Liver condition in rats during the toxigenic period of polychlorinated biphenyl intoxication

Abstract

BACKGROUND: Polychlorinated biphenyls (PCBs) exert diverse toxic effects on humans and animals, leading to disruption of the liver barrier function.

AIM: This study aimed to investigate the dynamics of relative liver mass and liver tissue morphology in experimental rats during the toxigenic period following PCB subacute administration.

METHODS: PCB intoxication was modeled in male Wistar rats (n = 60) weighing 200 ± 15 g and aged 3–4 months. The experimental groups were categorized as follows: Day 1 (n = 10), Day 28 (n = 10), and Day 56 (n = 10). Each experimental group had a corresponding control group (n = 10). The experimental rats (n = 30) received a daily oral administration of oil suspension of PCBs at a dose of 300 mg/kg body weight for 28 days, whereas the control rats received sunflower oil. Liver tissue samples were collected on days 1, 28, and 56 of the experiment for morphological analysis. The relative liver mass and the percentage of normal, abnormal, and degenerative hepatocytes were assessed. Descriptive statistics were applied, including the median Me (Q1 25%, Q3 75%), and the Mann–Whitney U test was used for non-parametric samples. Differences were considered statistically significant at p < 0.05.

RESULTS: On day 1 of the toxigenic period, the relative liver mass of the experimental rats increased by 1.2 times (p = 0.0496) compared with that of the control rats. By day 28, the relative liver mass of the experimental rats significantly decreased by 1.2 times (p = 0.0152) compared with that of the control rats. At the end of the experiment, by day 56, the relative liver mass significantly increased by 1.5 times (p = 0.0049) compared with the control values and by 1.8 times compared with that by day 28 (p = 0.0036). Morphological analysis of the liver tissue in experimental rats revealed abnormally enlarged hepatocytes (14%) on day 1 following the cessation of PCB administration. During the toxigenic period, the number of these cells increased to 35% on day 28 (p = 0.0002) and 47% on day 56 (p = 0.0002). At the end of the study, necrotically altered hepatocytes accounted for 22% of the total hepatocytes. Lymphoid cells were diffusely distributed along the intralobular sinusoidal capillaries and were present in the interlobular loose connective tissue within the portal zones of the liver.

CONCLUSION: In experimental animals with subacute PCB intoxication, inflammatory and destructive histomorphological changes were observed in the liver, along with an increase in the relative liver mass.

Keywords

polychlorinated biphenyls / liver / rat / intoxication / ecology

References

[1] Kayumova AF, Gabdulkhakova IR, Bogdanova AV, et al. The delayed consequences of erythropoiesis in erythroblastic islands in rats’ bone marrow after exposure to polychlorinated biphenyls with a dose of 1/20 LD50. Vyatskij medicinskij vestnik. 2017;53(1):33–38. (In Russ.) EDN: YTPJED

[2] Каюмова А.Ф., Габдулхакова И.Р., Богданова А.В., и др. Отдаленные последствия эритропоэза в эритробластических островках костного мозга крыс после воздействия полихлорированных бифенилов в дозе 1/20 LD50 // Вятский медицинский вестник. 2017. Т. 53, № 1. С. 33–38. EDN: YTPJED

[3] EFSA Panel on Contaminants in the Food Chain (CONTAM); Knutsen HK, Alexander J, et al. Risk for animal and human health related to the presence of dioxins and dioxin-like PCBs in feed and food. EFSA J. 2018;16(11):5333. doi: 10.2903/j.efsa.2018.5333

[4] EFSA Panel on Contaminants in the Food Chain (CONTAM); Knutsen H.K., Alexander J., et al. Risk for animal and human health related to the presence of dioxins and dioxin-like PCBs in feed and food // EFSA J. 2018. Vol. 16, N. 11. P. 5333. doi: 10.2903/j.efsa.2018.5333

[5] Gabdulkhakova IR, Kayumova AF, Samokhodova OV. The effect of different doses of PCBS on the condition of spontaneous and induced immunoglobulin luminol-dependent chemiluminescence of whole blood. Bashkortostan Medical Journal. 2016;11(1(61)):129–132. (In Russ.) EDN: VVBJCP

