Kadmiyumun Neden Olduğu Karaciğer Hasarında CD34, CD68 ve CD3 İmmunekspresyonları ve Arı Ekmeğinin (Perga) Koruyucu Etkinliği

Year 2024, , 1001 - 1013, 12.10.2024

Turan Yaman , Turan Akkoyun , Ömer Faruk Keleş , Mahire Bayramoğlu Akkoyun

https://doi.org/10.30910/turkjans.1518973

Abstract

Kadmiyum (Cd), karaciğer de dahil olmak üzere vücudun birçok organında oksidatif strese neden olan güçlü çevresel toksik maddelerden biridir. Perga (Arı ekmeği), tıbbi özellikleri nedeniyle apiterapötik amaçlarla kullanılmaktadır. Bu çalışma, Cd maruziyeti sonucu karaciğerde meydana gelen endotelyal hasar ve yangısal hücre aktivasyonu üzerine perganın etkinliğini araştırmak amacıyla yapıldı. Bu amaçla 32 adet erkek wistar sıçan rastgele kontrol, perga (0.5 g/kg perga), Cd (5 mg/kg CdCl2) ve perga + Cd (0.5 g/kg perga + 5 mg/kg CdCl2) olmak üzere 4 gruba (8 sıçan/grup) ayrıldı. Dört hafta boyunca günlük intragastrik Cd ve/veya perga uygulandı. Çalışma sonunda ratlar sakrifiye edilerek karaciğer doku kesitleri hematoksilen-eozin ve Masson’s Trichrom ile boyandı. İmmunohistokimyasal olarak karaciğer sinüzoidal endotelindeki reaktivite CD34, Kupffer hücrelerindeki reaktivite CD68 ve T-lenfosit hücrelerinin seviyeleri CD3 antikorları kullanılarak belirlendi. Cd'ye maruz kalma, karaciğer önemli histolojik değişikliklere neden oldu. İmmunohistokimyasal olarak Cd maruziyeti CD34, CD68 ve CD3 ekspresyonlarında artışa neden oldu. Öte yandan, Cd ve perga'nin birlikte işlenmesi bazı histopatolojik değişiklikleride kısmi iyileşmeye neden oldu. Cd grubu ile kıyaslandığında, Cd + perga grubunda CD34 ve CD68 pozitifliğinde azalma meydana gelirken gruplar arasında CD3 pozitif hücrelerin sayısında analamlı bir farklılık tepit edilmedi. Sonuçlar, rat karaciğerinde meydana gelen histopatolojik değişikliklerin ve yangının perga takviyesi ile kısmen iyileşme gösterebileceğini ortaya koydu.

Keywords

Kadmiyum, perga, karaciğer, immunohistokimya, rat.

Immunoexpression of CD34, CD68 and CD3 in Cadmium-Induced Liver Damage and Protective Effectiveness of Bee Bread (Perga)

Abstract

Cadmium (Cd) is one of the potent environmental toxicants that causes oxidative stress in many organs of the body, including the liver. Perga (bee bread) is used for apitherapeutic purposes due to its medicinal properties. This study was conducted to investigate the effectiveness of perga on endothelial damage and inflammatory cell activation in the liver as a result of exposure to Cd. For this purpose, 32 male Wistar rats (8 rats/group) were randomly divided into 4 groups, as the control, perga (0.5 g/kg of perga), Cd (5 mg/kg of CdCl2), and Cd + perga (0.5 g/kg of perga + 5 mg/kg of CdCl2) groups. Daily intragastric Cd and/or perga was administered for 4 weeks. At the end of the study, the rats were euthanized and liver tissue sections were taken and stained with hematoxylin-eosin and Masson’s Trichrome. Immunohistochemically, the reactivity of the liver sinusoidal endothelium was determined using CD34, the reactivity of the Kupffer cells was determined using CD68, and the levels of T-lymphocyte cells were determined using CD3 antibodies. Exposure to Cd caused significant histological changes in the liver. Immunohistochemically, exposure to Cd caused an increase in the expressions of CD34, CD68, and CD3. On the other hand, the cotreatment of Cd and perga caused partial improvement in some histopathological changes. Compared to the Cd group, there was a decrease in CD34 and CD68 positivity in the Cd + perga group, while no significant difference was detected in the number of CD3-positive cells between the groups. The results revealed that the histopathological changes and inflammation in the rat liver could partially improve with perga supplementation.

