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International Journal of Molecular... May 2024Garlic is known to have diverse effects on mammalian cells, being cytotoxic, especially to cancer cells, but also protect against oxidative stress. Mammalian erythrocyte...
Garlic is known to have diverse effects on mammalian cells, being cytotoxic, especially to cancer cells, but also protect against oxidative stress. Mammalian erythrocyte is a simple cell devoid of intracellular organelles, protein synthesis ability, and most signaling pathways. Therefore, examination of the effects of garlic on erythrocytes allows for revealing primary events in the cellular action of garlic extract. In this study, human erythrocytes or erythrocyte membranes were exposed to garlic extract at various dilutions. Hemoglobin oxidation to methemoglobin, increased binding of hemoglobin to the membrane, and formation of Heinz bodies were observed. Garlic extract depleted acid-soluble thiols, especially glutathione, and induced a prooxidative shift in the cellular glutathione redox potential. The extract increased the osmotic fragility of erythrocytes, induced hemolysis, and inhibited hemolysis in isotonic ammonium chloride, indicative of decreased membrane permeability for Cl and increased the membrane fluidity. Fluorescent probes indicated an increased level of reactive oxygen species and induction of lipid peroxidation, but these results should be interpreted with care since the extract alone induced oxidation of the probes (dichlorodihydrofluorescein diacetate and BODIPY C11). These results demonstrate that garlic extract induces oxidative changes in the erythrocyte, first of all, thiol and hemoglobin oxidation.
Topics: Garlic; Humans; Plant Extracts; Erythrocytes; Hemolysis; Oxidation-Reduction; Lipid Peroxidation; Hemoglobins; Erythrocyte Membrane; Oxidative Stress; Reactive Oxygen Species; Glutathione; Osmotic Fragility
PubMed: 38791153
DOI: 10.3390/ijms25105115 -
Malaria Journal May 2024Primaquine (PQ) is the prototype 8-aminoquinoline drug, a class which targets gametocytes and hypnozoites. The World Health Organization (WHO) recommends adding a single... (Clinical Trial)
Clinical Trial
BACKGROUND
Primaquine (PQ) is the prototype 8-aminoquinoline drug, a class which targets gametocytes and hypnozoites. The World Health Organization (WHO) recommends adding a single low dose of primaquine to the standard artemisinin-based combination therapy (ACT) in order to block malaria transmission in regions with low malaria transmission. However, the haemolytic toxicity is a major adverse outcome of primaquine in glucose-6-phosphate dehydrogenase (G6PD)-deficient subjects. This study aimed to characterize the pharmacokinetic properties of primaquine and its major metabolites in G6PD-deficient subjects.
METHODS
A single low-dose of primaquine (0.4-0.5 mg/kg) was administered in twenty-eight African males. Venous and capillary plasma were sampled up to 24 h after the drug administration. Haemoglobin levels were observed up to 28 days after drug administration. Only PQ, carboxy-primaquine (CPQ), and primaquine carbamoyl-glucuronide (PQCG) were present in plasma samples and measured using liquid chromatography mass spectrometry. Drug and metabolites' pharmacokinetic properties were investigated using nonlinear mixed-effects modelling.
RESULTS
Population pharmacokinetic properties of PQ, CPQ, and PQCG can be described by one-compartment disposition kinetics with a transit-absorption model. Body weight was implemented as an allometric function on the clearance and volume parameters for all compounds. None of the covariates significantly affected the pharmacokinetic parameters. No significant correlations were detected between the exposures of the measured compounds and the change in haemoglobin or methaemoglobin levels. There was no significant haemoglobin drop in the G6PD-deficient patients after administration of a single low dose of PQ.
CONCLUSIONS
A single low-dose of PQ was haematologically safe in this population of G6PD-normal and G6PD-deficient African males without malaria. Trial registration NCT02535767.
Topics: Adolescent; Adult; Humans; Male; Middle Aged; Young Adult; Antimalarials; Glucosephosphate Dehydrogenase Deficiency; Primaquine
PubMed: 38773528
DOI: 10.1186/s12936-024-04979-y -
Biochemistry and Biophysics Reports Jul 2024hemoglobin is known to exhibit higher gamma radiation resistance compared to human hemoglobin. In the present study, we have introduced a sensitive method to analyze...
PURPOSE
hemoglobin is known to exhibit higher gamma radiation resistance compared to human hemoglobin. In the present study, we have introduced a sensitive method to analyze radiation-induced alterations in hemoglobin using Vibrational spectroscopy and further highlighting its potential for monitoring radiotoxicity in aquatic environments.
