اثر تعدیلکننده گیاهی بر بیان NF-κB و IL-1β و تغییرات آسیبشناسی بافتی در آسیب کبدی–کلیوی ناشی از کلرید کادمیوم در موشهای صحرایی تیمارشده با Aframomum melegueta و Rauvolfia vomitoria
DOI::
https://doi.org/10.22100/jkh.v21i1.3566کلمات کلیدی:
سمیت کادمیوم, بهداشت محیط, آسیب کبدی-کلیوی, ایمونومدولاسیون, استرس اکسیداتیوچکیده
مقدمه: کادمیوم که توسط آژانس بینالمللی تحقیقات سرطان (IARC) بهعنوان سرطانزای انسانی گروه ۱ طبقهبندی شده است، عمدتاً از طریق القای استرس اکسیداتیو، تولید بیش از حد گونههای فعال اکسیژن (ROS) و تحریک پاسخهای التهابی موجب آسیب چند اندامی، بهویژه در کبد و کلیهها، میشود. در این مطالعه، تغییرات مولکولی و آسیبشناختی ناشی از سمیت کبدی–کلیوی القا شده با کلرید کادمیوم (CdCl₂) و اثرات محافظتی عصارههای متانولی Aframomum melegueta و Rauvolfia vomitoria در موشهای صحرایی نر نژاد ویستار بررسی شد.
مواد و روشها: این مطالعه مقطعی بر روی ۴۰۰ فرد بالغ مبتلا به HIV تحت درمان با HAART در بیمارستان نیروی دریایی نیجریه، واری، انجام شد. شرکتکنندگان بر اساس مدت دریافت HAART به سه گروه (≤۲ سال، ۲ تا ۵ سال و >۵ سال) تقسیم شدند. دادههای جمعیتشناختی، BMI، پروفایل چربی (کلسترول تام، LDL-C، HDL-C و تریگلیسرید)، قند خون ناشتا و HbA1c ارزیابی و ارتباط مدت درمان HAART با بیماریهای قلبی- متابولیک با استفاده از رگرسیون لجستیک چندمتغیره و تعدیل متغیرهای مخدوشکننده بررسی شد.
نتایج: مواجهه با CdCl₂ موجب افزایش معنیدار بیان NFκB و IL-1β شد (05/0>P) که نشاندهنده افزایش پاسخهای پیامرسانی التهابی و آسیب بافتی است. تیمار با هر یک از عصارههای A. melegueta یا R. vomitoria موجب کاهش معنیدار بیان NFκB و IL-1β و بهبود تغییرات آسیبشناختی بافتی ناشی از CdCl₂ شد؛ با این حال، تجویز همزمان دو عصاره اثر محافظتی بیشتری نشان نداد.
بحث: صارههای A. melegueta و R. vomitoria میتوانند با تعدیل مسیرهای التهابی NFκB و IL-1β، اثرات محافظتی در برابر سمیت کبدی–کلیوی ناشی از CdCl₂ ایجاد کنند؛ با این حال، استفاده ترکیبی از آنها مزیت درمانی بیشتری نسبت به مصرف جداگانه نشان نداد.
