Effects of excitatory and inhibitory of nitric oxide on Kupffer cells and volume of sinusoids in rat liver
Subject Areas : Journal of Animal Biology
Mohammad Talvari
1
,
Atarodsadat Mostafavinia
2
,
Parivash Davoudi
3
,
Mobina Zargar
4
,
Seyed Mohammmad Hossein Noori Mougahi
5
1 - Department of Anatomical Sciences & Cognitive Neuroscience, TMS.C., Islamic Azad University, Tehran, Iran.
2 - Department of Anatomy, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
3 - Anatomy department- medical sciences branch- Islamic Azad university- Tehran- Iran
4 - Department of Anatomical Sciences & Cognitive Neuroscience, TMS.C., Islamic Azad University, Tehran, Iran.
5 - Department of Anatomy, Faculty of Medicine, Ahwaz Campus, Islamic Azad University, Ahwaz, Iran.
Keywords: Liver, Kupffer cell, Sinusoid, Nitric Oxide, L-Arginine, L-NAME,
Abstract :
Nitric oxide (NO) is a diatomic and lipophilic molecule that is produced by the nitric oxide synthase (Nos) from L-Arginine in many organs of the body. Considering the important roles of nitric oxide in many physiological processes of the body and limited number of researches that have been done in the field of its effects on Kupffer cells and volume of sinusoids, the purpose of this study is to evaluate excitatory and inhibitory effects of Nitric Oxide on liver histology in rat. Forty female Wistar rats with average weight of 200-250 gr after pregnancy were randomly divided into 5 groups. Except the control group, the rest of the groups intraperitoneally received Normal Saline, L-Arginine, L-NAME and mixture of L-NAME and L-Arginine respectively with the same dose in the 3th, 4th and 5th days of pregnancy. Then, in 18th day of pregnancy, Rats were anesthetized and we took out the animal’s liver and examined Kupffer cells and volume of sinusoids with Hematoxylin-Eosin staining. In this study, Kupffer cells and volume of sinusoids were significantly different in L-NAME and L-Arginine groups with control group, whereas in L-NAME+Arginine group no significant difference was observed with the control group. This study showed that the combined use of L-Arginine and L-NAME can modulate the excitatory and inhibitory effects of nitric oxide on the rat liver.
1. Abdel-Salam, O. M. E., Youness, E. R., Mohammed, N. A., Yassen, N. N., Khadrawy, Y. A., El-Toukhy, S. E., & Sleem, A. A. (2017). Nitric oxide synthase inhibitors protect against brain and liver damage caused by acute malathion intoxication. Asian Pac J Trop Med, 10(8), 773-786. https://doi.org/10.1016/j.apjtm.2017.07.018 2. Abu-Amara, M., Yang, S. Y., Seifalian, A., Davidson, B., & Fuller, B. (2012). The nitric oxide pathway--evidence and mechanisms for protection against liver ischaemia reperfusion injury. Liver Int, 32(4), 531-543. https://doi.org/10.1111/j.1478-3231.2012.02755.x 3. Arikawe, A. P., Udenze, I. C., Olusanya, A. W., Akinnibosun, O. A., Dike, I., & Duru, B. N. (2019). L-arginine supplementation lowers blood pressure, protein excretion and plasma lipid profile in experimental salt-induced hypertension in pregnancy: Relevance to preeclampsia. Pathophysiology, 26(3-4), 191-197. https://doi.org/10.1016/j.pathophys.2019.02.002 4. Azargoonjahromi, A. (2023). Dual role of nitric oxide in Alzheimer's disease. Nitric Oxide, 134-135, 23-37. https://doi.org/10.1016/j.niox.2023.03.003 5. Barrett, K. E., Barman, S. M., Brooks, H. L., & Yuan, J. X. J. (2019). In Ganong's Review of Medical Physiology, 26e. McGraw-Hill Education. accessmedicine.mhmedical.com/content.aspx?aid=1158993487 