Hepato-defensive effect of Cysteine, Ursodeoxycholic acid and Silymarin on histopathological and some biochemical parameters of Wister albino rat intoxicated by CCl4
Keywords:L-Cysteine, Ursoflor, hepatotoxicity, carbon tetrachloride, Silybum marianum
The liver is an essential organ in the body for detoxification drugs and toxic substances. The present study was designed to investigate the hepatoprotective effects of L-Cysteine, Ursodeoxycholic acid (Ursoflor), and Silymarin against carbon tetrachloride-induced liver injury in rats. Twenty adult male rats were used in this work; they were randomly divided into five groups (4 rats/group). The first group served as the control group and received 0.5 ml of normal saline orally daily; the second group injected intraperitoneally with CCl4 (1.5 ml/kg B.W. twice a week), the third group were treated orally with the silymarin at dose of (200 mg/kg B.W. in normal saline orally + CCl4 daily, the fourth group was treated with Ursoflor drug at dose of (50 mg/kg B.W. in 0.5 normal saline orally+CCl4 daily. While the fifth group was treated with cysteine at dose of (50mg/kg B.W. in normal saline by oral gavage) +CCl4. at the end of this study, the biochemical assessment showed alterations in enzyme activity which indicates the hepatocyte injury due to CCl4 toxicity, The production of ROS indicated by elevated levels in MDA and Peroxynitrite was noticed, which improved partially by the antioxidant effect of L- Cysteine, Ursodeoxycholic acid, and Silymarin, these results further backed by histological examination of the liver showed that CCl4 caused severe injury to the liver including a high number of fat droplets deposition in the cytoplasm of the hepatocyte, clear vascularization appeared and disorganization of the liver cells were determined, on the other hand, Silymarin has showed good protection against these injurious effects of CCl4.
ABDEL-SALAM, O.M., SLEEM, A.A. and SHAFFIE, N.M. (2010) Effect of Viscum album on acute hepatic damage caused by carbon tetrachloride in rats. Turkish Journal of Medical Sciences, 40,(3), 421-426.
ABDEL SALAM, O., HASSAN ORABY, F. and HASSAN, N. (2007) Vinpocetine ameliorates acute hepatic damage caused by administration of carbon tetrachloride in rats. Acta Biologica Hungarica, 58,(4), 411-419.
ABENAVOLI, L., IZZO, A.A., MILIĆ, N., CICALA, C., SANTINI, A. and CAPASSO, R. (2018) Milk thistle (Silybum marianum): A concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases. Phytotherapy Research, 32,(11), 2202-2213.
AHMED, H.S., MOHAMED, W.R., MOAWAD, A.S., OWIS, A.I., AHMED, R.R. and ABOUZID, S.F. (2020) Cytotoxic, hepatoprotective and antioxidant activities of Silybum marianum variety albiflorum growing in Egypt. Natural product research, 34,(24), 3540-3544.
AL-SALMI, F.A., AL-EISA, R., HAMZA, R.Z., KHALED, H.E. and EL-SHENAWY, N.S. (2019) Protective Effect of L-cysteine Against Sodium Valproate-induced Oxidant Injury in Testis of Rats. International Journal of Pharmacology, 15,(2), 248-256.
AL AMIN, A. and MENEZES, R.G. (2020) Carbon tetrachloride toxicity. StatPearls [Internet].
BAHMANI, M., SHIRZAD, H., RAFIEIAN, S. and RAFIEIAN-KOPAEI, M. (2015) Silybum marianum: beyond hepatoprotection. Journal of evidence-based complementary & alternative medicine, 20,(4), 292-301.
BECKMAN, J.S., ISCHIROPOULOS, H., ZHU, L., VAN DER WOERD, M., SMITH, C., CHEN, J., HARRISON, J., MARTIN, J.C. and TSAI, M. (1992) Kinetics of superoxide dismutase-and iron-catalyzed nitration of phenolics by peroxynitrite. Archives of biochemistry and biophysics, 298,(2), 438-445.
