@article{MTMT:34587031,
	title = {Selenium and zinc supplementation mitigates metals-(loids) mixture- mediated cardiopulmonary toxicity via attenuation of antioxidant, anti-inflammatory and antiapoptotic mechanisms in female Sprague Dawley rats},
	url = {https://m2.mtmt.hu/api/publication/34587031},
	author = {Antia, Mfoniso and Ezejiofor, Anthonet N. and Orish, Chinna N. and Cirovic, Ana and Cirovic, Aleksandar and Orisakwe, Orish E.},
	doi = {10.1093/toxres/tfad119},
	journal-iso = {TOXICOL RES-UK},
	journal = {TOXICOLOGY RESEARCH},
	volume = {13},
	unique-id = {34587031},
	issn = {2045-452X},
	abstract = {This study evaluated the cardiopulmonary protective effects of essential elements (Zn and Se) against heavy metals mixture (HMM) exposure. Twenty five female Sprague Dawley albino rats, divided in to five groups: controls were orally treated only with distilled water; next, group 2 was exposed to HMM with the following concentrations: 20 mg/kg of Pb body weight, 0.40 mg/kg of Hg, 0.56 mg/kg of Mn, and 35 mg/kg of Al. Groups 3, 4 and 5 were exposed to HMM and co-treated with zinc chloride (ZnCl2; 0.80 mg/kg), sodium selenite (Na2SeO3;1.50 mg/kg) and both zinc chloride and sodium selenite, respectively. The experiment lasted for 60 days. Afterwards animals were sacrificed, and we conduced biochemical and histopathological examination of the heart and lungs. HMM only exposed animals had an increased levels of malondialdehyde (MDA) and nitric oxide (NO), increased IL-6 and TNF-alpha, attenuated SOD, GPx, CAT and GSH and caspase 3 in the heart and lungs. HMM affected NF-kB and Nrf2 in the heart muscle with histomorphological alterations. Zn and Se attenuated adverse effects of HMM exposure. Essential element supplementation ameliorated heavy metal cardiopulmonary intoxication in rats.Graphical AbstractSchematic approach to experimental design (used heavy metals mixture and duration of exposure), examined organs and main outcomes of this study.},
	keywords = {LUNGS; HEART; Heavy metals; Metalloids; Essential trace elements; oxido-inflammatory},
	year = {2024},
	eissn = {2045-4538}
}

@article{MTMT:34244456,
	title = {Selenium and zinc alleviate quaternary metal mixture -induced neurotoxicity in rats by inhibiting oxidative damage and modulating the expressions of NF-kB and Nrf2/Hmox-1 pathway},
	url = {https://m2.mtmt.hu/api/publication/34244456},
	author = {Dike, Chinyere and Orish, Chinna N. and Ezejiofor, Anthonet N. and Cirovic, Ana and Cirovic, Aleksandar and Babatunde, Bolaji and Sikoki, Francis and Orisakwe, Orish E.},
	doi = {10.1016/j.ibneur.2023.06.003},
	journal-iso = {IBRO NEUROSCI REP},
	journal = {IBRO NEUROSCIENCE REPORTS},
	volume = {15},
	unique-id = {34244456},
	abstract = {Background: This study evaluated the potential protective effects of Zn and Se in the cerebellum and cerebral cortex, two fundamentally important brain regions, in albino rats that were exposed to heavy metals mixture (Al, Pb, Hg and Mn). Methods: Animals were divided into five groups of seven animals per group with following patterns of exposure, controls group 1 were orally treated with deionized water for 60 days; group 2 was exposed to heavy metal mixture (HMM) with following concentrations (20 mg & BULL;kg  1 of Pb body weight; 0.40 mg & BULL;kg  1 of Hg; 0.56 mg & BULL;kg  1 of Mn; and 35 mg & BULL;kg  1; of Al), while groups 3,4 and 5 were exposed to HMM and orally co-treated with zinc chloride (ZnCl2; 0.80 mg/kg), sodium selenite (Na2SeO3;1.50 mg/kg) and zinc chloride plus sodium selenite (ZnCl0.2 + Na2SeO3) respectively. Results: Exposure to HMM depressed cellular antioxidant apparatus, induced generation of lipid peroxidation markers (Malondialdehyde and NO), downregulated expression of transcription factors (Nrf2, and NF-kB) and upregulated Caspase 3 levels. HMM potentiated acetylcholinesterase activity and induced moderate histopathological alterations. Nevertheless, Zn, Se and in particular Zn + Se had recovering effects on all mentioned hazardous effects produced by HMM exposure in the cerebral cortex and cerebellum. Conclusions: Selenium and zinc exert neuroprotection via Nrf2/NF-kB signaling pathways against quaternary heavy metal mixture-induced impairments in albino Sprague Dawley rats.},
	keywords = {Cerebral Cortex; CEREBELLUM; Heavy metals mixture; Beneficial effects of Zn and Se},
	year = {2023},
	eissn = {2667-2421},
	pages = {57-67},
	orcid-numbers = {Cirovic, Ana/0009-0004-9085-5308; Cirovic, Aleksandar/0000-0001-6010-9559}
}

