Main Article Content
Abstract
Highlights:
1. This study provides insight into the detrimental effect of cadmium exposure on mammalian cells using a murine model.
2. The co-administration of Rauvolfia vomitoria and Aframomum melegueta leaf extracts is more effective in ameliorating cadmium-induced toxicity than a single administration of each plant extract.
3. The co-administration of Rauvolfia vomitoria and Aframomum melegueta plant extracts can upregulate the expression of IL-10 and reverse the derangements in the TNF-α, IL-6, SOD, and GPX levels.
Abstract
Cadmium has long been known to be an environmental pollutant that can harm human health, with toxicity majorly affecting the kidneys and liver. This study aimed to investigate the mitigating potential of methanol extracts of Rauvolfia vomitoria and Aframomum melegueta leaves in cadmium-induced liver toxicity. Twenty-five male adult Wistar rats, averagely weighing 200 g, were randomly allocated into five groups, each comprising five rats. Group 1 was unexposed to any substances and only received distilled water. Group 2 was given cadmium at a standard dose of 12 mg/kg bw. Groups 3, 4, and 5 received 12 mg/kg bw of cadmium, and each group was treated with 200 mg/kg bw of Rauvolfia vomitoria leaf extract, Aframomum melegueta leaf extract, and a combination of both extracts, respectively. After 28 days, the animals were euthanized to obtain their livers, which were then excised and processed for histopathological, mRNA expression, and biochemical analyses. A one-way analysis of variance (ANOVA) was used to analyze the data, and Duncan multiple tests were employed to compare the categorical variables (p<0.05). The results revealed elevated levels of interleukin 10 (IL-10) in the rats treated with Rauvolfia vomitoria and Aframomum melegueta extracts when compared to Group 2. On the other hand, the treatment groups exhibited a significant decrease in tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) levels, along with significantly elevated levels of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Group 5 showed a normal liver histoarchitecture similar to Group 1, reversing the histopathological abnormalities shown in Group 2. In conclusion, the co-administrative treatment using Rauvolfia vomitoria and Aframomum melegueta extracts reversed the cadmium-induced toxicity better than using each plant extract individually. This further suggests that Rauvolfia vomitoria and Aframomum melegueta leaf methanol extracts may ameliorate the effects of cadmium-induced toxicity, including reducing oxidative stress and fortifying the anti-oxidant system.
Keywords
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References
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References
Abdou RM, El-Maadawy WH, Hassan M, et al (2021). Nephroprotective activity of Aframomum melegueta seeds extract against diclofenac-induced acute kidney injury: A mechanistic study. Journal of Ethnopharmacology 273, 1-13. doi: 10.1016/j.jep.2021.113939.
Abu-El-Zahab HSH, Hamza RZ, Montaser MM, et al (2019). Antioxidant, antiapoptotic, anti genotoxic, and hepatic ameliorative effects of L-carnitine and selenium on cadmium-induced hepatotoxicity and alterations in liver cell structure in male mice. Ecotoxicology and Environmental Safety 173, 419–428. doi: 10.1016/j.ecoenv.2019. 02.041.
Adeniyi TD, Moronkeji A, Ekundina VO (2023). Histological evaluation of the liver, kidney, and testes of adult male Wistar rats exposed to heavy metals-contaminated waterways. Medical Laboratory Journal 17, 1–8. doi: 10.2925/mlj.17. 54.
Adigun NS, Oladiji AT, Ajiboye TO (2016). Antioxidant and anti-hyperlipidemic activity of hydroethanolic seed extract of Aframomum melegueta K. Schum in Triton X-100 induced hyperlipidemic rats. South African Journal of Botany 105, 324–332. doi: 10.1016/j.sajb.2016. 03.015.
Agim C, Nosiri C, Chukwuma A, et al (2017). Evaluation of the phytochemical and GC-MS analysis of the aqueous seed extract of Aframomum melegueta. Journal of Pharmacognosy and Phytochemistry. Available at: https://www.phytojournal.com/archives/2017.v6.i2.1136/evaluation-of-the-phytochemical-and-gc-ms-analysis-of-the-aqueous-seed-extract-of-aframomum-melegueta.
Akindele AJ, Sowemimo A, Agunbiade FO, et al (2022). Bioprospecting for anti-COVID-19 interventions from African medicinal plants: A review. Natural Product Communications 17, 1-42. doi: 10.1177/1934578X221096968.
Akinpelu M, Gamade SM, Akinbo F, et al (2023). Histopathological and biochemical effect of vitamin C and D on phosphine-induced hepatotoxicity in wistar rats. Asian Journal of Dental and Health Sciences 3, 18–22. doi: 10.22270/ajdhs.v3i2.40.
Akinwumi KA, Gbadegesin MA, Aboyewa JA, et al (2022). Attenuation of potassium dichromate and sodium arsenite toxicities by methanol extract of Rauvolfia vomitoria in mice. Journal of Basic and Clinical Physiology and Pharmacology 33, 255–264. doi: 10.1515/jbcpp-2020-0037.
