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Published August 28, 2023 | Version v1
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Efeito da melatonina na histofisiologia do fígado de ratos adolescentes expostos ao álcool

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  • 1. Núcleo do Conhecimento

Description

O presente estudo avaliou se a administração de melatonina durante a adolescência pode prevenir os efeitos prejudiciais produzidos pelo álcool no fígado. Trinta ratos albinos (Rattus norvegicus albinus), fêmeas, com 40 dias de idade, virgens, pesando aproximadamente 150±10g, da linhagem Wistar, foram divididas nos seguintes grupos: I – Ratos adolescentes que não receberam álcool e foram sacrificadas aos 60 dias de vida; II – Ratos adolescentes submetidas ao consumo crônico de álcool e sacrificadas aos 60 dias de vida; III – Ratos adolescentes submetidas ao consumo crônico de álcool e simultaneamente tratadas com melatonina, e sacrificadas aos 60 dias de vida. Os órgãos coletados passaram por processamento histológico e, para obter os resultados, foram realizadas análises morfométricas, histopatológicas e histoquímicas. O álcool foi administrado por gavagem, por injeção intragástrica, na dose de 3 g/Kg de álcool etílico nos ratos dos grupos II e III, por 20 dias. A melatonina foi administrada em injeções diárias de 0,8 mg/Kg, sempre no início da noite, intraperitonealmente, por 20 dias. Ao analisar o peso dos animais, não foi observada diferença significativa entre os grupos. Os animais do grupo II apresentaram alterações nos fígados, como congestão da veia centrolobular, balonamento hepatocelular, esteatose microgoticular, infiltrado leucocitário, vários núcleos picnóticos nos fígados, aumento no parênquima lobular e redução no parênquima não lobular, maior deposição de colágeno e redução de glicogênio. O tratamento com melatonina preveniu todas essas mudanças. Com isso, podemos concluir que a melatonina possui grande potencial terapêutico na prevenção de danos hepáticos em ratos adolescentes submetidas ao consumo moderado de álcool, além de efeitos positivos na deposição de colágeno e glicogênio no fígado.

Abstract (English)

The present study evaluated whether melatonin administered during adolescence can prevent the deleterious effects produced by alcohol on the liver. Thirty albino female rats (Rattus norvegicus albinus), 40 days old, virgins, weighing approximately 150±10g, from the Wistar lineage and were divided into the following groups: I – Adolescent rats that did not receive alcohol and euthanized at 60 days of life; II – Adolescent rats subjected to chronic alcohol consumption and euthanized at 60 days of life; III – Adolescent rats subjected to chronic alcohol consumption and simultaneously treated with melatonin, and euthanized at 60 days of life. The collected organs underwent histological processing and to obtain the results, morphometric, histopathological and histochemical analyzes were performed. Alcohol was administered by gavage. intragastric injection at a dosage of 3 g/Kg of ethyl alcohol in the rats of groups II and III for 20 days. Melatonin was administered in daily injections of 0.8 mg/Kg, always at the beginning of the night, intraperitoneally for 20 days. When analyzing the weight of the animals, no significant difference was observed between the groups. The animals in group II presented alterations in the livers such as congestion of the centrilobular vein, hepatocellular ballooning, microgoticular steatosis, leukocyte infiltrate, several pyknotic nuclei in the livers, increase in lobular parenchyma and reduction in non-lobular parenchyma, greater deposition of collagen and reduction of glycogen. Melatonin treatment prevented all these changes. With this, we can conclude that melatonin has great therapeutic potential in the prevention of liver damage in adolescent rats subjected to moderate alcohol consumption, in addition to positive effects on the deposition of collagen and glycogen in the liver.

Abstract (Spanish)