مراجع
Edo GI, Itoje-akpokiniovo LO, Obasohan P, Ikpekoro VO, Samuel PO, Jikah AN, et al. Impact of environmental pollution from human activities on water, air quality and climate change. Ecological Frontiers 2024;44:874-89. doi: 10.1016/j.ecofro.2024.02.014
Moronkeji A, Akinbo FO. Genotoxic Response and Histological Alterations in Rat Lungs Exposed to Gasoline Generator Exhaust. Sultan Qaboos University Journal for Science [SQUJS]. 2024;29:15-27. doi: 10.53539/squjs.vol29isspp15-27
Moronkeji A, Olayanju A, Adeniyi TD, Atere AD, Moronkeji AI, Igunbor MC, et al. Oxidative stress response to gasoline generator exhaust emission in adult male wistar rats. Environmental Analysis Health and Toxicology 2024;39:e2024030. doi: 10.5620/eaht.2024030
Adeniyi T, Moronkeji A, Ekundina V. Histological evaluation of the liver, kidney, and testes of adult male Wistar rats exposed to heavy metals-contaminated waterways. Medical Laboratory Journal 2023;17:4-8. doi: 10.61186/mlj.17.5.4
Briffa J, Sinagra E, Blundell R. Heavy metal pollution in the environment and their toxicological effects on humans. Heliyon 2020;6:e04691. doi: 10.1016/j.heliyon.2020.e04691
Adeniyi TD, Achukwu PU, Abubakar AA, Adekomi AD. Heavy metals obtained from waterways induced neurodegeneration in the prefrontal cortex of Wistar rats. European Journal of Anatomy 2019;23:65-76.
Rasin P, Ashwathi AV, Basheer SM, Haribabu J, Santibanez JF, Garrote CA, et al. Exposure to cadmium and its impacts on human health: A short review. Journal of Hazardous Materials Advances 2025;17:100608. doi: 10.1016/j.hazadv.2025.100608
Yang Y, Hassan MF, Ali W, Zou H, Liu Z, Ma Y. Effects of Cadmium Pollution on Human Health: A Narrative Review. Atmosphere 2025;16:225. doi: 10.3390/atmos16020225
Xu W, Wang S, Ruan W, Hao M, Jiang K, Guo H, et al. Cadmium exposure and health outcomes: An umbrella review of meta-analyses. Environ Res. 2025;276:121547. doi: 10.1016/j.envres.2025.121547
Umber J, Qasim M, Ashraf S, Ashfaq UA, Mahmood-ur-Rahman, Iram A, et al. Antioxidants Mitigate Oxidative Stress: A General Overview. In: Imran, A., Hussain, G. (eds) The Role of Natural Antioxidants in Brain Disorders. Food Bioactive Ingredients Springer, Cham 2023;149-69. doi: 10.1007/978-3-031-41188-5_7
Moronkeji A, Daniel Adeniyi T, Ayobami Fasogbon S, Olayinka Ajala J, Tolulope Adegoke E, Williams CE, et al. Histopathological Perspectives on Toxic Environmental Pollutants: Cellular Damage Pathways and Strategic Interventions in Mammalian Systems. In: Suna Sabuncuoğlu and Onur Kenan Ulutaş (eds) Environmental Toxicology - Understanding, Impact, and Mitigation Strategies for a Sustainable Future. IntechOpen; 2025. doi: 10.5772/intechopen.1012228
Moronkeji A, Eze IG, Bejide RA, Anwara OA, Igunbor MC. Evaluation of herbal cocktail used in the treatment of malaria on liver tissue of adult Wistar rats. Journal of Medicinal Plants Research 2018;12:508-521. doi: 10.5897/JMPR2018.6661
Ogwiji M, Ajao OF, Okwanya MI, Mbaya YP. Beneficial activities of ethnobotanical plants on selected systems and agriculture. Journal of Medicinal Plants Studies 2023;11:85-95. doi: 10.22271/plants.2023.v11.i5b.1589
