Pub Date : 2024-07-27DOI: 10.1007/s00210-024-03317-y
Lucia Gerke, Roland Seifert
Traditional and alternative medicines are widely used around the world and include for example herbal medicine, Ayurveda, traditional Chinese medicine, and indigenous therapies. Due to the long history and the mostly natural origin of traditional remedies, it is often assumed that they are harmless, but in recent decades more and more case reports have been published in which traditional medicine has caused metal poisoning. This paper provides an analysis of published cases in which patients have suffered metal poisoning due to traditional or alternative medicines. A systematic literature search was performed on PubMed, whereby 210 patient cases from a total of 102 case reports and 30 case series were identified and then analyzed about various aspects. Most of the traditional medicines involved come from Asia and are mainly contaminated with lead and arsenic. The analyzed patient cases show a high degree of heterogeneity with regard to age, sex, intake reason, symptoms, and severity of intoxication. The metal intoxication itself and the cause of the poisoning often remained unrecognized for a long time, which resulted in many patients undergoing unnecessary diagnostic methods and ineffective therapeutic approaches before the correct diagnosis was made. The evaluation of the available patient cases revealed a higher sensitivity to metal poisoning in children compared to adults and a higher sensitivity in men compared to women. Anemia and basophilic stippling were frequently observed and became more common as the metal content in the blood increased. Hopefully, this paper raises awareness of the potential dangers of traditional and alternative medicines, both from the patient’s and the doctor’s perspective, so that in case of intoxication, treatment can be initiated quickly using the correct diagnostic methods. As ingested metals do not only circulate in the blood but also accumulate in soft tissues and bones, long-term monitoring is necessary to ensure that patients make a full recovery. Doctors should be aware that, in contrast to common belief, men are more sensitive to this type of intoxication than women, necessitating particular attention for diagnosis and treatment.
{"title":"Lead and arsenic intoxications by traditional and alternative medicine: men are more sensitive than women","authors":"Lucia Gerke, Roland Seifert","doi":"10.1007/s00210-024-03317-y","DOIUrl":"https://doi.org/10.1007/s00210-024-03317-y","url":null,"abstract":"<p>Traditional and alternative medicines are widely used around the world and include for example herbal medicine, Ayurveda, traditional Chinese medicine, and indigenous therapies. Due to the long history and the mostly natural origin of traditional remedies, it is often assumed that they are harmless, but in recent decades more and more case reports have been published in which traditional medicine has caused metal poisoning. This paper provides an analysis of published cases in which patients have suffered metal poisoning due to traditional or alternative medicines. A systematic literature search was performed on PubMed, whereby 210 patient cases from a total of 102 case reports and 30 case series were identified and then analyzed about various aspects. Most of the traditional medicines involved come from Asia and are mainly contaminated with lead and arsenic. The analyzed patient cases show a high degree of heterogeneity with regard to age, sex, intake reason, symptoms, and severity of intoxication. The metal intoxication itself and the cause of the poisoning often remained unrecognized for a long time, which resulted in many patients undergoing unnecessary diagnostic methods and ineffective therapeutic approaches before the correct diagnosis was made. The evaluation of the available patient cases revealed a higher sensitivity to metal poisoning in children compared to adults and a higher sensitivity in men compared to women. Anemia and basophilic stippling were frequently observed and became more common as the metal content in the blood increased. Hopefully, this paper raises awareness of the potential dangers of traditional and alternative medicines, both from the patient’s and the doctor’s perspective, so that in case of intoxication, treatment can be initiated quickly using the correct diagnostic methods. As ingested metals do not only circulate in the blood but also accumulate in soft tissues and bones, long-term monitoring is necessary to ensure that patients make a full recovery. Doctors should be aware that, in contrast to common belief, men are more sensitive to this type of intoxication than women, necessitating particular attention for diagnosis and treatment.</p>","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141784820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-27DOI: 10.1007/s00210-024-03316-z
Ahmad Karzoon, Mükerrem Betül Yerer, Ahmet Cumaoğlu
Accumulating evidence suggests that sodium–glucose cotransporter 2 (SGLT2) inhibitors may be effective at eliminating tumor cells. While empagliflozin exhibits nearly the highest selectivity for SGLT2 over SGLT1, its specific impact alone and in combination with tamoxifen remains largely unexplored in estrogen receptor α-positive (ERα +) breast cancer. This study investigated the anticancer effects of empagliflozin and its potential synergy with tamoxifen in MCF-7 breast cancer cells. The individual and combined cytotoxic effects of empagliflozin and tamoxifen were assessed using the xCELLigence system. The activities of AMP-activated protein kinase α (AMPKα), p38 mitogen-activated protein kinase (p38 MAPKα), p70-S6 kinase 1 (p70S6K1), and protein kinase B (Akt) were assessed using Western blotting. The gene expression levels of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and Forkhead box O3a (FOXO3a) were assessed via qPCR. Our results revealed time- and concentration-dependent cytotoxic effects of empagliflozin and tamoxifen whether administered separately or in combination. While tamoxifen exhibits potency with an IC50 value of 17 μM, approximately ten times greater than that of empagliflozin (IC50 = 177 μM), synergistic effects are observed when the concentrations of the two agents approach their respective IC50 values. Additionally, empagliflozin significantly increases AMPKα activity while concurrently inhibiting Akt, p70S6K1, and p38 MAPKα, and these effects are significantly enhanced when empagliflozin is combined with tamoxifen. Moreover, empagliflozin modulates the gene expression, downregulating PGC-1α while upregulating FOXO3a. Empagliflozin exerts anti-proliferative and anti-survival effects by inhibiting mTOR, Akt, and PGC-1α, and it exhibits synergy with tamoxifen in MCF-7 breast cancer cells.
Graphical Abstract
Proposed anticancer mechanism of empagliflozin in MCF-7 breast cancer cells.