El presente estudio evaluó si la melatonina administrada durante la adolescencia puede prevenir los efectos perjudiciales producidos por el alcohol en el hígado. Se utilizaron treinta ratas albinas hembra (Rattus norvegicus albinus), de 40 días de edad, vírgenes, con un peso aproximado de 150±10g, de la línea Wistar, y se dividieron en los siguientes grupos: I – Ratas adolescentes que no recibieron alcohol y fueron sacrificadas a los 60 días de vida; II – Ratas adolescentes sometidas a consumo crónico de alcohol y sacrificadas a los 60 días de vida; III – Ratas adolescentes sometidas a consumo crónico de alcohol y tratadas simultáneamente con melatonina, y sacrificadas a los 60 días de vida. Los órganos recolectados fueron sometidos a procesamiento histológico y para obtener los resultados se realizaron análisis morfométricos, histopatológicos e histoquímicos. El alcohol se administró por gavage (sonda gástrica) en una dosis de 3 g/Kg de alcohol etílico en las ratas de los grupos II y III durante 20 días. La melatonina se administró en inyecciones diarias de 0,8 mg/Kg, siempre al inicio de la noche, por vía intraperitoneal durante 20 días. Al analizar el peso de los animales, no se observaron diferencias significativas entre los grupos. Los animales del grupo II presentaron alteraciones en los hígados, como congestión de la vena centrolobulillar, hepatocelular, microgoticular, infiltrado leucocitario, varios núcleos picnóticos en los hígados, aumento del parénquima lobulillar y reducción del parénquima no lobulillar, mayor deposición de colágeno y reducción de glucógeno. El tratamiento con melatonina previno todos estos cambios. Con esto, podemos concluir que la melatonina tiene un gran potencial terapéutico en la prevención del daño hepático en ratas adolescentes expuestas a un consumo moderado de alcohol, además de efectos positivos en la deposición de colágeno y glucógeno en el hígado.

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Additional details

Additional titles

Translated title (English)
Effect of melatonin on the liver histophysiology of adolescent rats exposed to alcohol
Translated title (Spanish)
Efecto de la melatonina en la histofisiología del hígado de ratas adolescentes expuestas al alcohol

