897,2014.
  • 24. Acharya C, Wade JB, Fagan A, White M, Gavis E, Ganapathy D, Gilles H, Heuman DM, Bajaj JS. Overt Hepatic Encephalopathy impairs learning on the Encephalapp Stroop which is Reversible after Liver Transplant. Liver Transpl. 2017. doi: 10.1002/lt.24864.

Sıçanlarda Karbon Tetraklorür İle Uyarılmış Beyin Hasarında Morus nigra'nın Koruyucu Mekanizması

Year 2017, Volume: 2 Issue: 2, 97 - 108, 29.12.2017
https://doi.org/10.24880/maeuvfd.341661

Abstract



Morus
nigra
(MN) tüm dünyada yaygın olarak
kullanılan bir meyvedir. Hepatik ensefalopati (HE) hem akut hem de kronik
karaciğer yetmezliğinde tehlikeli bir nöropsikiyatrik komplikasyondur ve son
dönem karaciğer hastalığı olan hastalarda en sık görülen ölüm nedenidir. Bilgimize göre bu, karbon
tetraklorür (CCI4) ile indüklenen sirozlu sıçan karaciğeri modeli
üzerinde HE tedavisinde MN’nin etkilerinin araştırıldığı ilk çalışmadır. Bu
çalışmada,
karaciğer
dokusunda
aspartat aminotransferaz (AST) ve alanin aminotransferaz (ALT) seviyelerinin yanısıra beyin dokusunda 8-hidroksideoksiguanozin (8-OHdG) imünohistokimya ve Hematoksilen-eozin
boyaması
, superoksid dismutaz (SOD) ve katalaz (CAT) aktivite testleri kullanıldı. Bu amaçla 42 Spraque-Dawley erkek sıçan 6 gruba ayrıldı:  kontrol, HE kontrol (1 mL/kg CCI4/haftada 2, intraperitonal), 125 mg/kg MN, 250 mg/kg MN, CCI4+125 mg/kg MN ve CCI4+250
mg/kg MN
grupları. CCI4 sıçan karaciğerlerinde kontrol ile karşılaştırıldığında
serum enzim seviyelerinde belirgin bir artışa sebep oldu. Diğer taraftan MN uygulaması
biyokimyasal parametreleri doza bağımlı olarak önemli ölçüde düzeltti. 8-OHdG aktivitesi
CCI4 grubunda belirgin olarak arttı. Ancak MN tedavisi ile bu
artışlar önemli ölçüde azaldı. MN'nin intraperitoneal olarak uygulanması, kontrol
grubuna kıyasla oksidatif stresi önemli ölçüde azaltırken, apoptozisi önledi ve
beyindeki antioksidan savunma mekanizması aktivitesinde artışa neden oldu. MN
ile tedavi edilen sıçan beyinleri
CCI4 ile tedavi edilen sıçanlara göre daha az DNA hasarı
gösterdi. Bu çalışmanın sonucu MN'nin anti-inflamatuar, antiapoptotik,
antioksidan özelliklerinden dolayı nöroprotektif etkiye sahip olduğunu
gösterdi.