@article{MTMT:34587030,
	title = {Selenium and zinc protect against heavy metal mixture-induced, olfactory bulb and hippocampal damage by augmenting antioxidant capacity and activation of Nrf2-Hmox-1 signaling in male rats},
	url = {https://m2.mtmt.hu/api/publication/34587030},
	author = {Ikpeama, Evelyn U. and Orish, Chinna N. and Ezejiofor, Anthonet N. and Cirovic, Ana and Cirovic, Aleksandar and Nwaogazie, Ify L. and Orisakwe, Orish E.},
	doi = {10.1080/00207454.2023.2295227},
	journal-iso = {INT J NEUROSCI},
	journal = {INTERNATIONAL JOURNAL OF NEUROSCIENCE},
	unique-id = {34587030},
	issn = {0020-7454},
	abstract = {Purpose/aim of the studyHeavy metals and metalloids have been implicated in neurodenerative diseases. Present study has evaluated the potential protective effects of Se and Zn on heavy metals and metalloids mixture-induced (Cd, Pb, Hg and As) toxicity in the hippocampus and olfactory bulb in male rats.Materials and methodsFive groups of Wistar rats were randomly divided in to: controls, toxic metals mixture (TMM) exposed rats (PbCl2, 20 mg center dot kg-1; CdCl2, 1.61 mg center dot kg-1; HgCl2, 0.40 mg center dot kg-1 and NaAsO3, 10 mg center dot kg-1)), TMM + Zn, TMM + Se and TMM-+Zn + Se groups and were orally treated for 60 days.ResultsWe found that in hippocampus and olfactory bulb, TMM generated increased lipid peroxidation and diminished antioxidant capacity. These adverse effects induced by TMM were alleviated by Zn and Se co-treatment; moreover, essential trace elements (Zn and Se) decreased activity of acetylcholinesterase, reduced Cd, Pb, Hg and As bioaccumulation in hippocampus and olfactory bulb and decreased levels of TNF-alpha in the hippocampus. TMM treated rats had lower levels of Hmox-1 (hippocampus), higher levels of Nrf2 (olfactory bulb and hippocampus) and NF-kB (olfactory bulb). TMM treated rats showed significantly highest time in locating the escape hole. Histopathological examination revealed hypertrophied granule cells in OB of TMM exposed rats.ConclusionZn and Se supplementation can reverse quaternary mixture-induced (Cd, Pb, Hg and As) toxicity in hippocampus and OB in male albino rats.},
	keywords = {Lipid Peroxidation; ACETYLCHOLINE; Hippocampus (HIP) and olfactory bulb (OB)},
	year = {2023},
	eissn = {1563-5279}
}