References

  • ABD-ALLAH, A. R. A. et al. Effect of melatonin on estrogen and progesterone receptors in relation to uterine contractions in rats. Pharmacological Research , v . 47, pp. 349–354, 2003. DOI: 10.1016/s1043-6618(03)00014-8.
  • ALLAITHI, L. A. A.; Al-AZAWI, W. M. K. Study of the effect of salvia officinalis leaves extract and xenical drug on some of the biochemical and histological parameters in the rats induced with hyperlipidemia. Plant Archives, v . 19, pp. 1111–1122, 2019.
  • AMARAL, F. G. et al. New insights into the function of melatonin and its role in metabolic disturbances. Expert Review of Endocrinology & Metabolism, v. 14, no. 4, pp. 293–300, 2019. DOI: 10.1080/17446651.2019.1631158.
  • ANDRADE, A. G.; SIU, E. R. Alcohol and the health of Brazilians: panorama 2019. Health and alcohol information center. P. 104, 2019.
  • ARAÚJO-FILHO, J. L. S. et al. Histomorphometric analysis of the heart of rats indirectly exposed to ethanol and chronic malnutrition during the perinatal period. Journal of Medical and Biological Sciences, v. 6, no. 1, pp. 17-25, 2007. DOI: 10.9771/cmbio.v6i1.4144.
  • BEST, C. A.; LAPOSATA, M. Fatty acid ethyl esters toxic non-oxidative metabolites of ethanol and markers of ethanol intake. Frontiers in Bioscience, v. 8, no. 5, pp. e202-217, 2003. DOI: 10.2741/931.
  • BHADORIA, P. et al. Effect of Ethephon on the Liver in Albino Rats: A Histomorphometric Study. Biomedical Journal, v. 38, no. 5, pp. 421–427, 2015. DOI: 10.4103/2319-4170.155589.
  • BROCARDO, P. S.; GIL-MOHAPEL, J.; CHRISTIE, B. R. The role of oxidative stress in fetal alcohol spectrum disorders. brain Research Reviews, vol. 67, no. 1–2, pp. 209–225, 2011. DOI: 10.1016/j.brainresrev.2011.02.001.
  • ENGELMAN, M. F. B. et al. Morphometric study of the liver of rats submitted to supraphysiological doses of thyroxine. Brazilian Archives of Endocrinology & Metabolism, v. 45, no. 2, pp. 173-179, 2001. DOI: 10.1590/S0004-27302001000200009.
  • FARIA, V. S. et al. Melatonin Potentiates Exercise-Induced Increases in Skeletal Muscle PGC-1 α and Optimizes Glycogen Replenishment. Frontiers in Physiology, vol. 13, pp. 1–11, 2022. DOI: 10.3389/fphys.2022.803126.
  • FARKAS, Á.; KEMÉNY, L. Alcohol, Liver, Systemic Inflammation and Skin: A Focus on Patients with Psoriasis. Skin Pharmacology and Physiology, v. 26, no. 3, pp. 119–126, 2013. DOI: 10.1159/000348865.
  • FIOCRUZ. III national survey on drug use by the Brazilian population. [sl .: sn], 2017. Available at: <https: //www.arc a .fiocruz.br/bitstream/icict/34614/1/III%20LNUD_PORTUGU%C3%8 AS.pdf>.
  • GALANO, A.; TAN, D. X; REITER, R. J. Melatonin as a natural ally against oxidative stress: a physicochemical examination. Journal of Pineal Research, vol. 51, no. 1, pp. 1-16, 2011. DOI: 10.1111/j.1600-079X.2011.00916.x.
  • GALANO, A.; TAN, D. X.; REITER, R. J. Melatonin: A Versatile Protector against Oxidative DNA Damage. Molecules, v. 23, no. 3, pp. 530, 2018. DOI: 10.3390/molecules23030530.
  • GAO, B.; BATALLER, R. Alcoholic Liver Disease: Pathogenesis and New Therapeutic Targets. GASTROENTEROLOGY, v. 141, no. 5, pp. 1572-1585, 2011. DOI: 10.1053/j.gastro.2011.09.002.
  • GHOSH, P. et al. Insights into the antioxidative mechanisms of melatonin in ameliorating chromium-induced oxidative stress-mediated hepatic and renal tissue injuries in male Wistar rats. Food and Chemical Toxicology, v. 173, pp. 113630, 2023. DOI: 10.1016/j.fct.2023.113630.
  • GUNATA, M.; PARLAKPINAR, H.; ACET, H. A. Melatonin: A review of its potential functions and effects on neurological diseases. Revue Neurologique, vol. 176, no. 3, pp. 148–165, 2020. DOI: 10.1016/j.neurol.2019.07.025.
  • HARDELAND, R.; PANDI-PERUMAL, S. R.; CARDINALI, D. P. Melatonin. The International Journal of Biochemistry & Cell Biology, v. 38, no. 3, pp. 313-316, 2006. DOI: 10.1016/j.biocel.2005.08.020.
  • HU, C. et al. Protective role of melatonin in early-stage and end-stage liver cirrhosis. Journal of Cellular and Molecular Medicine, v. 23, no. 11, pp. 7151–7162, 2019. DOI: 10.1111/jcmm.14634.