References

  • 1. Butterworth RF. Hepatic encephalopathy: a neuropsychiatric disorder involving multiple neurotransmitter systems. Cur Op Neurol. 2000;13:721–727.
  • 2. Jalan R, Olde Damink SW, Hayes PC, Deutz NE, Lee A. Pathogenesis of intracranial hypertension in acute liver failure: inflammation, ammonia and cerebral blood flow. J Hepatol. 2004;41:613–20.
  • 3. Rama Rao KV, Norenberg MD. Brain energy metabolism and mitochondrial dysfunction in acute and chronic hepatic encephalopathy. Neurochem Int. 2012;60:697–706.
  • 4. Bosoi CR, Rose CF. Oxidative stress: a systemic factor implicated in the pathogenesis of hepatic encephalopathy. Metab Brain Dis. 2013;28:175–8.
  • 5. Basu, S., Carbon tetrachloride-induced lipid peroxidation: eicosanoid formation and their regulation by antioxidant nutrients. Toxicology. 2003; 189, 113– 127.
  • 6. Dani, C., Pasquali, M.A.B., Oliveira, M.R., Umezu, F.M., Salvador, M., Henriques, J.A.P., Moreira, J.C.F., Protective effects of purple grape juice on carbon tetrachloride-induced oxidative stress in brains of adult Wistar rats. J. Med. Food 2008; 11, 55–61.
  • 7. Botsoglou, N.A., Taitzoglou, I.A., Botsoglou, E., Lavrentiadou, S., Kokoli, A.N., Roubies, N., Effect of long-term dietary administration of oregano on the alleviation of carbon tetrachloride -induced oxidative stress in rats. J. Agric. Food Chem. 2008; 56, 6287–6293.
  • 8. Nomura, T. and Hano, Y., Isoprenoid-substituted phenolic compounds of moraceous plants. Natural Product Reports, 1994; 11, 2, 205-218. PMid:15209130. http://dx.doi.org/10.1039/np9941100205.
  • 9. J. R. G. D. S. Almeida, A. L. Guimarães, A. P. de Oliveira et al., “Evaluation of hypoglycemic potential and pre-clinical toxicology of Morus nigra l. (Moraceae),” Latin American Journal of Pharmacy, 2011;30, 1, 96–100.
  • 10. G. R. Souza, R. G. Oliveira-Junior, T. C. Diniz , A. Branco, S. R. G. Lima-Saraiva et al., Braz. J. Biol., ahead of print Epub Aug 17, 2017: Assessment of the antibacterial, cytotoxic and antioxidant activities of Morus nigra L. (Moraceae). Brazilian Journal of Biology. 1678-4375. doi.org/10.1590/1519-6984.05316
  • 11. Mecocci P, Polidori MC. Antioxidant clinical trials in mild cognitive impairment and Alzheimer's disease. Biophys. Acta. 2012;1822:631–638. 12. J. R. G. D. S. Almeida, A. L. Guimarães, A. P. de Oliveira et al., “Evaluation of hypoglycemic potential and pre-clinical toxicology of Morus nigra l. (Moraceae),” Latin American Journal of Pharmacy, 2011;30, 1, 96–100
  • 13. Abd El-Mawla A. M. A., Mohamed K. M., Mostafa A. M. Induction of biologically active flavonoids in cell cultures of Morus nigra and testing their hypoglycemic efficacy. Scientia Pharmaceutica. 2011;79(4):951–961. doi: 10.3797/scipharm.1101-1106.
  • 14. Dalmagro AP1,2, Camargo A2, Zeni ALB3,4. Morus nigra and its major phenolic, syringic acid, have antidepressant-like and neuroprotective effects in mice. Metab Brain Dis. 2017 Aug 18. doi: 10.1007/s11011-017-0089-y.
  • 15. Bémeur C, Butterworth RF (2013) Liver-brain proinflammatory signalling in acute liver failure: role in the pathogenesis of hepatic encephalopathy and brain edema. Metab Brain Dis 28:145–150. doi:10.1007/s11011-012-9361-3
  • 16. Coballase-Urrutia E., Pedraza-Chaverri J., Cárdenas-Rodríguez N., Huerta-Gertrudis B., García-Cruz M.E., Ramírez-Morales A., Sánchez-González D.J., Martínez-Martínez C.M., Camacho-Carranza R., Espinosa-Aguirre J.J. Hepatoprotective effect of acetonic and methanolic extracts of Heterothecainuloides against CCl (4)-induced toxicity in rats. Exp. Toxicol. Pathol. 2011;63:363–370.
  • 17. M. Bagchi, S. Ghosh, D. Bagchi, E. Hassoun, S.J. Stohs, Protective effects of lazaroid U74389F (16-desmethyl tirilazad) on endrin-induced lipid peroxidation and DNA damage in brain and liver and regional distribution of catalase activity in rat brain, Free Radic Biol Me. 19 (6) (1995) 867–872.
  • 18. Khan RA. Protective effect of Launaea procumbens (L.) on lungs against CCl4-induced pulmonary damages in rat. BMC Complement Altern Med 2012; 12:133.
  • 19. Ahmad B, Khan MR, Shah NA. Amelioration of carbon tetrachloride-induced pulmonary toxicity with Oxalis corniculata. Toxicol Ind Health 2015; 31:1243-1251.
  • 20. Korhonen R, Lahti A, Kankaanranta H, Moilanen E. Nitric oxide production and signaling in inflammation. Curr Drug Targets Inflamm Allergy. 2005;4(4):471–479.
  • 21. Boots A.W., Kubben N., Haenen G.R., Bast A. Oxidized quercetin reacts with thiols rather than with ascorbate: implication for quercetin supplementation. Biochem. Biophys. Res. Commun. 2003;308:560–565.
  • 22. Lotito S.B., Frei B. Consumption of flavonoid-rich foods and increased plasma antioxidant capacity in humans: cause, consequence, or epiphenomenon? Free Radical Biol. Med. 2006;41:1727–1746.
  • 23. A.R.T.Silva,A.C.F.Santos,J.M.Farfeletal.,“Repairofoxidative DNA damage, cell-cycle regulation and neuronal death may influence the clinical manifestation of Alzheimer’s disease,” PLoSONE,vol.9,no.6,ArticleIDe99897,2014.
  • 24. Acharya C, Wade JB, Fagan A, White M, Gavis E, Ganapathy D, Gilles H, Heuman DM, Bajaj JS. Overt Hepatic Encephalopathy impairs learning on the Encephalapp Stroop which is Reversible after Liver Transplant. Liver Transpl. 2017. doi: 10.1002/lt.24864.
There are 23 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Research Articles
Authors

Gülşah Yıldız Deniz

Publication Date December 29, 2017
Submission Date October 4, 2017
Published in Issue Year 2017 Volume: 2 Issue: 2

Cite

APA Yıldız Deniz, G. (2017). Protective Mechanism of Morus nigra on Carbon Tetrachloride Induced Brain Damage in Rats. Veterinary Journal of Mehmet Akif Ersoy University, 2(2), 97-108. https://doi.org/10.24880/maeuvfd.341661