Muscolo A, Mariateresa O, Giulio T, Mariateresa R. Oxidative Stress: The Role of Antioxidant Phytochemicals in the Prevention and Treatment of Diseases. Int J Mol Sci 2024;25:3264. doi: 10.3390/ijms25063264
Akinpelu M, Adeniyi T, Abiodun O, Chuks IM, Joy A, Toluwanimi A, et al. Cymbopogon citratus: A Modulator of TNF-α and IL-10 in NSAID-Induced Hepatorenal Toxicity in Adult Wistar Rats. Bulletin of Pharmaceutical Sciences Assiut University 2024;47:1251-62. doi: 10.21608/bfsa.2024.297319.2162
Moronkeji A, Adeniyi T, Olubunmi E, Kayode I, Ajala OJ, Moronkeji AI, et al. Modulatory effects of Aframomum melegueta and Rauvolfia vomitoria in cadmium-induced renal toxicity in adult rats. J Cell Biotechnol 2025;11:3-13. doi: 10.1177/23523689251329719
Kumar S, Kumari D, Singh B. Genus Rauvolfia: A review of its ethnopharmacology, phytochemistry, quality control/quality assurance, pharmacological activities and clinical evidence. J Ethnopharmacol 2022;295:115327. doi: 10.1016/j.jep.2022.115327
Dong R, Chen P, Chen Q. Inhibition of pancreatic cancer stem cells by Rauwolfia vomitoria extract. Oncol Rep 2018;40:3144-54. doi: 10.3892/or.2018.6713
Iwu Irenus C, Chinonye C, C. Samuel I, Obiagwu I, Uchenna OL, Ukaoma AA, Chijioke-Okere Maureen and Ezekoye. Miracle oluchukwu. chemical and medicinal properties of rauwolfia vomitoria (afzel) harvested from the South Eastern Nigeria. Asian Journal of Chemical Sciences 2021;10:56-71. doi: 10.9734/ajocs/2021/v10i419103
Sudeep HV, Aman K, Jestin TV, Shyamprasad K. Aframomum melegueta seed extract with standardized content of 6-paradol reduces visceral fat and enhances energy expenditure in overweight adults - a randomized double-blind, placebo-controlled clinical study. Drug Des Devel Ther 2022;16:3777-3791. doi: 10.2147/DDDT.S367350
Latif M, Elkoraichi I, El Faqer O, Wahnou H, Mtairag EM, Oudghiri M, et al. Phytochemical analysis and immunomodulatory activities in vitro and in vivo of Aframomum melegueta K Schum seed extracts. Inflammopharmacology 2024;32:1621-31. doi: 10.1007/s10787-023-01422-7
Ogwu MC, Dunkwu-Okafor A, Omakor IA, Izah SC. Medicinal Spice, Aframomum melegueta: An Overview of the Phytochemical Constituents, Nutritional Characteristics, and Ethnomedicinal Values for Sustainability. In: Izah, S.C., Ogwu, M.C., Akram, M. (eds) Herbal Medicine Phytochemistry. Reference Series in Phytochemistry. Springer, Cham 2024;221-43. doi: 10.1007/978-3-031-43199-9_72
Moneva-Sakelarieva M, Kobakova Y, Konstantinov S, Momekov G, Ivanova S, Atanasova V, et al. The role of the transcription factor NF-kB in the pathogenesis of inflammation and carcinogenesis. Modulation capabilities. Pharmacia 2025;72:1-13. doi: 10.3897/pharmacia.72.e146759
Tao L, Ren X, Zhai W, Chen Z. Progress and prospects of non-canonical nf-κb signaling pathway in the regulation of liver diseases. Molecules 2022;27:4275. doi: 10.3390/molecules27134275
Zhang H, Sun SC. NF-κB in inflammation and renal diseases. Cell Biosci 2015;5:63. doi: 10.1186/s13578-015-0056-4
Hernandez-Barragan A, Medina-Avila Z, Montes-de-Oca-Angeles D, Lemus-Peña M, Hernandez-Santillan M, Martínez-Castillo M, et al. P-48 evaluation of IL-1β and IL-1RA in patients with chronic liver diseases. Annals of Hepatology 2023;28:100948. doi: 10.1016/j.aohep.2023.100948