BOUHALIT, S. and KECHRID, P.Z. (2018) Protective role of L-cysteine against nickel induced hepatotoxicity in Albino Wistar rats. J Pharmacol, 2,(3), 33.
BUEGE, J. and AUST, S. (1978) Microsomal lipid peroxidation methods enzymol 52: 302–310. Find this article online.
CORCHETE, P. (2008) Silybum marianum (L.) Gaertn: the source of silymarin. Bioactive molecules and medicinal plants. Springer.
DEMIROREN, K., DOGAN, Y., KOCAMAZ, H., OZERCAN, I.H., ILHAN, S., USTUNDAG, B. and BAHCECIOGLU, I.H. (2014) Protective effects of L-carnitine, N-acetylcysteine and genistein in an experimental model of liver fibrosis. Clinics and research in hepatology and gastroenterology, 38,(1), 63-72.
EMINZADE, S., URAS, F. and IZZETTIN, F.V. (2008) Silymarin protects liver against toxic effects of anti-tuberculosis drugs in experimental animals. Nutrition & Metabolism, 5,(1), 1-8.
FANOUDI, S., ALAVI, M.S., KARIMI, G. and HOSSEINZADEH, H. (2020) Milk thistle (Silybum Marianum) as an antidote or a protective agent against natural or chemical toxicities: a review. Drug and chemical toxicology, 43,(3), 240-254.
FATMA, N. and UPHADHYAY, R. (2015) Euphorbia nivulia Buch. Ham.: A boon for jaundice (A case study). Annals of Plant Sciences, 4,(6), 1137-1139.
FENG, M., WANG, Q., WANG, H. and GUAN, W. (2013) Tumor necrosis factor-alpha preconditioning attenuates liver ischemia/reperfusion injury through preserving sarco/endoplasmic reticulum calcium-ATPase function. journal of surgical research, 184,(2), 1109-1113.
FRIEDMAN, S.L. Published. Cytokines and fibrogenesis. Seminars in liver disease, 1999. © 1999 by Thieme Medical Publishers, Inc., 129-140.
GAZAK, R., WALTEROVA, D. and KREN, V. (2007) Silybin and silymarin-new and emerging applications in medicine. Current medicinal chemistry, 14,(3), 315-338.
GOULD, R.L. and PAZDRO, R. (2019) Impact of supplementary amino acids, micronutrients, and overall diet on glutathione homeostasis. Nutrients, 11,(5), 1056.
GUO, M., ZHAO, J., ZHAI, Y., ZANG, P., LV, Q. and SHANG, D. (2019) A prospective study of hepatic safety of statins used in very elderly patients. BMC geriatrics, 19,(1), 352.
HERMENEAN, A., STAN, M., ARDELEAN, A., PILAT, L., MIHALI, C.V., POPESCU, C., NAGY, L., DEÁK, G., ZSUGA, M. and KÉKI, S. (2015) Antioxidant and hepatoprotective activity of milk thistle (Silybum marianum L. Gaertn.) seed oil. Open life sciences, 1,(open-issue).
IŞıK, S., KARAMAN, M., MICILI, S.Ç., ÇAĞLAYAN-SÖZMEN, Ş., BAĞRıYANıK, H.A., ARıKAN-AYYıLDıZ, Z., UZUNER, N. and KARAMAN, Ö. (2017) Beneficial effects of ursodeoxycholic acid via inhibition of airway remodelling, apoptosis of airway epithelial cells, and Th2 immune response in murine model of chronic asthma. Allergologia et Immunopathologia, 45,(4), 339-349.
KABIRI, N., AHANGAR-DARABI, M., SETORKI, M. and RAFIEIAN-KOPAEI, M. (2013) The effect of silymarin on liver injury induced by Thioacetamide in rats. Journal of HerbMed Pharmacology, 2,(2), 29-33.
KO, W.-K., KIM, S.J., JO, M.-J., CHOI, H., LEE, D., KWON, I.K., LEE, S.-H., HAN, I.-B. and SOHN, S. (2019) Ursodeoxycholic acid inhibits inflammatory responses and promotes functional recovery after spinal cord injury in rats. Molecular Neurobiology, 56,(1), 267-277.