@article{MTMT:34244457,
	title = {Zinc and selenium attenuate quaternary heavy metal mixture-induced testicular damage via amplification of the antioxidant system, reduction in metal accumulation, inflammatory and apoptotic biomarkers},
	url = {https://m2.mtmt.hu/api/publication/34244457},
	author = {Ozoani, Harrison and Ezejiofor, Anthonet N. and Okolo, Kenneth O. and Orish, Chinna N. and Cirovic, Ana and Cirovic, Aleksandar and Orisakwe, Orish E.},
	doi = {10.1007/s43188-023-00187-z},
	journal-iso = {Toxic Res},
	journal = {TOXICOLOGICAL RESEARCH},
	volume = {39},
	unique-id = {34244457},
	issn = {1976-8257},
	abstract = {Heavy metals (HMs) such as cadmium (Cd), lead (Pb), arsenic (As), and mercury (Hg) are highly toxic elements. They are often found together in nature as a heavy metal mixture (HMM) and are known to contribute to subfertility/infertility as environmental pollutants. This study aims to evaluate the potential benefits of treating HMM-induced testicular pathophysiology with zinc (Zn) and/or selenium (Se). Six-week-old male Sprague Dawley rats were grouped into 5 (n = 7). The control group received deionized water, while the other groups were treated with PbCl2 (20 mg kg(-1)), CdCl2 (1.61 mg kg(-1)), HgCl2 (0.40 mg kg(-1)), and Na2AsO3 (10 mg kg(-1)) in deionized water for 60 days. Additionally, groups III to V received Zn, Se, and Zn/Se, respectively, for 60 days. The study evaluated testis weight, metal accumulation, sperm analysis, FSH, LH, testosterone, prolactin, oxidative stress, antioxidants, pro-inflammatory and apoptotic markers, and presented structural changes in the testis as micrographs. HMM caused a significant increase in testis weight, metal accumulation, prolactin, oxidative stress, and pro-inflammatory and apoptotic markers, while significantly decreasing semen analysis, FSH, LH, and testosterone. Histology showed decreased spermatogenesis and spermiogenesis, as evidenced by the structure of the germ cells and spermatids. However, Zn, Se, or both ameliorated and reversed some of the observed damages. This study provides further evidence for the mitigative potential of Zn, Se, or both in reversing the damage inflicted by HMM in the testis, and as a countermeasure towards improving HM-induced decrease in public health fecundity.},
	keywords = {Arsenic; Heavy metals; testis; essential elements; ROS},
	year = {2023},
	eissn = {2234-2753},
	pages = {497-515},
	orcid-numbers = {Cirovic, Ana/0009-0004-9085-5308; Cirovic, Aleksandar/0000-0001-6010-9559}
}

@article{MTMT:33851041,
	title = {Banana peel ameliorated hepato-renal damage and exerted anti-inflammatory and anti-apoptotic effects in metal mixture mediated hepatic nephropathy by activation of Nrf2/ Hmox-1 and inhibition of Nfkb pathway},
	url = {https://m2.mtmt.hu/api/publication/33851041},
	author = {Eddie-Amadi, Boma F. and Ezejiofor, Anthonet N. and Orish, Chinna N. and Rovira, Joaquim and Allison, Theodore A. and Orisakwe, Orish E.},
	doi = {10.1016/j.fct.2022.113471},
	journal-iso = {FOOD CHEM TOXICOL},
	journal = {FOOD AND CHEMICAL TOXICOLOGY},
	volume = {170},
	unique-id = {33851041},
	issn = {0278-6915},
	abstract = {This study evaluated the protective role of banana peel extract (BP) on heavy metal mixture (HMM) mediated hepatorenal toxicity using a rat model. Twenty-five female Wistar albino rats were weight-matched and divided into five groups of five female rats each. Group 1(control) received deionized water only. Group 2 received HMM only (20 mg kg -1 of Pb, 0.40 mg kg -1 of Hg, 0.56 mg kg-1 of Mn and 35 mg kg-1 of Al). Groups 3, 4 and 5 were co-administered with the same metal mixture with BP at 200, 400 and 800 mg kg -1, respectively. Treatments were through oral gavage for 60 days; animals were sacrificed pentobarbital anesthesia and liver and kidney harvested for test. Thereafter, metal levels, malondialdehyde (MDA) and nitric oxide (NO), catalase (CAT), glutathione content (GSH), superoxide dismutase (SOD), and glutathione peroxidase (GPx), interlukin-6 (IL-6) and tumor necrosis alpha (Tnf-alpha), caspase-3 (Cas-3), Nuclear factor kappa B (Nfkb), Nuclear factor erythroid 2 -related factor 2 (Nrf2) and heme oxygenase-1 (Hmox-1) were assayed. HMM group presented higher levels of metal, IL-6 and Tnf-alpha, MDA, NO, Nfkb and Hmox-1 in HMM group which were significantly reduced by BP. BP was protective against metal mixture induced histopathological distortions. HMM exposure significantly dis-torted hepatorenal functions and BP treatment reduced metal bioavailability and abrogated most of these alterations.},
	keywords = {Inflammation; Programmed cell death; Banana; Oxidative stress; Metal mixture toxicity; Hepatorenal functions},
	year = {2022},
	eissn = {1873-6351}
}