  • HU, S. et al. Melatonin protects against alcoholic liver injury by attenuating oxidative stress, inflammatory response, and apoptosis. European Journal of Pharmacology, v. 616, pp. 287–292, 2009. DOI: 10.1016/j.ejphar.2009.06.044.
  • KISSELEVA, T.; BRENNER, D. A. The Crosstalk between Hepatocytes, Hepatic Macrophages, and Hepatic Stellate Cells Facilitates Alcoholic Liver Disease. Cell Metabolism, v. 30, no. 5, pp. 850-852, 2019. DOI: 10.1016/j.cmet.2019.10.010.
  • KLEINER, D. E. et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology, v. 41, no. 6, pp. 1313–1321, 2005. DOI: 10.1002/hep.20701.
  • KURCER, Z. et al. Melatonin improves methanol intoxication-induced oxidative liver injury in rats. Journal of Pineal Research, vol. 43, no. 1, pp. 42-49, 2007. DOI: 10.1111/j.1600-079X.2007.00441.x.
  • KURHALUK, N.; TKACHENKO, H. Melatonin and alcohol-related disorders. Chronobiology International, v. 37, no. 6, pp. 781–803, 2020. DOI:10.1080/07420528.2020.1761372.
  • KURHALUK, N.; TKACHENKO, H.; LUKASH, O. Melatonin modulates oxidative phosphorylation, hepatic and kidney autophagy-caused subclinical endotoxemia and acute ethanol-induced oxidative stress. Chronobiology International, v. 37, no. 12, pp. 1709–1724, 2020. DOI: 10.1080/07420528.2020.1830792.
  • LI, N. et al. Melatonin ameliorates renal fibroblast-myofibroblast transdifferentiation and renal fibrosis through miR-21-5p regulation. Journal of Cellular and Molecular Medicine, v. 24, no. 10, pp. 5615–5628, 2020. DOI: 10.1111/jcmm.15221.
  • MAHIEU, S. et al. Melatonin reduces oxidative damage induced by aluminum in rat kidney. Toxicology Letters, v. 190, no. 1, pp. 9-15, 2009. DOI: 10.1016/j.toxlet.2009.06.852.
  • MARCO, I. N. et al. Long-Term Effects of Intermittent Adolescent Alcohol Exposure in Male and Female Rats. Frontiers in Behavioral Neuroscience, v. 11, no. 233, pp. 1-13, 2017. DOI: 10.3389/fnbeh.2017.00233.
  • MARTIN, J. V. et al. Effects of dietary caffeine and alcohol on liver carbohydrate and fat metabolism in rats. Medical science monitor: international medical journal of experimental and clinical research, v. 10, no. 12, pp. BR455-BR461, 2004.
  • MASSEY, V. L.; ARTEEL, G. E. Acute Alcohol-Induced Liver Injury. Frontiers in Physiology, vol. 3 n. 193, pp. 1-8, 2012. DOI: 10.3389/fphys.2012.00193.
  • MINCIS, M. et al. Alcohol and the Liver. GED: Gastroenterology Endoscopy digestive, v. 30, no. 4, pp. 152-162, 2011.
  • MOSTAFA, M. et al. Fatty Liver Disease: A Practical Approach. Archives of Pathology & Laboratory Medicine, v. 144, no. 1, pp. 62–70, 2020. DOI: 10.5858/arpa.2019-0341-RA.
  • MOUSTAFA, A. M. et al. Effect of bromocriptine on uterine contractility in near term pregnant rats. Pharmacological Research, v. 39, no. 2, p. 89-95, 1999. DOI: 10.1006/phrs.1998.0399.
  • NANJI, A. A.; FOGT, F.; GRINIUVIENE, B. Alterations in Glucose Transporter Proteins in Alcoholic Liver Disease in the Rat. The American Journal of Pathology, v. 146, no. 2, pp. 329-334, 1995.
  • NORBERG, A. et al. Role of Variability in Explaining Ethanol Pharmacokinetics: Research and Forensic Applications. Clinical Pharmacokinetics, v. 42, no. 1, p. 1–31, 2003. DOI: 10.2165/00003088-200342010-00001.
  • NWOZO, S.; AJAGBE, A.; OYINLOYE, B. Hepatoprotective effect of Piper guineense aqueous extract against ethanol-induced toxicity in male rats. Journal of Experimental and Integrative Medicine, v. 2, no. 1, pp. 71-76, 2012. DOI: 10.5455/jeim.241111.or.016.
  • PAGET, G. E.; BARNE, J. M. Evaluation of results: quantitative application in different species. Pharmacometrics , vol. 1. p. 161. 9th ed. New York: Academic Press; 1994.
  • POEGGELER, B. et al. Melatonin, hydroxyl radical- mediated oxidative damage, and aging: A hypothesis. Journal of Pineal Research, v. 14, no. 4, pp. 151–168, 1993. DOI: 10.1111/j.1600-079x.1993.tb00498.x.
  • RADIC, I. et al. Protective effects of whey on rat liver damage induced by chronic alcohol intake. Human & Experimental Toxicology, v . 38, no. 6, pp. 632–645, 2019. DOI: 10.1177/0960327119829518.