6. Billiar, T. R., Curran, R. D., Ferrari, F. K., Williams, D. L., & Simmons, R. L. (1990). Kupffer cell:hepatocyte cocultures release nitric oxide in response to bacterial endotoxin. J Surg Res, 48(4), 349-353. https://doi.org/10.101-0022-/6-90073(90) 4804/6b 7. Billiar, T. R., Curran, R. D., Stuehr, D. J., Stadler, J., Simmons, R. L., & Murray, S. A. (1990). Inducible cytosolic enzyme activity for the production of nitrogen oxides from L-Arginine in hepatocytes. Biochem Biophys Res Commun,1034-1040,(3).168 https://doi.org/10.1016/0006-291x(90)91133-d 8. Boje, K. M. (2004). Nitric oxide neurotoxicity in neurodegenerative diseases. Front Biosci, 9, 763-776. https://doi.org/10.2741/1268 9. Bordbar, H., Soleymani, F., Nadimi, E., Yahyavi, S. S., & Fazelian-Dehkordi, K. (2021). A Quantitative Study on the Protective Effects of Resveratrol against Bisphenol A-induced Hepatotoxicity in Rats: A Stereological Study. Iran J Med Sci, 46(3), 218-227. https://doi.org/10.30476/ijms.2020.83308.1233 10. Chou, T. C., Yen, M. H., Li, C. Y., & Ding, Y. A. (1998). Alterations of nitric oxide synthase expression with aging and hypertension in rats. Hypertension, 31(2), 643-648. https://doi.org/10.1161/01.hyp.31.2.643 11. Choudhari, S. K., Chaudhary, M., Bagde, S., Gadbail, A. R., & Joshi, V. (2013). Nitric oxide and cancer: a review. World J Surg Oncol, 11, 118. https://doi.org/10.1186/1477-7819-11-118 12. Cogger, V. C., Muller, M., Fraser, R., McLean, A. J., Khan, J., & Le Couteur, D. G. (2004). The effects of oxidative stress on the liver sieve. J Hepatol, 41(3), 370-376. https://doi.org/10.1016/j.jhep.2004.04.034 13. Cottart, C. H., Do, L., Blanc, M. C., Vaubourdolle, M., Descamps, G., Durand, D., Galen, F. X., & Clot, J. P. (1999). Hepatoprotective effect of endogenous nitric oxide during ischemia-reperfusion in the rat. Hepatology, 29(3), 809-813.
https://doi.org/10.1002/hep.510290317 14. Goodarzi, N., Zangeneh, M. M., Zangeneh, A., Najafi, F., & Tahvilian, R. (2017). Protective Effects of Ethanolic Extract of Allium Saralicum R.M. Fritsch on CCl4- Induced Hepatotoxicity in Mice [Applicable]. Journal of Rafsanjan University of
Medical Sciences, 16(3), 227-238. http://journal.rums.ac.ir/article-1-3706-en.html 15. Guix, F. X., Uribesalgo, I., Coma, M., & Muñoz, F. J. (2005). The physiology and pathophysiology of nitric oxide in the
brain. Prog Neurobiol, 76(2), 126-152. https://doi.org/10.1016/j.pneurobio.2005.06.001 16. Harlan, R. E., Webber, D. S., & Garcia, M. M. (2001). Involvement of nitric oxide in morphine-induced c-Fos
expression in the rat striatum. Brain Res Bull, 54(2), 207-212. https://doi.org/10.1016/s0361-9230(00)00451-2 17. Hsu, C. M., Wang, J. S., Liu, C. H., & Chen, L. W. (2002). Kupffer cells protect liver from ischemia-reperfusion injury by an inducible nitric oxide synthase-dependent mechanism. Shock, 17(4), 280-285. https://doi.org/10.1097/00024382-
200204000-00007 18. Ikeda, U., Maeda, Y., & Shimada, K. (1998). Inducible nitric oxide synthase and atherosclerosis. Clin Cardiol, 21(7),
473-476. https://doi.org/10.1002/clc.4960210705 19. Ischiropoulos, H., & Beckman, J. S. (2003). Oxidative stress and nitration in neurodegeneration: cause, effect, or
association? J Clin Invest, 111(2), 163-169. https://doi.org/10.1172/JCI17638 20. Isobe, M., Katsuramaki, T., Hirata, K., Kimura, H., Nagayama, M., & Matsuno, T. (1999). Beneficial effects of inducible nitric oxide synthase inhibitor on reperfusion injury in the pig liver. Transplantation, 68(6), 803-813.