@article{MTMT:33851042,
	title = {Zinc and selenium mitigated heavy metals mixture (Pb, Al, Hg and Mn) mediated hepatic-nephropathy via modulation of oxido-inflammatory status and NF-kB signaling in female albino rats},
	url = {https://m2.mtmt.hu/api/publication/33851042},
	author = {Eddie-Amadi, Boma F. and Ezejiofor, Anthonet N. and Orish, Chinna N. and Orisakwe, Orish E.},
	doi = {10.1016/j.tox.2022.153350},
	journal-iso = {TOXICOLOGY},
	journal = {TOXICOLOGY},
	volume = {481},
	unique-id = {33851042},
	issn = {0300-483X},
	abstract = {This study evaluated the protective role o of zinc and selenium on heavy metal mixture (HMM) induced hepatic-nephropathy. Twenty-five female Wistar albino rats were weight-matched and divided into five groups of five female rats each. Group 1(control) received deionized water only. Group 2 received heavy metal mixture HMM (20 mg.kg(-1) of Pb, 0.40 mg.kg(-1) of Hg, 0.56 mg.kg(-1) of Mn and 35 mg.kg(-1) of Al). Groups 3, 4 and 5 were co-administered with metal mixtures and Zn, Se and Zn + Se respectively. Treatments were through oral gavage for 60 days; animals were sacrificed under pentobarbital and liver and kidney harvested for tests. Zn, Se and Zn + Se reduced metal accumulation in the liver and kidney. HMM exposure caused non-significant increase in AST, ALP, ALT and TP, but significant increase in IL-6 and TNF -alpha, Nf-kB, Hmox-1, Nfr2, MDA and NO when compared to the control. Essential trace elements significantly decreased IL-6 and TNF -alpha, Nf-kB, Hmox-1and Nfr2 in comparison to HMM only group. Treatment with Zn, Se and Zn + Se significantly reversed the HHM mediated decreased SOD levels. HMM triggered degenerative changes in the central vein, showed vacuolations with connective tissues fragmentation and lymphocytes infiltration were reversed by essential trace elements. Essential trace elements supplementation is protective against HMM mediated hepato-renal impairment.},
	keywords = {essential metals; Heavy metal mixture, antioxidants; Anti-inflammatory, anti-apoptotic; Liver, kidney},
	year = {2022},
	eissn = {1879-3185}
}

@article{MTMT:31361271,
	title = {Low‐dose heavy metal mixture (lead, cadmium and mercury)‐induced testicular injury and protective effect of zinc and Costus afer in wistar albino rats},
	url = {https://m2.mtmt.hu/api/publication/31361271},
	author = {Anyanwu, Brilliance O. and Ezejiofor, Anthonet N. and Nwaogazie, Ify L. and Akaranta, Onyewuchi and Orisakwe, Orish E.},
	doi = {10.1111/and.13697},
	journal-iso = {ANDROLOGIA},
	journal = {ANDROLOGIA},
	volume = {1},
	unique-id = {31361271},
	issn = {0303-4569},
	year = {2020},
	eissn = {1439-0271},
	orcid-numbers = {Orisakwe, Orish E./0000-0002-5806-9858}
}

@article{MTMT:31408769,
	title = {Neuroprotective effect of Costus afer on low dose heavy metal mixture (lead, cadmium and mercury) induced neurotoxicity via antioxidant, anti-inflammatory activities},
	url = {https://m2.mtmt.hu/api/publication/31408769},
	author = {Anyanwu, Brilliance O. and Orish, Chinna N. and Ezejiofor, Anthonet N. and Nwaogazie, Ify L. and Orisakwe, Orish E.},
	doi = {10.1016/j.toxrep.2020.08.008},
	journal-iso = {TOXICOL REPORTS},
	journal = {TOXICOLOGY REPORTS},
	unique-id = {31408769},
	year = {2020},
	eissn = {2214-7500}
}