Wijdan SA, Bokhari SMNA, Alvares J, Latif V. The role of interleukin-1 beta in inflammation and the potential of immune-targeted therapies. Pharmacological Research- Reports. 2025;3:100027. doi: 10.1016/j.prerep.2025.100027
Steiger S. Targeting IL-1 Receptor Signaling in AKI. Journal of the American Society of Nephrology 2023;34:1601-3. doi: 10.1681/ASN.0000000000000215
Amir M, Czaja MJ. Inflammasome-mediated inflammation and fibrosis: It is more than just the IL-1β. Hepatology 2018;67:479-81. doi: 10.1002/hep.29491
Anders HJ. Of Inflammasomes and Alarmins: IL-1β and IL-1α in Kidney Disease. Journal of the American Society of Nephrology 2016;27:2564-75. doi: 10.1681/ASN.2016020177
Muscolo A, Mariateresa O, Giulio T, Mariateresa R. Oxidative stress: the role of antioxidant phytochemicals in the prevention and treatment of diseases. Int J Mol Sci 2024;25:3264. doi: 10.3390/ijms25063264
Abdulla SK, Rashid BM, Salih KH, Mahmood NN, Marouf BH, Othman HH. Cardioprotective effect of zofenopril, thymoquinone and their combination in cyclophosphamide-induced cardiotoxicity in rats. Hum Exp Toxicol 2025;44:9603271251376594. doi: 10.1177/09603271251376594
Moronkeji A, Temidayo A, Benita A, Latifat O. Methanolic leaf extract of Vernonia amygdalina mitigates cadmium-induced oxidative stress in the liver and kidney of adult male Wistar rats. Egyptian Journal of Basic and Applied Sciences. 2024;11(1):469–478. doi: 10.1080/2314808X.2024.2360364
Adeniyi TD, Akinpelu M, Akinlami OO, Alaga FO, Adenika MM. Evaluation of the combined extract of Rauwolfia vomitoria and Aframomum melegueta on the kidney and liver of adult male Wistar rats. Sokoto J Med Lab Sci 2024;9:203-12. doi: 10.4314/sokjmls.v9i2.24
Ojo OA, Abolade O, Ogunlakin AD, Akintayo CO, Olukiran OS, Odesanmi OE, et al. Petiveria alliacea L. extract protects against streptozotocin-induced type-2 diabetes by modulating the cAMP/PKA/CREB/cFOS pathway. Phytomedicine Plus 2024;4:100596. doi: 10.1016/j.phyplu.2024.100596
Gebeya D, Afework M, Hagos S, Teklay A, Girmay M. Histopathological effects of cadmium on liver, kidneys and testis. Asian Journal of Science and Technology 2018; 09:8355-60.
Alharbi N, Elobeid M, Virk P. Protective effect of quercetin treatment against cadmium-induced oxidative stress in a male rat model. Pakistan Journal of Zoology 2019;51:2287-96.
Das SC, Al-Naemi HA. Cadmium toxicity: oxidative stress, inflammation and tissue injury. Occupational Diseases and Environmental Medicine 2019;07:144-63. doi: 10.4236/odem.2019.74012
Akinwumi KA, Gbadegesin MA, Aboyewa JA, Odunola OA. Attenuation of potassium dichromate and sodium arsenite toxicities by methanol extract of Rauvolfia vomitoria in mice. J Basic Clin Physiol Pharmacol 2020;33:255-64. -0037 doi: 10.1515/jbcpp-2020
Adeniyi T, Moronkeji A, Akinlami O, Kolawole MJ, Oloye J, Akogun I. Attenuation of cadmium toxicity by methanol extracts of rauvolfia vomitoria and aframomum melegueta leaves. Folia Medica Indonesiana 2024;60:94-102. doi: 10.20473/fmi.v60i2.55646
Oyinloye BE, Ajiboye BO, Ojo OA, Musa HM, Onikanni SA, Ojo AA. Ameliorative potential of Aframomum melegueta extract in cadmium- induced hepatic damage and oxidative stress in male Wistar rats. Journal of Applied Pharmaceutical Science 2016;6:94-9. doi: 10.7324/JAPS.2016.60714