Andjelkovic M, Buha Djordjevic A, Antonijevic E, et al (2019). Toxic effect of acute cadmium and lead exposure in rat blood, liver, and kidney. International Journal of Environmental Research and Public Health 16, 274. doi: 10.3390/ijerph 16020274.
Anyanwu B, Ezejiofor A, Igweze Z, et al (2018). Heavy metal mixture exposure and effects in developing nations: An update. Toxics 6, 65. doi: 10.3390/toxics6040065.
Arhoghro EM, Sule OJ (2017). Ethanolic root extracts of rauwolfia vomitoria ameliorates reproductive toxicity and oxidative stress induced by aluminium chloride in rats. World Journal of Pharmacy and Pharmaceutical Sciences 1863–1874. doi: 10.20959/wjpps201704-8405.
Arroyo VS, Flores KM, Ortiz LB, et al (2013). Liver and Cadmium Toxicity. Journal of Drug Metabolism & Toxicology. doi: 10.4172/2157-7609.S5-001.
Ataba E, Katawa G, Toudji GA, et al (2020). Toxicity, chemical composition, anti-inflammatory and antioxidant activities of plants used for the treatment of helminth infections in the Kara and Central region of Togo. Journal of Applied Biosciences 156, 16114–16131. doi: 10.35759/JABs.156.5.
Bare Y, Marhendra A, Sasase T, et al (2018). Differential expression of IL-10 gene and protein in target tissues of Rattus norvegicus strain wistar model type 2 diabetes mellitus (T2DM). Acta Informatica Medica 26, 87. doi: 10.5455/aim. 2018.26.87-92.
Bisong S, Brown R, Osim E (2011). Comparative effects of Rauwolfia vomitoria and Chlorpromazine on social behaviour and pain. North American Journal of Medical Sciences 3, 48. doi: 10.4297/najms.2011.348.
Chinaka O. N, Linus K. E, Julius O. O, et al (2014). Hepatotoxicity of methanol seed extract of Aframomum melegueta [Roscoe] K. Schum. (grains of paradise) in sprague-dawley rats. American Journal of Biomedical Research 2, 61–66. doi: 10.12691/ajbr-2-4-1.
Ekong M, Ekpene U, Thompson F, et al (2015a). Effects of co-treatment of Rauwolfia vomitoria and Gongronema latifolium on neurobehaviour and the neurohistology of the cerebral cortex in mice. Internet Journal of Medical Update - EJOURNAL 10, 3. doi: 10.4314/ijmu.v10i1.2.
Ekong MB, Peter AI, Ekpene UU (2015b). Co-administration of Rauwolfia vomitoria with Gongronema latifolium or Vernonia amygdalina on spatial learning, memory, and some bio-molecules. Asian Journal of Medical Sciences 7, 82–87. doi: 10.3126/ajms.v7i1.11156.
El-Boshy ME, Risha EF, Abdelhamid FM, et al (2015). Protective effects of selenium against cadmium induced hematological disturbances, immunosuppressive, oxidative stress and hepatorenal damage in rats. Journal of Trace Elements in Medicine and Biology 29, 104–110. doi: 10.1016/j.jtemb.2014.05.009.
Ezejindu D., Okafor IA, Anibeze CIP, et al (2013a). The effects of Rauwolfia vomitoria extract on the liver enzymes of carbon tetrachloride-induced hepatotoxicity in adult wistar rats. Journal of Pharmacy and Biological Sciences (IOSR-JPBS) 7, 18–22. Available at: https://www.iosrj ournals.org/iosr-jpbs/papers/Vol7-issue2/D07218 22.pdf.
Ezejindu D, Asomugha L, Ukoha U (2013b). Hepatoprotective effects of Rauwolfia vomitoria extract on the liver of aduit wistar rats. International Journal of Pharmacological Research 3, 71–73. doi: 10.7439/IJPR.V3I4.59.
Fatima G, Raza AM, Hadi N, et al (2019). Cadmium in human diseases: It's more than just a mere metal. Indian Journal of Clinical Biochemistry 34, 371–378. doi: 10.1007/s12291-019-00839-8.
Fillatreau S, O'Garra A (2014). Interleukin-10 in health and diseaseed. Fillatreau S & O'Garra A. Springer Berlin Heidelberg, Berlin, Heidelberg. Available at: https://link.springer.com/10.1007 /978-3-662-43492-5.
Ilic NM, Dey M, Poulev AA, et al (2014). Anti-inflammatory activity of grains of paradise ( Aframomum melegueta schum) extract. Journal of Agricultural and Food Chemistry 62, 10452-10457. doi: 10.1021/jf5026086.
Jin T, Yin Q (2019). Structural immunology. Springer Singapore. Available at: https://link.springer.com/book/10.1007/978-981-13-9367-9.
KwaÅ›niak K, Czarnik-KwaÅ›niak J, Maziarz A, et al (2019). Scientific reports concerning the impact of interleukin 4, interleukin 10 and transforming growth factor on cancer cells. Central European Journal of Immunology 44, 190–200. doi: 10.5114/ceji.2018.76273.