Keywords

Cadmium, perga, liver, immunohistochemistry, rat

Ethical Statement

The local ethics committee of Van Yüzüncü Yıl University Animal Experiments approved this study (27/06/2024, 2024/06-11).

References

• Arakelian, L., Lion, J., Churlaud, G., Bargui, R., Thierry, B., Mutabazi, E., Bruneval. P., Alberdi, A. S., Doliger, C., Veyssiere, M., Larghero. J., and Mooney, N. 2023. Endothelial CD34 expression and regulation of immune cell response in-vitro. Scientific Reports, 13(1), 13512.
• Baskaran, R., Priya, L. B., Kumar, V. S., and Padma, V. V. 2018. Tinospora cordifolia extract prevents cadmium-induced oxidative stress and hepatotoxicity in experimental rats. Journal of Ayurveda and Integrative Medicine, 9(4), 252-257.
• Chan, C. C., Cheng, L. Y., Lin, C. L., Huang, Y. H., Lin, H. C., and Lee, F. Y. 2011. The protective role of natural phytoalexin resveratrol on inflammation, fibrosis and regeneration in cholestatic liver injury. Molecular Nutrition & Food Research, 55(12), 1841-1849.
• Choi, J. H., Rhee, I. K., Park, K. Y., Park, K. Y., Kim, J. K., and Rhee, S. J. 2003. Action of green tea catechin on bone metabolic disorder in chronic cadmium-poisoned rats. Life Sciences, 73(12), 1479-1489.
• Deniz, O. G., Eren, B., and Sagir, D. 2021. Possible protective role of selenium against liver toxicity induced by cadmium in rats. Medicine Science, 10(2), 444-449.
• Djokic, J., Popov Aleksandrov, A., Ninkov, M., Mirkov, I., Zolotarevski, L., Kataranovski, D., and Kataranovski, M. 2015. Cadmium administration affects circulatory mononuclear cells in rats. Journal of Immunotoxicology, 12(2), 115-123.
• El-Mansy, A. A., Mazroa, S. A., Hamed, W. S., Yaseen, A. H., and El-Mohandes, E. A. (2016). Histological and immunohistochemical effects of Curcuma longa on activation of rat hepatic stellate cells after cadmium induced hepatotoxicity. Biotechnic & Histochemistry, 91(3), 170-181.
• El-Sokkary, G. H., Nafady, A. A., and Shabash, E. H. 2010. Melatonin administration ameliorates cadmium-induced oxidative stress and morphological changes in the liver of rat. Ecotoxicology and Environmental Safety, 73(3), 456-463.
• Famurewa, A. C., Ugwu-Ejezie, C. S., Iyare, E. E., Folawiyo, A. M., Maduagwuna, E. K., and Ejezie, F. E. 2021. Hepatoprotective effect of polyphenols isolated from virgin coconut oil against sub-chronic cadmium hepatotoxicity in rats is associated with improvement in antioxidant defense system. Drug and Chemical Toxicology, 44(4), 418-426.
• Fang, J., Yin, H., Yang, Z., Tan, M., Wang, F., Chen, K., Zuo, Z., Shu, G., Cui, H., Ouyang P, Guo, H., Chen, Z., Huang, C., Geng, Y., and Liu, W. 2021. Vitamin E protects against cadmium-induced sub-chronic liver injury associated with the inhibition of oxidative stress and activation of Nrf2 pathway. Ecotoxicology and Environmental Safety, 208, 111610.
• Flora, S. J. S., Mehta, A., Gautam, P., Jatav, P. C., and Pathak, U. 2007. Essential metal status, prooxidant/antioxidant effects of MiADMSA in male rats: age-related effects. Biological Trace Element Research, 120, 235-247.
• Friedman, S. L. 2000. Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. Journal of Biological Chemistry, 275(4), 2247-2250.
• Gehring, S., Dickson, E. M., Papa, E. F., Harty, M. W., Tracy jr, T. F., and Gregory, S. H. 2006. Kupffer cells abrogate cholestatic liver injury in mice. Journal of Pediatric Gastroenterology and Nutrition, 42(5), E79.
• Hassoun, E. A., and Stohs, S. J. 1996. Cadmium-induced production of superoxide anion and nitric oxide, DNA single strand breaks and lactate dehydrogenase leakage in J774A. 1cell cultures. Toxicology, 112(3), 219-226.