Nwozo SO, Oyinloye BE. Hepatoprotective effect of aqueous extract of Aframomum melegueta on ethanol-induced toxicity in rats. Acta Biochimica Polonica 2011;58:355-358. doi: 10.18388/abp.2011_2246
Okoli CO, Akah PA, Nwafor S V, Ihemelandu UU, Amadife C. Anti-Inflammatory activity of seed extracts of aframomum melegueta. J Herbs Spices Med Plants 2007;13:11-21. doi: 10.1300/J044v13n01_02
Okeke BM, Adefegha SA, Oyeleye SI, Oboh G. Effects of combined crude alkaloid-rich extracts from alligator pepper (Aframomum melegueta) and bastered melegueta (Aframomum danielli) on the enzymes crucial to erectile dysfunction—in vitro. J Food Biochem 2018;42:1-11. doi: 10.1111/jfbc.12550
Oyeleke AA, Moronkeji A, Adeniyi T, Umeboro CP, Moronkeji AI, Omowaye B. Immuno-oxidative and histological evaluation of Vernonia amygdalina and Aframomum melegueta ethanolic leaf extracts in cadmium-induced cardiopulmonary toxicity in rats. FUOYE J Biomed Res 2024;1:140-7.
Ezejindu DN, Okafor IA, Anibeze CIP. Histological effects of Rauwolfia vomitoria extract on carbon tetrachloride induced hepatotoxicity in adult Wistar rats. Global Journal for Biology, Agriculture and Health Sciences 2013;2:73-7.
Abdou RM, El-Maadawy WH, Hassan M, El-Dine RS, Aboushousha T, El-Tanbouly ND, et al. Nephroprotective activity of Aframomum melegueta seeds extract against diclofenac-induced acute kidney injury: A mechanistic study. J Ethnopharmacol 2021;273:113939. doi: 10.1016/j.jep.2021.113939
El-Halawany AM, El Dine RS, El Sayed NS, Hattori M. Protective effect of Aframomum melegueta phenolics against CCl₄-induced rat hepatocytes damage; role of apoptosis and pro-inflammatory cytokines inhibition. Sci Rep 2014;4:5880. doi: 10.1038/srep05880
Tungmunnithum D, Thongboonyou A, Pholboon A, Yangsabai A. Flavonoids and other phenolic compounds from medicinal plants for pharmaceutical and medical aspects: an overview. Medicines (Basel) 2018;5:93. doi: 10.3390/medicines5030093
Chaachouay N. Synergy, additive effects, and antagonism of drugs with plant bioactive compounds. Drugs and Drug Candidate 2025;4:4. doi: 10.3390/ddc4010004
Adomefa NM, Essotolom B, Diallo A, Dougnon V, Mindédé A, Sanvee S, et al. Toxicological study of the aqueous extract of the stem bark of rauvolfia vomitoria (Apocynaceae). Asian Journal of Biological Sciences 2024;17:169-78, doi: 10.3923/ajbs.2024.169.178
Adegoke VO, Okpakpor EE, Uwaya D, Salawu OA, Ozolua RI. Toxicological evaluation of hydro-alcohol root extract of Rauwolfia vomitoria Afzel (Apocynaceae). Tropical Journal of Pharmaceutical Research 2024;23:1639-46. doi: 10.4314/tjpr.v23i10.7
Adefegha SA, Oboh G, Adefegha OM, Henle T. Alligator pepper/Grain of Paradise (Aframomum melegueta) modulates Angiotensin-I converting enzyme activity, lipid profile and oxidative imbalances in a rat model of hypercholesterolemia. Pathophysiology. 2016;23:191-202. doi: 10.1016/j.pathophys.2016.05.005
Kadiri HE, Apiamu A. Aframomum melegueta: a stimulator of liver function enzymes and a down-regulator of cyanide-mediated oxidative injuries in rats. Science World Journal 2022;17:375-9.
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