MATERIALS AND METHODS
Vibrational spectroscopic methods such as Raman and FT-IR spectroscopy were used to capture the distinctive chemical signature of hemoglobin (ChHb) under both and conditions. Any radiation dose-dependent shifts could be analyzed Human hemoglobin (HuHb) as standard reference.
RESULTS
Distinctive Raman peak detected at 930 cm-1 in (ChHb) was attributed to C-N stretching in the heterocyclic ring surrounding the iron atom, preventing heme degradation even after exposure to 2400 Gy dose. In contrast, for (HuHb), the transition from deoxy-hemoglobin to met-hemoglobin at 1210 cm-1 indicated a disruption in oxygen binding after exposure to 1200 Gy dose. Furthermore, while ChHb exhibited a consistent peak at 1652 cm-1 in FT-IR analysis, HuHb on the other hand, suffered damage after gamma irradiation.
CONCLUSION
The findings suggest that vibrational spectroscopic methods hold significant potential as a sensitive tool for detecting radiation-induced molecular alterations and damages. hemoglobin, with its robust interaction of the pyrrole ring with Fe, serves as a reliable bioindicator molecule to detect radiation damage using vibrational spectroscopic method.
PubMed: 38766383
DOI: 10.1016/j.bbrep.2024.101721 -
Toxicology May 2024The affinity of hemoglobin (Hb) to oxygen (O) influences processes of oxygen delivery and extraction at the tissue level. Despite cannabinoids being utilized or ingested...
The affinity of hemoglobin (Hb) to oxygen (O) influences processes of oxygen delivery and extraction at the tissue level. Despite cannabinoids being utilized or ingested in various ways, their possible impact on Hb-O affinity has barely been studied. This is an experimental ex-vivo trial. Venous blood samples were drawn from 5 male and 6 female healthy volunteers and subsequently exposed to different cannabinoid types: (delta-9-tetrahydrocannabinol [Δ9-THC], delta-8-tetrahydrocannabinol [Δ8-THC], cannabidiol [CBD]) at different concentrations. Oxygen dissociation curves (ODC) were measured and blood gas analyses were performed for methemoglobin (MetHb) determination. The results revealed no MetHb formation. Besides two statistically significant changes (+1.4mmHg and -0.9mmHg) in the female cohort, following Δ9-THC and Δ8-THC exposure, no further P changes could be observed. The study demonstrated an in-vitro effect of selected cannabinoids and dosages on P values in female participants, with variations not observed at other dosages, leaving the underlying mechanisms open for debate. MetHb formation, as potential mechanism, was not detected in this study. The precise reasons why changes only occurred at specific dosages remain unclear, indicating a need for further in-vivo research to understand the interaction between cannabinoids and Hb-O affinity completely.
PubMed: 38759720
DOI: 10.1016/j.tox.2024.153832 -
International Journal of Critical... 2024A 34-year-old Sri Lankan man presented with multiple episodes of vomiting following accidental ingestion of 100 ml of indoxacarb (Avaunt). He had a significant...
A 34-year-old Sri Lankan man presented with multiple episodes of vomiting following accidental ingestion of 100 ml of indoxacarb (Avaunt). He had a significant saturation gap (discrepancy between oxygen saturation [98%] in blood gas analysis and saturation on pulse oximetry [70%] in finger pulse oximetry), the color of the blood was muddy brown, and the methemoglobin level (60%) was high in the blood gas analysis. A diagnosis of methemoglobinemia secondary to indoxacarb poisoning was made, and he was treated with methylene blue with a favorable outcome. Methemoglobinemia secondary to indoxacarb poisoning is extremely rare, and clinicians should be aware of this important complication. Methemoglobinemia secondary to indoxacarb poisoning has a favorable outcome if recognized and treated promptly.
PubMed: 38715752
DOI: 10.4103/ijciis.ijciis_37_23 -
Practical Laboratory Medicine May 2024Acquired methemoglobinemia, predominantly due to oxidizing medications occurs when heme iron in hemoglobin is oxidized from ferrous to ferric ion and binds oxygen...
Acquired methemoglobinemia, predominantly due to oxidizing medications occurs when heme iron in hemoglobin is oxidized from ferrous to ferric ion and binds oxygen irreversibly leading to functional anemia, cyanosis, and tissue hypoxia. We report a case of a 60-year-old man with multiple comorbidities who was diagnosed with coronavirus disease 2019 (COVID-19) and developed methemoglobinemia after consumption of prescribed supplements. He presented with dyspnea and cyanosis. An oxygen saturation gap with characteristic chocolate-brown arterial blood indicated methemoglobinemia. Outsourced methemoglobin (MetHb) was increased at 9.0%. Despite aggressive intervention, he succumbed to his illness. In this case, we discuss the pathophysiology of why some individuals, especially the elderly with COVID-19 are more susceptible to develop methemoglobinemia after possibly being exposed to oxidizing agents. Laboratory methods for assessing oxygen saturation, including pulse oximetry, arterial blood gas and co-oximetry are examined in relation to this case. The importance of considering a diagnosis of methemoglobinemia based on clinical and biochemical findings although MetHb assay or co-oximetry are not readily available is also emphasized.