https://doi.org/10.1097/00007890-199909270-00013 21. Iwakiri, Y., & Kim, M. Y. (2015). Nitric oxide in liver diseases. Trends Pharmacol Sci, 36(8), 524-536.
https://doi.org/10.1016/j.tips.2015.05.001 22. Iwasaki, J., Afify, M., Bleilevens, C., Klinge, U., Weiskirchen, R., Steitz, J., Vogt, M., Yagi, S., Nagai, K., Uemoto, S., & Tolba, R. H. (2019). The Impact of a Nitric Oxide Synthase Inhibitor (L-NAME) on Ischemia⁻Reperfusion Injury of Cholestatic Livers by Pringle Maneuver and Liver Resection after Bile Duct Ligation in Rats. Int J Mol Sci, 20(9).
https://doi.org/10.3390/ijms 200 92114. 23.
Joseph Loscalzo, L. J. (2022). Harrison's Internal Medicine, 21th Edition Vol 1 & Vol 2. 24. Kawahara, K., Hachiro, T., Yokokawa, T., Nakajima, T., Yamauchi, Y., & Nakayama, Y. (2006). Ischemia/reperfusion-induced death of cardiac myocytes: possible involvement of nitric oxide in the coordination of ATP supply and demand
during ischemia. J Mol Cell Cardiol, 40(1), 35-46. https://doi.org/10.1016/j.yjmcc.2005.06.020 25. Kibbe, M., Billiar, T., & Tzeng, E. (1999). Inducible nitric oxide synthase and vascular injury. Cardiovasc Res, 43(3),
650-657. https://doi.org/10.1016/s0008-6363(99)00130-3 26. Knowles, R. G., Merrett, M., Salter, M., & Moncada, S. (1990). Differential induction of brain, lung and liver nitric
oxide synthase by endotoxin in the rat. Biochem J, 270(3), 833-8. 36. https://doi.org/10.1042/bj2700833 27. Kotsiou, O. S., Gourgoulianis, K. I., & Zarogiannis, S. G. (2021). The role of nitric oxide in pleural disease. Respir Med,
179, 106350. https://doi.org/10.1016/j.rmed.2021.106350 28. Margaritis, E. V., Yanni, A. E., Agrogiannis, G., Liarakos, N., Pantopoulou, A., Vlachos, I., Papachristodoulou, A., Korkolopoulou, P., Patsouris, E., Kostakis, M., Perrea, D. N., & Kostakis, A. (2011). Effects of oral administration of (L)-arginine, (L)-NAME and allopurinol on intestinal ischemia/reperfusion injury in rats. Life Sci, 88(23-24), 1070-1076.
https://doi.org/10.1016/j.lfs.2011.04.009 29. Mescher, A. L. (2024). Editor. In Junqueira's Basic Histology: Text and Atlas, 17th Edition (pp. 339-340). McGraw Hill.
ccessmedicine.mhmedical.com/content.aspx?aid=1203450994 30. Moncada, S., Palmer, R. M., & Higgs, E. A. (1989). Biosynthesis of nitric oxide from L-arginine. A pathway for the regulation of cell function and communication. Biochem Pharmacol, 38(11), 1709-1715. https://doi.org/10.1016/0006-
2952(89)90403-6 31. Mondillo, C., Pagotto, R. M., Piotrkowski, B., Reche, C. G., Patrignani, Z. J., Cymeryng, C. B., & Pignataro, O. P. (2009). Involvement of nitric oxide synthase in the mechanism of histamine-induced inhibition of Leydig cell steroidogenesis via histamine receptor subtypes in Sprague-Dawley rats. Biol Reprod, 80(1), 144-152.
https://doi.org/10.1095/biolreprod.108.069484 32. Noori mugahi, SMH., S. Z., Movaseghi Sh, Mostafavi Nia A. (2021). Investigation of excitatory and inhibitory effects
of L-Arginine and L-NAME on thickness of the cortex and medulla of thymus in pregnant rats. [In Persian]. 33. Noori mugahi, SMH., Mostafavinia, A. M., Davodi, P., Sadr, M, S., Shrefi, Z. (2021). Stereological Study of Number of Follicles and Mean Follicular Diameters of Spleen Following L-NAME Administration in Pregnant Rat. Medical council of
I.R.I. [In Persian] 34. Ohmori, H., Dhar, D. K., Nakashima, Y., Hashimoto, M., Masumura, S., & Nagasue, N. (1998). Beneficial effects of FK409, a novel nitric oxide donor, on reperfusion injury of rat liver. Transplantation, 66(5), 579-585.
