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Biochemical, Immunological, and Histopathological Assessment of Carbon Tetrachloride (CCl₄)-Induced Hepato-Renal Toxicity in Rats

Vol. 2 No. 3 (2025): Desember:

Mervat Kamel Kadhom (1)

(1) Department of Biology, College of Science, University of Al-Qadisiyah, Al-Diwaniyah, Iraq
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Abstract:

General Background Carbon tetrachloride (CCl₄) is a well-established experimental toxicant known to induce liver and kidney injury through oxidative and inflammatory mechanisms. Specific Background CCl₄ metabolism generates reactive free radicals that disrupt biochemical homeostasis, provoke immune imbalance, and produce characteristic histopathological damage in hepatic and renal tissues. Knowledge Gap Despite extensive use of CCl₄ models, integrated evaluation combining biochemical, immunological, and histopathological parameters remains limited. Aims This study aimed to assess dose-dependent hepato-renal toxicity of CCl₄ in rats using biochemical markers, cytokine profiling, and tissue histology. Results CCl₄ exposure increased serum AST, ALT, urea, creatinine, cholesterol, and triglycerides, elevated TNF-α and IL-6, reduced IL-10, and induced marked hepatic and renal histopathological alterations. Novelty The study provides a consolidated multi-system assessment highlighting immune dysregulation alongside biochemical and structural injury. Implications These findings underscore the importance of combined biochemical, immunological, and histopathological approaches for mechanistic evaluation of chemical-induced hepato-renal toxicity.
Keywords : Carbon Tetrachloride Toxicity, Hepatorenal Injury, Oxidative Stress, Proinflammatory Cytokines, Histopathological Alterations
Highlight :












  • Dose-dependent enzyme, lipid, urea, and creatinine elevations indicate progressive liver and kidney dysfunction.




  • Pro-inflammatory mediators increased while anti-inflammatory response declined, demonstrating marked immune imbalance.




  • Tissue examinations revealed cellular degeneration, inflammatory infiltration, fibrosis, and tubular damage severity increased with dose.











References

Faroon, O., Toxicological Profile for Carbon Tetrachloride, Atlanta, GA: Agency for Toxic Substances and Disease Registry, 2005.

Khalaf, T. K., "The Histological Study on the Effects of Carbon Tetrachloride (CCl₄) and Nigella Sativa (NS) on Female Reproductive Organs (Ovary, Ovarian Follicle and Uterus)," M.Sc. thesis, Dept. Biology, Univ. Baghdad, Baghdad, Iraq, 2015.

Azuma, K., Kagi, N., Yanagi, U., and Osawa, H., "Effects of Low-Level Inhalation Exposure to Carbon Dioxide in Indoor Environments: A Short Review on Human Health and Psychomotor Performance," Environment International, vol. 121, pp. 51-56, 2018, doi: 10.1016/j.envint.2018.08.059.

AbouGabal, A. A., Rizk, S. A., and El-Shorbagy, H. M., "The Protective Effect of Black Seed (Nigella Sativa) Against Carbon Tetrachloride-Induced Chromosomal Aberrations and Ultrastructural Changes of Bone Marrow Cells," Arab Journal of Biotechnology, vol. 10, no. 2, pp. 275-288, 2007.

Aslan, A., and Can, M. I., "Milk Thistle Impedes the Development of Carbon Tetrachloride-Induced Liver Damage in Rats Through Suppression of Bcl-2 and Regulating Caspase Pathway," Life Sciences, vol. 117, no. 1, pp. 13-18, 2014, doi: 10.1016/j.lfs.2014.09.019.

Dutta, S., Chakraborty, A. K., Dey, P., Manna, P., Kalita, J., and Saha, C., "Amelioration of CCl₄ Induced Liver Injury in Swiss Albino Mice by Antioxidant Rich Leaf Extract of Croton Bonplandianum Baill," PLoS One, vol. 13, no. 4, p. e0196411, 2018, doi: 10.1371/journal.pone.0196411.

Ali, B. H., "The Effect of Nigella Sativa Oil on Gentamicin Nephrotoxicity in Rats," The American Journal of Chinese Medicine, vol. 32, no. 1, pp. 49-55, 2004, doi: 10.1142/S0192415X04001758.

Megli, F. M., and Sabatini, K., "Mitochondrial Phospholipid Bilayer Structure is Ruined After Liver Oxidative Injury in Vivo," FEBS Letters, vol. 573, no. 1-3, pp. 68-72, 2004, doi: 10.1016/j.febslet.2004.07.055.

Lee, K. J., Choi, J. H., Jeong, H. G., "Protective Effect of Acteoside on Carbon Tetrachloride-Induced Hepatotoxicity," Life Sciences, vol. 74, no. 8, pp. 1051-1064, 2004, doi: 10.1016/j.lfs.2003.07.020.

Elmore, S. A., "Enhanced Histopathology of the Bone Marrow," Toxicologic Pathology, vol. 34, no. 5, pp. 666-686, 2006, doi: 10.1080/01926230600939971.

U.S. Environmental Protection Agency, "Toxicological Review of Carbon Tetrachloride (CAS No. 56-23-5) in Support of Summary Information on the Integrated Risk Information System (IRIS)," Washington, DC: EPA, 2010.