[6] Габдулхакова И.Р., Каюмова А.Ф., Самоходова О.В. Влияние различных доз полихлорированных бифенилов на состояние спонтанной и индуцированной иммуноглобулином люминолзависимой хемилюминесценции цельной крови // Медицинский вестник Башкортостана. 2016. Т. 1, № 1 (61). С. 129–132. EDN: VVBJCP

[7] Gainullina AA, Kamilov FKh, Kayumova AF, et al. Activity of antioxidant enzymes in the liver and brain in rats in the recovery period after subacute intoxication with polychlorobiphenyls. Medical science and education of the Urals. 2012;13(3–1(71)):60–62. (In Russ.) EDN: TAFNWP

[8] Гайнуллина А.А., Камилов Ф.Х., Каюмова А.Ф., и др. Активность антиоксидантных ферментов в печени и головном мозге у крыс в восстановительном периоде после подострой интоксикации полихлорбифенилами // Медицинская наука и образование Урала. 2012. Т. 13, № 3–1 (71). С. 60–62. EDN: TAFNWP

[9] Klyuev NA, Brodsky ES. Determination of polychlorinated biphenyls in the environment and biota. In: Polychlorinated biphenyls. Supertoxicants of the XXI century. Information issue N. 5. Moscow: VINITI, 2000. P. 31–63. (In Russ.)

[10] Клюев Н.А., Бродский Е.С. Определение полихлорированных бифенилов в окружающей среде и биоте. В кн.: Полихлорированные бифенилы. Супертоксиканты ХХI века. Информ. вып. № 5. Москва: ВИНИТИ, 2000. С. 31–63.

[11] Grimm FA, Hu D, Kania-Korwel I, et al. Metabolism and metabolites of polychlorinated biphenyls (PCBs). Crit Rev Toxicol. 2015;45(3):245–272. doi: 10.3109/10408444.2014.999365

[12] Grimm F.A., Hu D., Kania-Korwel I., et. al. Metabolism and metabolites of polychlorinated biphenyls (PCBs) // Crit Rev Toxicol. 2015. Vol. 45, N. 3. P. 245–272. doi: 10.3109/10408444.2014.999365

[13] Kayumova AF, Gabdulhakova IR, Bogdanova AV, et al. Erythropoiesis in erythroblastic bone marrow islets during toxigenic period after exposure to different polychlorinated biphenyls doses. Perm medical journal. 2016;33(2):90–97. EDN: VVCSIJ

[14] Каюмова А.Ф., Габдулхакова И.Р., Богданова А.В., и др. Эритропоэз в эритробластических островках костного мозга в токсигенном периоде после воздействия разных доз полихлорированных бифенилов // Пермский медицинский журнал. 2016. Т. 33, № 2. С. 90–97. EDN: VVCSIJ

[15] Chereshnev VA, Yushkov BG, Sumin MN, et al. System of blood and adaptation of the organism to extreme factors. Russian journal of physiology. 2004;90(10):1193–1202. EDN: SCDZVZ

[16] Черешнев В.А., Юшков Б.Г., Сумин М.Н., и др. Система крови и адаптация организма к экстремальным факторам // Российский физиологический журнал им. И.М. Сеченова. 2004. Т. 90, № 10. С. 1193–1202. EDN: SCDZVZ

[17] Chuikin OS, Shakirova GR, Kudashkina NV, et al. Histochemical changes in the tooth and jaw germs of laboratory rats under the influence of ecotoxicants and during perinatal prevention. Pediatric dentistry and dental prophylaxis. 2023;23(2):114–123. doi: 10.33925/1683-3031-2023-578

[18] Чуйкин О.С., Шакирова Г.Р., Кудашкина Н.В., и др. Гистохимические изменения зачатков зубов и челюстей лабораторных крыс при воздействии экотоксикантов и при перинатальной профилактике // Стоматология детского возраста и профилактика. 2023. Т. 23, № 3. С. 114–123. doi: 10.33925/1683-3031-2023-578

[19] Gainullina AA, Galeev EA, Kayumova AF. Changes in body weight and relative liver weight in rats after subacute administration of polychlorinated biphenyls. In: XV International Scientific and Practical Conference “Scientific Prospects of the XXI Century. Achievements and Prospects of the New Century”; 2015 Oct 16–17, Novosibirsk. P. 60–62. (In Russ.). EDN: ZVQUST