@article{MTMT:31726315,
	title = {Protective Effect of Costus afer Aqueous Leaf Extract (CALE) on Low-Dose Heavy Metal Mixture-Induced Alterations in Serum Lipid Profile and Hematological Parameters of Male Wistar Albino Ratsa},
	url = {https://m2.mtmt.hu/api/publication/31726315},
	author = {Anyanwu, Brilliance O. and Orish, Chinna N. and Ezejiofor, Anthonet N. and Nwaogazie, Ify L. and Orisakwe, Orish E.},
	doi = {10.1155/2020/8850264},
	journal-iso = {JOURNAL OF TOXICOLOGY},
	journal = {JOURNAL OF TOXICOLOGY},
	volume = {2020},
	unique-id = {31726315},
	issn = {1687-8191},
	abstract = {The present work investigated the protective effects ofCostus aferKer Gawl. aqueous leaf extract (CALE) on lipid profile and hematological changes induced by exposure to low-dose heavy metal mixture in male albino rats. The experimental animals were divided into six weight matched groups. The normal (group 1) and toxic (group 2) controls received deionized water and metal mixture (20 mg/kg PbCl2, 1.61 mg/kg CdCl2, and 0.40 mg/kg HgCl2), respectively. Test rats in groups 3, 4, and 5 were treated with metal mixture and CALE (750, 1500, and 2250 mg/kg, respectively), and group 6 received metal mixture and ZnCl2. All treatments were administered through oral gavage for 12 weeks. LDHMM caused a marked increase (p<0.05) in cholesterol, triglyceride, low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) levels and a decrease in high-density lipoprotein (HDL), percentage body weight gain, and feed and fluid intake. Also, a significant decrease in RBC, Hb, and PCV, a significant increase in WBC, and no significant increase in platelet PLT were observed in the metal mixture-treated group. But in CALE treated groups, their levels were found to attain almost normal values as found in normal control which is also similar to the zinc-treated group.Costus afermay hold a promise in improving lipid profile and hemodynamic picture in cardiovascular diseases.},
	year = {2020}
}

@article{MTMT:26164611,
	title = {Einfluss toxischer Metalle auf die Krebsentstehung},
	url = {https://m2.mtmt.hu/api/publication/26164611},
	author = {Jennrich, P and Schulte-Uebbing, C},
	doi = {10.1055/s-0042-103521},
	journal-iso = {DEUTSCHE ZEI ONKOL},
	journal = {DEUTSCHE ZEITSCHRIFT FUR ONKOLOGIE},
	volume = {48},
	unique-id = {26164611},
	issn = {1617-5891},
	year = {2016},
	pages = {14-24}
}

@article{MTMT:30611360,
	title = {The Influence of Arsenic, Lead, and Mercury on the Development of Cardiovascular Diseases},
	url = {https://m2.mtmt.hu/api/publication/30611360},
	author = {Jennrich, Peter},
	doi = {10.5402/2013/234034},
	journal-iso = {ISRN Hypertension},
	journal = {ISRN Hypertension},
	volume = {2013},
	unique-id = {30611360},
	year = {2013},
	eissn = {2090-8709},
	pages = {1-15}
}

@article{MTMT:21696269,
	title = {Lead affects apoptosis and related gene XIAP and smac expression in the hippocampus of developing rats},
	url = {https://m2.mtmt.hu/api/publication/21696269},
	author = {Liu, J and Han, D and Li, Y and Zheng, L and Gu, C and Piao, Z and Au, W W and Xu, X and Huo, X},
	doi = {10.1007/s11064-009-0083-9},
	journal-iso = {NEUROCHEM RES},
	journal = {NEUROCHEMICAL RESEARCH},
	volume = {35},
	unique-id = {21696269},
	issn = {0364-3190},
	year = {2010},
	eissn = {1573-6903},
	pages = {473-479}
}

@article{MTMT:20887326,
	title = {Elevated blood lead levels in a riverside population in the Brazilian amazon.},
	url = {https://m2.mtmt.hu/api/publication/20887326},
	author = {Barbosa, F and Fillion, M and Lemire, M and Sousa, Passos C J and Lisboa, Rodrigues J and Philibert, A and Guimarães, J -R and Mergler, D},
	doi = {10.1016/j.envres.2009.03.005},
	journal-iso = {ENVIRON RES},
	journal = {ENVIRONMENTAL RESEARCH},
	volume = {109},
	unique-id = {20887326},
	issn = {0013-9351},
	year = {2009},
	eissn = {1096-0953},
	pages = {594-599}
}

@article{MTMT:20887334,
	title = {Lead and Cadmium Synergistically Enhance the Expression of Divalent Metal Transporter 1 Protein in Central nervous System of Developing Rats.},
	url = {https://m2.mtmt.hu/api/publication/20887334},
	author = {Gu, CW and Chen, SJ and Xu, XJ and Zheng, L and Li, Y and Wu, K and Liu, J and Qi, Z and Han, D and Chen, G and Huo, X},
	doi = {10.1007/s11064-008-9891-6},
	journal-iso = {NEUROCHEM RES},
	journal = {NEUROCHEMICAL RESEARCH},
	volume = {34},
	unique-id = {20887334},
	issn = {0364-3190},
	year = {2009},
	eissn = {1573-6903},
	pages = {1150-1156}
}