{"title":"Esculin mitigates nickel chloride-induced generation of ROS, hemoglobin oxidation, and alterations in redox status in human red blood cells","authors":"Monika Sharma, Fahim Halim Khan, Riaz Mahmood","doi":"10.1016/j.jtemb.2025.127626","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Nickel (Ni) is a heavy metal and an environmental pollutant that is harmful to humans because of its carcinogenicity and toxic effects on several tissues and organs. Due to their widespread use concerns have been raised about the potential adverse effects of Ni and its compounds on human health. Ni compounds induce oxidative stress in cells by modifying the redox equilibrium. This work studied the protective role of the plant antioxidant esculin (ES) against nickel chloride (NiCl<sub>2</sub>)-induced oxidative damage and cytotoxicity in isolated human red blood cells (RBC).</div></div><div><h3>Methods</h3><div>Human RBC were first incubated with varying concentrations of ES (0.25–1.0 mM) for 2 h at 37 °C, followed by addition of 0.5 mM NiCl<sub>2</sub> and further incubation for 24 h at 37 °C.</div></div><div><h3>Results</h3><div>Treatment of RBC with NiCl<sub>2</sub> alone increased the production of reactive oxygen species and significantly enhanced methemoglobin level, heme degradation, free iron release and hydrogen peroxide content. It also led to oxidation of cellular thiol groups, proteins and lipids. The glutathione content, total sulfhydryl groups, nitric oxide level and free amino groups were decreased. The activities of antioxidant, metabolic and plasma membrane enzymes were inhibited and the antioxidant capacity of RBC was lowered. However, pre-incubation of RBC with ES greatly mitigated the NiCl<sub>2</sub>-induced alterations in these parameters in an ES concentration-dependent manner. In all cases ES alone did not exhibit any significant toxic effect. This was confirmed by electron microscopic analysis of RBC. Treatment with NiCl<sub>2</sub> alone resulted in the conversion of biconcave discoidal RBC to echinocytes but this change in cell morphology was greatly prevented in the presence of ES. The ES alone treated RBC did not show altered cell morphology.</div></div><div><h3>Conclusion</h3><div>These results suggest that ES can be potentially used as a cytoprotectant against Ni-induced toxicity.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"88 ","pages":"Article 127626"},"PeriodicalIF":3.6000,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Trace Elements in Medicine and Biology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0946672X25000392","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Nickel (Ni) is a heavy metal and an environmental pollutant that is harmful to humans because of its carcinogenicity and toxic effects on several tissues and organs. Due to their widespread use concerns have been raised about the potential adverse effects of Ni and its compounds on human health. Ni compounds induce oxidative stress in cells by modifying the redox equilibrium. This work studied the protective role of the plant antioxidant esculin (ES) against nickel chloride (NiCl2)-induced oxidative damage and cytotoxicity in isolated human red blood cells (RBC).
Methods
Human RBC were first incubated with varying concentrations of ES (0.25–1.0 mM) for 2 h at 37 °C, followed by addition of 0.5 mM NiCl2 and further incubation for 24 h at 37 °C.
Results
Treatment of RBC with NiCl2 alone increased the production of reactive oxygen species and significantly enhanced methemoglobin level, heme degradation, free iron release and hydrogen peroxide content. It also led to oxidation of cellular thiol groups, proteins and lipids. The glutathione content, total sulfhydryl groups, nitric oxide level and free amino groups were decreased. The activities of antioxidant, metabolic and plasma membrane enzymes were inhibited and the antioxidant capacity of RBC was lowered. However, pre-incubation of RBC with ES greatly mitigated the NiCl2-induced alterations in these parameters in an ES concentration-dependent manner. In all cases ES alone did not exhibit any significant toxic effect. This was confirmed by electron microscopic analysis of RBC. Treatment with NiCl2 alone resulted in the conversion of biconcave discoidal RBC to echinocytes but this change in cell morphology was greatly prevented in the presence of ES. The ES alone treated RBC did not show altered cell morphology.
Conclusion
These results suggest that ES can be potentially used as a cytoprotectant against Ni-induced toxicity.
期刊介绍:
The journal provides the reader with a thorough description of theoretical and applied aspects of trace elements in medicine and biology and is devoted to the advancement of scientific knowledge about trace elements and trace element species. Trace elements play essential roles in the maintenance of physiological processes. During the last decades there has been a great deal of scientific investigation about the function and binding of trace elements. The Journal of Trace Elements in Medicine and Biology focuses on the description and dissemination of scientific results concerning the role of trace elements with respect to their mode of action in health and disease and nutritional importance. Progress in the knowledge of the biological role of trace elements depends, however, on advances in trace elements chemistry. Thus the Journal of Trace Elements in Medicine and Biology will include only those papers that base their results on proven analytical methods.
Also, we only publish those articles in which the quality assurance regarding the execution of experiments and achievement of results is guaranteed.