Histological Interfaces of Liver, Kidney and Cerebrum in Male Rats exposed to Fluoxetine

Keywords: fluoxetine, depression, liver, kidney, cerebrum.



Fluoxetine is an antidepressant of selective serotonin reuptake inhibitor drug. It is used in treatment of depression, panic and anxiety. Also, it may decrease the risk of suicide in those over the age of sixty-five years. The current study was planned to investigate the histological effect of oral administration of fluoxetine (10 mg/kg body weight/day) on liver, kidney and cerebrum of male rats. Rats were divided randomly and equally into two groups; control group (n=8) and fluoxetine-treated group (n=8). After one month of administration; liver, kidney and cerebrum tissues would be taken to make histological slides. Histological alterations were observed in liver such as presence of few dead hepatocytes, congested blood vessels and inflammatory cells. Kidney also showed histological changes; in the cortex region include shrunken glomeruli tuft, hemorrhage and degenerated cells while in the medullary region included thickened wall of tubules and some of the epithelial tubule cells were degenerated. Alterations in the cerebrum were the presence of dead neuronal cells in the second and third layers of grey matter were due to fluoxetine. In conclusion, fluoxetine had a minute effect on the histological structure of liver, kidney and cerebrum tissues.



ANDERSON, I. M. 2000. Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability. J Affect Disord, 58, 19-36.
BANCROFT, J. D., STEVENS, A. & DAWSON, I. M. S. 1977. Theory and Practices of Histological Techniques. Edinburg, London, New York. ChurchillLivingstone.
BARDIN, L. 2011. The complex role of serotonin and 5-HT receptors in chronic pain. Behav Pharmacol, 22, 390-404.
BIROS, M. H., HICK, K., CEN, Y. Y., MANN, J., GAETZ, A., HANSEN, R. & SCHIMING, R. 2008. Occult depressive symptoms in adolescent emergency department patients. Arch Pediatr Adolesc Med, 162, 769-73.
CHEN, M. F., HUANG, Y. C., LONG, C., YANG, H. I., LEE, H. C., CHEN, P. Y., HOFFER, B. J. & LEE, T. J. 2012. Bimodal effects of fluoxetine on cerebral nitrergic neurogenic vasodilation in porcine large cerebral arteries. Neuropharmacology, 62, 1651-8.
CIPRIANI, A., BRAMBILLA, P., FURUKAWA, T., GEDDES, J., GREGIS, M., HOTOPF, M., MALVINI, L. & BARBUI, C. 2005. Fluoxetine versus other types of pharmacotherapy for depression. Cochrane Database Syst Rev, Cd004185.
DEAK, F., LASZTOCZI, B., PACHER, P., PETHEO, G. L., VALERIA, K. & SPAT, A. 2000. Inhibition of voltage-gated calcium channels by fluoxetine in rat hippocampal pyramidal cells. Neuropharmacology, 39, 1029-36.
INKIELEWICZ-STEPNIAK, I. 2011. Impact of fluoxetine on liver damage in rats. Pharmacol Rep, 63, 441-7.
JANG, C. H., JOO, M. C., NOH, S. E., LEE, S. Y., LEE, D. B., LEE, S. H., KIM, H. K. & PARK, H. I. 2016. Effects of Hippotherapy on Psychosocial Aspects in Children With Cerebral Palsy and Their Caregivers: A Pilot Study. Ann Rehabil Med, 40, 230-6.
JOHNSTONE, T., VAN REEKUM, C. M., URRY, H. L., KALIN, N. H. & DAVIDSON, R. J. 2007. Failure to regulate: counterproductive recruitment of top-down prefrontal-subcortical circuitry in major depression. J Neurosci, 27, 8877-84.
MATSUMOTO, K., PUIA, G., DONG, E. & PINNA, G. 2007. GABA(A) receptor neurotransmission dysfunction in a mouse model of social isolation-induced stress: possible insights into a non-serotonergic mechanism of action of SSRIs in mood and anxiety disorders. Stress, 10, 3-12.
MOYSES, Z. P., NAKANDAKARI, F. K. & MAGALDI, A. J. 2008. Fluoxetine effect on kidney water reabsorption. Nephrol Dial Transplant, 23, 1173-8.
ÖZDEN, H., BILDIRICI, K. ı., ÜSTÜNER, D., ÜSTÜNER, C., CENGIZ, B. P., TÜLAY, A. & YıLMAZ, V. 2005. Histopathologic examination of rat liver after experimental application of fluoxetine. Türkiye Ekopatoloji Dergisi, 11, 9-15.
TEN HOLT, W. L., VAN IPEREN, C. E., SCHRIJVER, G. & BARTELINK, A. K. 1996. Severe hyponatremia during therapy with fluoxetine. Arch Intern Med, 156, 681-2.
TIRADENTES, R. V., PIRES, J. G., SILVA, N. F., RAMAGE, A. G., SANTUZZI, C. H. & FUTURO NETO, H. A. 2014. Effects of acute administration of selective serotonin reuptake inhibitors on sympathetic nerve activity. Braz J Med Biol Res, 47, 554-9.
UNGVARI, Z., PACHER, P. & KOLLER, A. 2000. Serotonin reuptake inhibitor fluoxetine decreases arteriolar myogenic tone by reducing smooth muscle [Ca2+]i. J Cardiovasc Pharmacol, 35, 849-54.
WERNICKE, J. F. 2004. Safety and side effect profile of fluoxetine. Expert Opin Drug Saf, 3, 495-504.
YILMAZ, A., ELBEY, B., YAZGAN, U. C., DONDER, A., ARSLAN, N., ARSLAN, S., ALABALIK, U. & ASLANHAN, H. 2016. Protective Effects of Caffeic Acid Phenethyl Ester on Fluoxetine-Induced Hepatotoxicity: An Experimental Study. Biomed Res Int, 2016, 1247191.
How to Cite
“Histological Interfaces of Liver, Kidney and Cerebrum in Male Rats exposed to Fluoxetine” (2016) Zanco Journal of Pure and Applied Sciences, 28(5), pp. 126-135. doi: 10.21271/zjpas.v28i5.725.