Tsunematsu, S., Sato, S., Iwata, H., Nakajima, T., Fujimoto, J., and Fukushima, S., "Hepatic Tumors Induced by Carbon Tetrachloride in Transgenic Mice Carrying a Human c-H-ras Proto-Oncogene Without Mutations," International Journal of Cancer, vol. 59, no. 4, pp. 554-559, 1994, doi: 10.1002/ijc.2910590420.

Singh, N. D., Kumari, P., and Singh, J., "Clinico-Pathological Alterations in a Case of Bovine Anaplasmosis," Indian Journal of Animal Research, vol. 48, no. 3, pp. 295-297, 2014, doi: 10.5958/j.0976-0555.48.3.062.

Al Za'abi, M., Al Salam, S., Al Suleimani, Y., Ashique, M., Nemmar, A., and Ali, B. H., "Gum Acacia Improves Renal Function and Ameliorates Systemic Inflammation, Oxidative and Nitrosative Stress in Streptozotocin-Induced Diabetes in Rats with Adenine-Induced Chronic Kidney Disease," Cellular Physiology and Biochemistry, vol. 45, no. 6, pp. 2293-2304, 2018, doi: 10.1159/000488176.

Yan, Y., Wang, X. B., Liu, Y. X., and Guan, H. S., "Protective Effects of Chitosan Oligosaccharide and Its Derivatives Against Carbon Tetrachloride-Induced Liver Damage in Mice," Hepatology Research, vol. 35, no. 3, pp. 178-184, 2006, doi: 10.1016/j.hepres.2006.03.009.

Mehmetcik, G., Ozdemirler, G., Kocak-Toker, N., Cevikbas, U., and Uysal, M., "Role of Carnosine in Preventing Thioacetamide-Induced Liver Injury in the Rat," Peptides, vol. 29, no. 3, pp. 425-429, 2008, doi: 10.1016/j.peptides.2007.11.023.

Arici, O. F., and Cetin, N., "Protective Role of Ghrelin Against Carbon Tetrachloride (CCl₄)-Induced Coagulation Disturbances in Rats," Regulatory Peptides, vol. 166, no. 1-3, pp. 139-142, 2011, doi: 10.1016/j.regpep.2010.09.007.

Yacout, G. A., Elguindy, N. M., and El Azab, E. F., "Ameliorative Effect of Zingiber Officinale on Experimentally Induced Liver Fibrosis in Rats," Journal of Medical Research Institute, vol. 28, pp. 154-159, 2007.

Hassan, H. A., and El-Gendy, A. M., "Evaluation of Silymarin and/or Ginger Effect on Induced Hepatotoxicity by Carbon Tetrachloride in Male Albino Rats," The Egyptian Journal of Hospital Medicine, vol. 12, no. 1, pp. 101-112, 2003.

Motawi, T. K., Hamed, M. A., Shabana, M. H., Hashem, R. M., and Aboul Naser, A. F., "Zingiber Officinale Acts as a Nutraceutical Agent Against Liver Fibrosis," Nutrition and Metabolism, vol. 8, no. 40, pp. 1-11, 2011, doi: 10.1186/1743-7075-8-40.

Hsiao, G., Shen, M. Y., Lin, K. H., Lan, M. H., Wu, L. Y., Chou, D. S., Lin, C. H., Su, C. H., and Sheu, J. R., "The Protective Effects of PMC Against Chronic Carbon Tetrachloride-Induced Hepatotoxicity in Vivo," Biological and Pharmaceutical Bulletin, vol. 24, no. 11, pp. 1271-1276, 2001, doi: 10.1248/bpb.24.1271.

Abdou, R. H., Alhamidi, A. A., Almehdar, H., Raza, M., and Boudjelal, M., "Toxicological and Biochemical Studies on Schinus Terebinthifolius Concerning Its Curative and Hepatoprotective Effects Against Carbon Tetrachloride-Induced Liver Injury," Pharmacognosy Magazine, vol. 11, no. Suppl 1, pp. S93-S101, 2015, doi: 10.4103/0973-1296.157705.

El-Kholy, W., Sallam, A. M., Rashed, L. A., and Gaber, O. A., "Immunological Responses in CCl₄-Induced Liver Injury: Role of TNF-α, IL-6, and IL-10," Journal of Immunotoxicology, vol. 17, no. 1, pp. 80-89, 2020, doi: 10.1080/1547691X.2020.1721595.

Popoola, A. B., Ademilusu, E. O., Adedeji, G. B., and Fasanmade, A. A., "Effects of Silymarin on Coagulation Profiles and Osmotic Fragility in Wistar Rats Subjected to CCl₄-Induced Hepatotoxicity," Journal of Basic and Clinical Physiology and Pharmacology, vol. 33, no. 1, pp. 77-85, 2022, doi: 10.1515/jbcpp-2020-0332.

Zhang, L. J., Yu, J. P., Li, D., Huang, Y. H., Yang, H., and Luo, H. S., "Effects of Cytokines on Carbon Tetrachloride-Induced Hepatic Fibrogenesis," Biomedical and Environmental Sciences, vol. 17, no. 2, pp. 111-116, 2004.