https://doi.org/10.1097/00007890-199809150-00005 35. Pfeiffer, S., Leopold, E., Schmidt, K., Brunner, F., & Mayer, B. (1996). Inhibition of nitric oxide synthesis by NG-nitro-L-arginine methyl ester (L-NAME): requirement for bioactivation to the free acid, NG-nitro-L-arginine. Br J Pharmacol,
118(6), 1433-1440. https://doi.org/10.1111/j.1476-5381.1996.tb15557.x 36. Razavi, H. M., Hamilton, J. A., & Feng, Q. (2005). Modulation of apoptosis by nitric oxide: implications in myocardial
ischemia and heart failure. Pharmacol Ther, 106(2), 147-162. https://doi.org/10.1016/j.pharmthera.2004.11.006 37. Reyes, A. A., Karl, I. E., & Klahr, S. (1994). Role of arginine in health and in renal disease. Am J Physiol, 267(3 Pt 2),
F331-346. https://doi.org/10.1152/ajprenal.1994.267.3.F331 38. Rochette, L., Lorin, J., Zeller, M., Guilland, J. C., Lorgis, L., Cottin, Y., & Vergely, C. (2013). Nitric oxide synthase inhibition and oxidative stress in cardiovascular diseases: possible therapeutic targets? Pharmacol Ther, 140(3), 239-257. https://doi.org/10.1016/j.pharmthera.2013.07.004
39. Shimamura, T., Zhu, Y., Zhang, S., Jin, M. B., Ishizaki, N., Urakami, A., Totsuka, E., Kishida, A., Lee, R., Subbotin, V., Furukawa, H., Starzl, T. E., & Todo, S. (1999). Protective role of nitric oxide in ischemia and reperfusion injury of the liver.
J Am Coll Surg, 188(1), 43-52. https://doi.org/10.1016/s1072-7515(98)00259-2 40. Sikiric, P., Seiwerth, S., Grabarevic, Z., Rucman, R., Petek, M., Jagic, V., Turkovic, B., Rotkvic, I., Mise, S., Zoricic, I., Konjevoda, P., Perovic, D., Jurina, L., Separovic, J., Hanzevacki, M., Artukovic, B., Bratulic, M., Tisljar, M., Gjurasin, M.,. Marovic, A. (1997). The influence of a novel pentadecapeptide, BPC 157, on N(G)-nitro-L-arginine methylester and L-arginine effects on stomach mucosa integrity and blood pressure. Eur J Pharmacol, 332(1), 23-33.
https://doi.org/10.1016/s0014-2999(97)01033-9 41. Southan, G. J., & Szabó, C. (19. (96 .Selective pharmacological inhibition of distinct nitric oxide synthase isoforms.
Biochem Pharmacol, 51(4), 383-394. https://doi.org/10.1016/0006-2952(95)02099-3 42. Taha, M. O., Caricati-Neto, A., Ferreira, R. M., Simões Mde, J., Monteiro, H. P., & Fagundes, D. J. (2012). L-arginine in the ischemic phase protects against liver ischemia-reperfusion injury. Acta Cir Bras, 27(9), 616-623.
https://doi.org/10.1590/s0102-86502012000900005 43. Taylor, B. S., Alarcon, L. H., & Billiar, T. R. (1998). Inducible nitric oxide synthase in the liver: regulation and function.
Biochemistry (Mosc), 63(7), 766-781. https://www.ncbi.nlm.nih.gov/pubmed/9721329 44. Zhang, B., Liu, Q. H., Zhou, C. J., Hu, M. Z., & Qian, H. X. (2016). Protective effect of eNOS overexpression against ischemia/reperfusion injury in small-for-size liver transplantation. Exp Ther Med, 12(5), 3181-3188.
https://doi.org/10.3892/etm.2016.3762