KOTB, M.A. (2012) Molecular mechanisms of ursodeoxycholic acid toxicity & side effects: ursodeoxycholic acid freezes regeneration & induces hibernation mode. International journal of molecular sciences, 13,(7), 8882-8914.
KOZIEL, M.J. Published. Cytokines in viral hepatitis. Seminars in liver disease, 1999. © 1999 by Thieme Medical Publishers, Inc., 157-169.
KRISHNA, K., MRUTHUNJAYA, K. and PATEL, J.A. (2010) Antioxidant and hepatoprotective potential of stem methanolic extract of Justicia gendarussa Burm. IJP-International Journal of Pharmacology, 6,(2), 72-80.
LEE, C.-P., SHIH, P.-H., HSU, C.-L. and YEN, G.-C. (2007) Hepatoprotection of tea seed oil (Camellia oleifera Abel.) against CCl4-induced oxidative damage in rats. Food and chemical toxicology, 45,(6), 888-895.
MADRIGAL-SANTILLÁN, E., MADRIGAL-BUJAIDAR, E., ÁLVAREZ-GONZÁLEZ, I., SUMAYA-MARTÍNEZ, M.T., GUTIÉRREZ-SALINAS, J., BAUTISTA, M., MORALES-GONZÁLEZ, Á., Y GONZÁLEZ-RUBIO, M.G.-L., AGUILAR-FAISAL, J.L. and MORALES-GONZÁLEZ, J.A. (2014) Review of natural products with hepatoprotective effects. World journal of gastroenterology: WJG, 20,(40), 14787.
MENAKAPRIYA, V., KARTHIKARATHI, K., SUBRAMANIAN, R., KATHIRVEL, A. and RAJ, V. (2017) Antioxidant Potential of Stem Bark Extract of Shorea roxburghii against CCl4 induced Liver Damage in Wistar Rats. American Journal of Food and Nutrition, 5,(4), 121-125.
MERLIN, N. and PARTHASARATHY, V. (2011) Antioxidant and hepatoprotective activity of chloroform and ethanol extracts of Gmelina asiatica aerial parts. Journal of Medicinal Plants Research, 5,(4), 533-538.
MOHAMMED SAIF, M., FARID, S.F., KHALEEL, S.A., SABRY, N.A. and EL-SAYED, M.H. (2012) Hepatoprotective efficacy of ursodeoxycholic acid in pediatrics acute lymphoblastic leukemia. Pediatr Hematol Oncol, 29,(7), 627-32.
MRUTHUNJAYA, K. and HUKKERI, V. (2007) Antioxidant and free radical scavenging potential of Justicia gendarussa Burm. leaves in vitro. Natural Product Sciences, 13,(3), 199-206.
MURIEL, P. and RIVERA‐ESPINOZA, Y. (2008) Beneficial drugs for liver diseases. Journal of Applied Toxicology: An International Journal, 28,(2), 93-103.
NIU, F., XU, X., ZHANG, R., SUN, L., GAN, N. and WANG, A. (2019) Ursodeoxycholic acid stimulates alveolar fluid clearance in LPS‐induced pulmonary edema via ALX/cAMP/PI3K pathway. Journal of cellular physiology, 234,(11), 20057-20065.
OZTURK, M., AKDOGAN, M., KESKIN, I., KISIOGLU, A., OZTAS, S. and YILDIZ, K. (2012) Effect of Silybum marianum on acute hepatic damage caused by carbon tetrachloride in rats. Biomedical Research (0970-938X), 23,(2).
PANDIT, A., SACHDEVA, T. and BAFNA, P. (2012) Drug-induced hepatotoxicity: a review. J Appl Pharm Sci, 2,(5), 233-43.