[20] Гайнуллина А.А., Галеев Э.А. Каюмова А.Ф. Изменения массы тела и относительной массы печени крыс после подострого введения полихлорированных бифенилов. В кн.: XV Международная научно-практическая конференция «Научные перспективы XXI века. Достижения и перспективы нового столетия»; 16–17 октября 2015 г.; Новосибирск. С. 60–62. EDN: ZVQUST

[21] Eselevich SA, Badmaeva BB, Kurshakov VS. Professional toxic liver diseases. In: Current issues of occupational medicine in the context of a new coronavirus infection. Collection of papers of the correspondence scientific and practical conference. St. Petersburg, 2022. P. 75–92. (In Russ.) EDN: DRMANV

[22] Еселевич С.А., Бадмаева Б.Б., Куршаков В.С. Профессиональные токсические заболевания печени. В кн.: Актуальные вопросы медицины труда в условиях новой коронавирусной инфекции. Сборник трудов заочной научно-практической конференции. Санкт-Петербург; 2022. С. 75–92. EDN: DRMANV

[23] Chuikin OS, Shakirova GR, Zulkarnaev TR, et al. Influence of ecotoxicants on the tooth groups of laboratory animals. Actual problems of dentistry. 2022;18(4):134–140. doi: 10.18481/2077-7566-2022-18-4-134-140

[24] Чуйкин О.С., Шакирова Г.Р., Зулькарнаев Т.Р., и др. Влияние экотоксикантов на зачатки зубов лабораторных животных // Проблемы стоматологии. 2022. Т. 18. № 4. С. 134–140. doi: 10.18481/2077-7566-2022-18-4-134-140

[25] Chuikin OS, Musina LA, Galiakhmetova EKh, et al. Morphological changes in liver tissues of rats under the exposure of ecotoxicants and perinatal prophylaxis. Morphology. 2022;160(4):215–224. doi: 10.17816/morph.2965

[26] Чуйкин О.С., Мусина Л.А., Галиахметова Э.Х., и др. Морфологические изменения тканей печени лабораторных крыс при воздействии экотоксикантов и при перинатальной профилактике // Морфология. 2022. Т. 160, № 4. С. 215–223. doi: 10.17816/morph.2965

[27] Buha A, Antonijević B, Milovanović V, et. al. Polychlorinated biphenyls as oxidative stress inducers in liver of subacutely exposed rats: implication for dose-dependence toxicity and benchmark dose concept. Environ Res. 2015:136:309–17. doi: 10.1016/j.envres.2014.11.005

[28] Buha A., Antonijević B., Milovanović V., et. al. Polychlorinated biphenyls as oxidative stress inducers in liver of subacutely exposed rats: implication for dose-dependence toxicity and benchmark dose concept // Environ Res. 2015. Vol. 136. P. 309–317. doi: 10.1016/j.envres.2014.11.005

[29] Zarerad E, Niksalehi K, Armandeh M. Polychlorinated Biphenyls: A Review of Recent Updates on Food Safety and Environmental Monitoring, Health and Toxicological Implications, and Analysis. Mini Rev Med Chem. 2023;23(13):1390–1411. doi: 10.2174/1389557523666221213091445

[30] Zarerad E., Niksalehi K., Armandeh M., et. al. Polychlorinated Biphenyls: A Review of Recent Updates on Food Safety and Environmental Monitoring, Health and Toxicological Implications, and Analysis // Mini Rev Med Chem. 2023. Vol. 23, N. 13. P. 1390–1411. doi: 10.2174/1389557523666221213091445

[31] Liu J, Tan Y, Song E, et. al. A Critical Review of Polychlorinated Biphenyls Metabolism, Metabolites, and Their Correlation with Oxidative Stress. Chem Res Toxicol. 2020;33(8):2022–2042. doi: 10.1021/acs.chemrestox.0c00078

[32] Liu J., Tan Y., Song E., et. al. A Critical Review of Polychlorinated Biphenyls Metabolism, Metabolites, and Their Correlation with Oxidative Stress // Chem Res Toxicol. 2020. Vol. 33, N. 8. P. 2022–2042. doi: 10.1021/acs.chemrestox.0c00078

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