  • RADIC, I. et al. Protective effects of pumpkin (Cucurbita pepo L.) seed oil on rat liver damage induced by chronic alcohol consumption. Archives of Biological Sciences, vol. 73, no. 1, pp. 123–133, 2021. DOI: 10.2298/ABS201205008R.
  • RAMAIAH, S. K.; JAESCHKE, H. Hepatic neutrophil infiltration in the pathogenesis of alcohol-induced liver injury. Toxicology Mechanisms and Methods, v.17, n. 7, pp. 431– 440, 2007. DOI: 10.1080/00952990701407702.
  • REITER, R. J. et al. Peripheral Reproductive Organ Health and Melatonin: Ready for Prime Time", International Journal of Molecular Sciences, v. 14, no. 4, pp. 7231-7272, 2013. DOI: 10.3390/ijms14047231.
  • REITER, R. J.; TAN, D. X.; GALANO, A. Melatonin: exceeding expectations. Physiology (Bethesda, Md.), v. 29, no. 5, pp. 325–333, 2014. DOI: 10.1152/physiol.00011.2014.
  • ROCCO, A. et al. Alcoholic disease: Liver and beyond. World Journal of Gastroenterology, v. 20, no. 40, pp. 14652-14659, 2014. DOI: 10.3748/wjg.v20.i40.14652.
  • ROY S. et al. The role of miRNAs in the regulation of inflammatory processes during hepatofibrogenesis. Hepatobiliary Surgery and Nutrition, v. 4, no. 1, p. 24-33, 2015. DOI: 10.3978/j.issn.2304-3881.2015.01.05.
  • SCHEIDT, L. et al. Ethanol during adolescence decreased the BDNF levels in the hippocampus in adult male Wistar rats, but did not alter aggressive and anxiety -like behaviors. Trends Psychiatry Psychother. v. 7, no. 3, p. 143-151, 2015. DOI: 10.1590/2237-6089-2015-0017.
  • SCHILD, M. H.; GUY, C. D. Nonalcoholic Steatohepatitis. Surgical Pathology Clinics, v. 11, no. 2, pp. 267–285, 2018. DOI: 10.1016/j.path.2018.02.013.
  • SHIEH, J. M. et al. Melatonin ameliorates high fat diet-induced diabetes and stimulates glycogen synthesis via a PKC ζ -Akt-GSK3 β pathway in hepatic cells. Journal of Pineal Research, v. 47, no. 4, pp. 339–344, 2009. DOI: 10.1111/j.1600-079X.2009.00720.x.
  • SINGH, M., JADHAV, H. R. Melatonin: functions and ligands. Drug Discovery Today, v. 19, no. 9, pp. 1410-1418, 2014. DOI: 10.1016/j.drudis.2014.04.014.
  • SRINIVASAN, M. P.; SHAWKY, N. M.; KAPHALIA, B. S. Alcohol-induced ketonemia is associated with lowering of blood glucose, downregulation of gluconeogenic genes, and depletion of hepatic glycogen in type 2 diabetic db/db mice. Biochemical Pharmacology, v. 160, pp. 46-61, 2019. DOI: 10.1016/j.bcp.2018.12.005.
  • STEINER, J. L.; CROWELL, K. T.; LANG, C. H. Impact of Alcohol on Glycemic Control and Insulin Action. Biomoleculas, v. 5, no. 4, pp. 2223-2246, 2015. DOI: 10.3390/biom5042223.
  • TAO, Z. et al. Echinacoside ameliorates alcohol-induced oxidative stress and hepatic steatosis by affecting SREBP1c/FASN pathway via PPAR α. Food and Chemical Toxicology, v.148, pp. 1-9, 2021. DOI: 10.1016/j.fct.2020.111956.
  • ULLAH, U. et al. Hepatoprotective effects of melatonin and celecoxib against ethanol-induced hepatotoxicity in rats. Immunopharmacology and Immunotoxicology, v. 42, no. 3, pp. 255–263, 2020. DOI: 10.1080/08923973.2020.1746802.
  • VARLINSKAYA, E. I.; SPEAR, L. P.; SPEAR, N. E. Acute effects of ethanol on behavior of adolescent rats: Role of social context. Alcohol Clinical & Experimental Research, v. 25, no. 3, pp. 377–385, 2001. DOI: 10.1111/j.1530- 0277.2001.tb 02224.x.
  • VONGHIA, L. et al. Acute alcohol intoxication. European Journal of Internal Medicine, v. 19, no. 8, pp. 561–567, 2008. DOI: 10.1016/j.ejim.2007.06.033.
  • WHO – World Health Organization. Global status report on alcohol and health 2018. 2018, p. 472.
  • YANG, L. et al. Chronic Alcohol Exposure Increases Circulating Bioactive Oxidized Phospholipids. Journal of Biological Chemistry, v. 285, no. 29, pp. 22211–22220, 2010. DOI: 10.1074/jbc.M110.119982.
  • YEH, M. M.; BRUNT, E. M. Pathological features of fatty liver disease. Gastroenterology, v. 147, no. 4, pp. 754–764, 2014. DOI: 10.1053/j.gastro.2014.07.056.
  • ZHANG, H. et al. Melatonin ameliorates ochratoxin A induced liver inflammation, oxidative stress and mitophagy in mice involving in intestinal microbiota and restoring the intestinal barrier function. Journal of Hazardous Materials, v. 407, pp. 1-49, 2021. DOI: 10.1016/j.jhazmat.2020.124489.