Laamech J, El-Hilaly J, Fetoui H, et al (2017). Berberis vulgaris L. effects on oxidative stress and liver injury in lead-intoxicated mice. Journal of Complementary and Integrative Medicine. doi: 10.1515/jcim-2015-0079.
Moronkeji A, Eze IG, Bejide RA, et al (2018). Evaluation of herbal cocktail used in the treatment of malaria on liver tissue of adult Wistar rats. Journal of Medicinal Plants Research 12, 508–521. doi: 10.5897/JMPR2018.6661.
Moronkeji A, Frederick OA, Eze GI (2024). Histopathological and biochemical investigations of gasoline generator exhaust exposure in adult male Wistar rats. Sokoto Journal of Medical Laboratory Science (SJMLS). Available at: https://www.ajol.info/index.php/sokjmls/article/view/263177.
Moronkeji A, O.Akinbo F (2024). Genotoxic response and histological alterations in rat lungs exposed to gasoline generator exhaust. Sultan Qaboos University Journal for Science [SQUJS]. doi: 10.53539/squjs.vol29isspp15-27.
Niture S, Lin M, Qi Q, et al (2021). Role of autophagy in cadmium-induced hepatotoxicity and liver diseases ed. Orisakwe OE. Journal of Toxicology 2021, 1–14. doi: 10.1155/2021/95 64297.
Obike HI, Ezejindu DN, Chukwujekwu IE (2014). The effects of Aframomum melegueta aqueous extract on the kidneys of adult wistar rats. International Journal of Health Sciences & Research 4, 111-115. Available at: https://www.ijhsr.org/IJHSR_Vol.4_Issue.4_April2014/17.pdf.
Okon AM, Eluwa M, Iniodu CF, et al (2017). Comparing the adverse impact of ethanolic root bark and leaf extracts of Rauwofia vomitoria (apocynaceae) on cerebellar glycogen in adult wistar rats. Saudi Journal of Medical and Pharmaceutical Sciences 3, 941–946. doi: 10.36348/sjmps.2017.v03i09.001.
Oshomoh EO, Okolafor FI, Idu M (2015). Antimicrobial screening and the toxicity of the aqueous extract of the root of Zanthozylum zanthozyloides on haematology and the spleen of wistar rats. Journal of Medicine and Biomedical Research. Available at: https://www.semantic scholar.org/paper/Antimicrobial-screening-and-the-toxicity-of-the-of-OshomohOkolafor/47370cfb918883ca7f7a4e57b5a26e54133ad565.
Osuntokun OT, Oluduro A, Idowu T, et al (2017). Assessment of nephrotoxicity anti-inflammatory and antioxidant properties. Journal of Molecular Microbiology 1, 103. Available at: https://www.academia.edu/35028314/Assessment_of_Nephrotoxicity_Anti_Inflammatory_and_Antioxidant_Properties.
Oyeniran OH, Ademiluyi AO, Oboh G (2021). Phenolic constituents and inhibitory effects of the leaf of Rauvolfia vomitoria Afzel on free radicals, cholinergic and monoaminergic enzymes in rat's brain in vitro. Journal of Basic and Clinical Physiology and Pharmacology l 32, 987–994. doi: 10.1515/jbcpp-2020-0144.
Oyinloye B, Ajiboye B, Ojo O, et al (2016). Ameliorative potential of Aframomum melegueta extract in cadmium-induced hepatic damage and oxidative stress in male Wistar rats. Journal of Applied Pharmaceutical Science 94–99. doi: 10.7324/JAPS.2016.60714.
Rahimzadeh MR, Rahimzadeh MR, Kazemi S, et al (2017). Cadmium toxicity and treatment: An update. Caspian Journal of Internal Medicine 8, 135–145. doi: 10.22088/cjim.8.3.135.
Rojas JM, Avia M, Martín V, et al. (2017). IL-10: A multifunctional cytokine in viral infections. Journal of Immunology Research 2017, 1–14. doi: 10.1155/2017/6104054.
Saad B, Ghareeb B, Kmail A (2021). Metabolic and epigenetics action mechanisms of antiobesity medicinal plants and phytochemicals ed. Zarrelli A. Evidence-Based Complementary and Alternative Medicine, 1–19. doi: 10.1155/2021/9995903.
Sharma H, Rawal N, Mathew BB (2015). The characteristics, toxicity and effects of cadmium. International Journal of Nanotechnology and Nanoscience 3, 1–9. Available at: https://www.researchgate.net/publication/305778858_The_characteristics_toxicity_and_effects_of_cadmium.
SPSS Inc (2008). SPSS statistics for Windows, version 17.0. Chicago: SPSS Inc. Available at: https://www.ibm.com/support/pages/spss-modele r-170-now-available-download.
Verma R, Balakrishnan L, Sharma K, et al. (2016). A network map of Interleukin-10 signaling pathway. Journal of Cell Communication and Signaling 10, 61–67. doi: 10.1007/s12079-015-0302-x.