• He, X., Qi, Z., Hou, H., Gao, J., and Zhang, X. X. 2020. Effects of chronic cadmium exposure at food limitation-relevant levels on energy metabolism in mice. Journal of Hazardous Materials, 388, 121791.
• Karbownik, M., Gitto, E., Lewinski, A., and Reiter, R. J. 2001. Induction of lipid peroxidation in hamster organs by the carcinogen cadmium: amelioration by melatonin. Cell Biology and Toxicology, 17, 33-40.
• Kataranovski, M., Janković, S., Kataranovski, D., Stošić, J., and Bogojević, D. 2009. Gender differences in acute cadmium-induced systemi inflammation in rats. Biomedical and Environmental Sciences, 22(1), 1-7.
• Kawanami, Y., Kitazawa, R., Haraguchi, R., Ueda, Y., Nishi, Y., Ariyasu, K., Mizuno Y and Kitazawa, S. 2016. Hepatic sinusoidal obstruction syndrome without preceding medical events. Case Reports in Clinical Medicine, 5(3), 105-108.
• Kayama, F., Yoshida, T., Elwell, M. R., and Luster, M. I. 1995. Role of tumor necrosis factor-α in cadmium-induced hepatotoxicity. Toxicology and Applied Pharmacology, 131(2), 224-234.
• McKim Jr, J. M., Liu, J., Liu, Y. P., and Klaassen, C. D. 1992. Distribution of cadmium chloride and cadmium-metallothionein to liver parenchymal, Kupffer, and endothelial cells: their relative ability to express metallothionein. Toxicology and Applied Pharmacology, 112(2), 324-330.
• Miltonprabu, S., and Manoharan, V. 2016. Hepatoprotective effect of grape seed proanthocyanidins on Cadmium-induced hepatic injury in rats: possible involvement of mitochondrial dysfunction, inflammation and apoptosis. Toxicology Reports, 3, 63-77.
• Nolan, C. V., and Shaikh, Z. A. 1986. The vascular endothelium as a target tissue in acute cadmium toxicity. Life sciences, 39(16), 1403-1409.
• Omar, N. M., and Mohammed, M. A. 2017. The impact of black seed oil on tramadol-induced hepatotoxicity: Immunohistochemical and ultrastructural study. Acta Histochemica, 119(5), 543-554.
• Othman, Z. A., Noordin, L., Ghazali, W. S. W., Omar, N., and Mohamed, M. 2019. Nutritional, phytochemical and antioxidant analysis of bee bread from different regions of Malaysia. Indian Journal of Pharmaceutical Sciences, 81(5), 955-960.
• Rahimzadeh, M. R., Rahimzadeh, M. R., Kazemi, S., and Moghadamnia, A. A. 2017. Cadmium toxicity and treatment: An update. Caspian Journal of Internal Medicine, 8(3), 135.
• Rikans, L. E., and Yamano, T. 2000. Mechanisms of cadmium‐mediated acute hepatotoxicity. Journal of Biochemical and Molecular Toxicology, 14(2), 110-117.
• Rinaldi, M., Micali, A., Marini, H., Adamo, E.B., Puzzolo, D., Pisani, A., Trichilo, V., Altavilla, D., Squadrito, F., and Minutoli, L. 2017. Cadmium, organ toxicity and therapeutic approaches: a review on brain, kidney and testis damage. Current Medicinal Chemistry, 24 (35), 3879–3893.
• Roberts, R. A., Ganey, P. E., Ju, C., Kamendulis, L. M., Rusyn, I., and Klaunig, J. E. 2007. Role of the Kupffer cell in mediating hepatic toxicity and carcinogenesis. Toxicological Sciences, 96(1), 2-15.
• Sanjeev, S., Bidanchi, R. M., Murthy, M. K., Gurusubramanian, G., and Roy, V. K. 2019. Influence of ferulic acid consumption in ameliorating the cadmium-induced liver and renal oxidative damage in rats. Environmental Science and Pollution Research, 26(20), 20631-20653.
• Sauer, J. M., Waalkes, M. P., Hooser, S. B., Kuester, R. K., McQueen, C. A., and Sipes, I. G. 1997. Suppression of Kupffer cell function prevents cadmium induced hepatocellular necrosis in the male Sprague-Dawley rat. Toxicology, 121(2), 155-164.
• Sobral, F., Calhelha, R. C., Barros, L., Dueñas, M., Tomás, A., Santos-Buelga, C., Vilas-Boas, M., and Ferreira, I. C. F. R. 2017. Flavonoid composition and antitumor activity of bee bread collected in northeast Portugal. Molecules, 22(2), 248.