PAPACKOVA, Z., HECZKOVA, M., DANKOVA, H., STICOVA, E., LODEREROVA, A., BARTONOVA, L., PORUBA, M. and CAHOVA, M. (2018) Silymarin prevents acetaminophen-induced hepatotoxicity in mice. PloS one, 13,(1), e0191353.
PRADEEP, K., MOHAN, C.V.R., GOBIANAND, K. and KARTHIKEYAN, S. (2007) Silymarin modulates the oxidant–antioxidant imbalance during diethylnitrosamine induced oxidative stress in rats. European journal of pharmacology, 560,(2-3), 110-116.
RUUTU, T., ERIKSSON, B., REMES, K., JUVONEN, E., VOLIN, L., REMBERGER, M., PARKKALI, T., HÄGGLUND, H. and RINGDÉN, O. (2002) Ursodeoxycholic acid for the prevention of hepatic complications in allogeneic stem cell transplantation. Blood, 100,(6), 1977-1983.
SALAM, O.M.A., SLEEM, A.A., OMARA, E.A. and HASSAN, N.S. (2009) Hepatoprotective effects of misoprostol and silymarin on carbon tetrachloride‐induced hepatic damage in rats. Fundamental & clinical pharmacology, 23,(2), 179-188.
SHENOY, K.A., SOMAYAJI, S. and BAIRY, K. (2001) Hepatoprotective effects of Ginkgo biloba against carbon tetrachloride induced hepatic injury in rats. Indian Journal of Pharmacology, 33,(4), 260-266.
SONG, Z., DEACIUC, I., SONG, M., LEE, D.Y.W., LIU, Y., JI, X. and MCCLAIN, C. (2006) Silymarin protects against acute ethanol‐induced hepatotoxicity in mice. Alcoholism: Clinical and Experimental Research, 30,(3), 407-413.
TALEBIAN, R., PANAHIPOUR, L. and GRUBER, R. (2020) Ursodeoxycholic acid attenuates the expression of proinflammatory cytokines in periodontal cells. Journal of Periodontology.
TESTINO, G., LEONE, S., ANSALDI, F. and BORRO, P. (2013) Silymarin and S-adenosyl-L-methionine (SAMe): two promising pharmacological agents in case of chronic alcoholic hepathopathy. A review and a point of view. Minerva gastroenterologica e dietologica, 59,(4), 341-356.
USTYOL, L., DEMIROREN, K., KANDEMIR, I., ERTEN, R., BULAN, K., KABA, S., DEMIR, N. and BASUNLU, M.T. (2017) Comparative nephroprotective effects of silymarin, N-acetylcysteine, and thymoquinone against carbon tetrachloride-induced nephrotoxicity in rats.
VITAGLIONE, P., MORISCO, F., CAPORASO, N. and FOGLIANO, V. (2005) Dietary antioxidant compounds and liver health. Critical reviews in food science and nutrition, 44,(7-8), 575-586.
WANG, F.S., FAN, J.G., ZHANG, Z., GAO, B. and WANG, H.Y. (2014) The global burden of liver disease: the major impact of China. Hepatology, 60,(6), 2099-2108.
YILMAZ, H.R., SOGUT, S., OZYURT, B., OZUGURLU, F., SAHIN, S., ISIK, B., UZ, E. and OZYURT, H. (2005) The activities of liver adenosine deaminase, xanthine oxidase, catalase, superoxide dismutase enzymes and the levels of malondialdehyde and nitric oxide after cisplatin toxicity in rats: protective effect of caffeic acid phenethyl ester. Toxicology and industrial health, 21,(1-2), 67-73.
YOON, S., JI, S.C., YANG, J., KIM, Y.-K., LEE, S., YU, K.-S., JANG, I.-J., CHUNG, J.-Y. and CHO, J.-Y. (2018) Ursodeoxycholic acid improves liver function via phenylalanine/tyrosine pathway and microbiome remodelling in patients with liver dysfunction. Scientific reports, 8,(1), 1-11.
Copyright (c) 2022 Treefa Farouq Ismail, Hero Muhammed Saed, Zeyan Abdullah Ali, Sarwar Nawzad Jafar
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.