• Stohs, S. J., Bagchi, D., Hassoun, E., and Bagchi, M. 2001. Oxidative mechanisms in the toxicity of chromium and cadmium ions. Journal of Environmental Pathology, Toxicology and Oncology, 20(2).
• Suleiman, J. B., Abu Bakar, A. B., Noor, M. M., Nna, V. U., Othman, Z. A., Zakaria, Z., Eleazu ,C. O., and Mohamed, M. 2021. Bee bread mitigates downregulation of steroidogenic genes, decreased spermatogenesis, and epididymal oxidative stress in male rats fed with high-fat diet. American Journal of Physiology-Endocrinology and Metabolism, 321(3), E351-E366.
• Tripathi, S., and Srivastav, A. K. 2011. Cytoarchitectural alterations in kidney of Wistar rat after oral exposure to cadmium chloride. Tissue and Cell, 43(2), 131-136.
• Urcan, A. C., Criste, A. D., Dezmirean, D. S., Mărgăoan, R., Caeiro, A., and Graça Campos, M. 2018. Similarity of data from bee bread with the same taxa collected in India and Romania. Molecules, 23(10), 2491.
• Vicente-Sánchez, C., Egido, J., Sánchez-González, P. D., Pérez-Barriocanal, F., López-Novoa, J. M., and Morales, A. I. 2008. Effect of the flavonoid quercetin on cadmium-induced hepatotoxicity. Food and Chemical Toxicology, 46(6), 2279-2287.
• Vrba, J., and Modriansky, M. 2002. Oxidative burst of Kupffer cells: target for liver injury treatment. Biomedical Papers-Palacky University in Olomouc, 146(2), 15-20.
• Waisberg, M., Joseph, P., Hale, B., and Beyersmann, D. 2003. Molecular and cellular mechanisms of cadmium carcinogenesis. Toxicology, 192(2-3), 95-117.
• Wang, X. Y., Wang, Z. Y., Zhu, Y. S., Zhu, S. M., Fan, R. F., and Wang, L. 2018. Alleviation of cadmium‐induced oxidative stress by trehalose via inhibiting the Nrf2‐Keap1 signaling pathway in primary rat proximal tubular cells. Journal of Biochemical and Molecular Toxicology, 32(1), e22011.
• Wood, H. B., May, G., Healy, L., Enver, T., and Morriss-Kay, G. M. 1997. CD34 expression patterns during early mouse development are related to modes of blood vessel formation and reveal additional sites of hematopoiesis. Blood, The Journal of the American Society of Hematology, 90(6), 2300-2311.
• Yaman, T., Akkoyun, H. T., Bayramoğlu Akkoyun, M., Karagözoğlu, F., Melek, Ş., Keleş, Ö. F., and Bengü, A. Ş. 2024b. Assessment of the effect of sodium tetraborate on oxidative stress, inflammation, and apoptosis in lead-induced nephrotoxicity. Drug and Chemical Toxicology, 1-13.
• Yaman, T., Akkoyun, H. T., Keleş, Ö. F., and Bayramoğlu, M. 2024a. Effect of bee bread (perga) on histopathological changes and immunohistochemical expression of apoptosis markers in the kidney of rats exposed to cadmium. Van Veterinary Journal, 35(2), 101-108.
• Yamano, T., Shimizu, M., and Noda, T. 1998. Age-related change in cadmium-induced hepatotoxicity in Wistar rats: role of Kupffer cells and neutrophils. Toxicology and Applied Pharmacology, 151(1), 9-15.
• Ye, J. L., Mao, W. P., Wu, A. L., Zhang, N. N., Zhang, C., Yu, Y. J., Zhou, L., and Wei, C. J. 2007. Cadmium-induced apoptosis in human normal liver L-02 cells by acting on mitochondria and regulating Ca2+ signals. Environmental Toxicology and Pharmacology, 24(1), 45-54.
• Zakaria, Z., Othman, Z. A., Suleiman, J. B., Che Jalil, N. A., Ghazali, W. S. W., Nna, V. U., and Mohamed, M. 2021. Hepatoprotective effect of bee bread in metabolic dysfunction-associated fatty liver disease (MAFLD) rats: Impact on oxidative stress and inflammation. Antioxidants, 10(12), 2031.
• Zhang, Y., Yu, X., Sun, S., Li, Q., Xie, Y., Li, Q., Zhao, Y., Pei, J., Zhang, W., Xue, P., Zhou, Z., and Zhang, Y., 2016. Cadmium modulates hematopoietic stem and progenitor cells and skews toward myelopoiesis in mice. Toxicology and Applied Pharmacology, 313, 24–34.