PubMed: 38707259
DOI: 10.1016/j.plabm.2024.e00395 -
Clinical Case Reports Apr 2024Treatment of congenital chyloperitoneum is a challenge. Conservative methods may be ineffective. Preoperative visualization of the site of lymphatic leakage is crucial,...
Treatment of congenital chyloperitoneum is a challenge. Conservative methods may be ineffective. Preoperative visualization of the site of lymphatic leakage is crucial, but radiological imaging is technically complicated and may not provide sufficient information, especially in small patients. To ease the detection of lymphatic leakage during surgery, preoperative feeding with fat-rich formula with Sudan Black has been recommended. However, administration of Sudan Black may result in life-threatening methemoglobinemia and liver damage without any advantage of revealing leakage during surgery. We recommend preoperative feeding with pure fat-rich formula.
PubMed: 38585587
DOI: 10.1002/ccr3.8676 -
Dermatology and Therapy Apr 2024Systemic toxicity of eutectic mixture of local anesthetics (EMLA) cream is rare and is most commonly observed in children, for example, upon extensive application, and...
INTRODUCTION
Systemic toxicity of eutectic mixture of local anesthetics (EMLA) cream is rare and is most commonly observed in children, for example, upon extensive application, and rarely occurs in adults with certain dispositions.
CASE REPORT
We report the case of a 71-year-old man who developed methemoglobinemia and systemic intoxication upon topical application of EMLA cream for leg ulcer and stasis dermatitis prior to surgical debridement. Approximately 45 min after application, the patient was found to be in a somnolent state, was unable to articulate, and showed peripheral cyanosis. The blood concentration of methemoglobin (MetHb) was 15.1%, and therefore, a diagnosis of systemic toxicity of EMLA due to methemoglobinemia was established. After removal of the cream, oxygen was applied, and further observation revealed that the patient's condition rapidly improved without any residue. In the following, we also discuss literature related to systemic EMLA intoxication.
CONCLUSION
EMLA cream may cause severe systemic toxicity even in adults under certain conditions, for example, when applied on damaged skin or in extensive amounts.
PubMed: 38568445
DOI: 10.1007/s13555-024-01139-7 -
Toxicology Reports Jun 2024Methemoglobinemia is a potentially life-threatening condition caused by the formation of methemoglobin, a form of hemoglobin that cannot bind oxygen. While there are...
Methemoglobinemia is a potentially life-threatening condition caused by the formation of methemoglobin, a form of hemoglobin that cannot bind oxygen. While there are some rare congenital causes of methemoglobinemia, most cases are acquired from the effects of specific drugs or environmental exposures. In this retrospective study, we analyzed a large data set of whole blood samples analyzed for methemoglobin at an academic medical center in Midwestern United States that provides both pediatric and adult services. For a 14 year timeframe (May 2009- June 2023), we performed detailed chart analysis of all patients with a methemoglobin concentration of 3.1 % or higher. For an earlier 13 year timeframe (January 1996-April 2009), we performed chart review for all patients with a methemoglobin concentration of 10.0 % or higher. For the 2009-2023 data, dapsone was the most frequent cause of methemoglobinemia (methemoglobin 3.1 % or higher) in both pediatric (73.3 %, 115 clinical encounters, 105 unique patients) and adult (65.3 %, 195 clinical encounters, 190 unique patients) populations. Inhaled nitric oxide as medical therapy was the next most frequent cause in both pediatric (18.1 %) and adult (13.2 %) populations. Causes associated with two or more unique episodes with methemoglobin concentrations of 10.0 % and higher included the following: dapsone (n = 40 episodes), benzocaine (n = 10), recreational use of amyl or isobutyl nitrite (n = 3), suicide attempt with sodium nitrite (n = 3 with 1 fatality; all 3 cases within last 3 years), food contaminated with nitrates (n = 2), and sepsis (n = 2). A total of 18 patients received treatment with methylene blue including 5 cases associated with benzocaine and all of the cases associated with amyl nitrite, isobutyl nitrite, sodium nitrite, and contaminated food. Only 3 patients with dapsone-associated methemoglobinemia received methylene blue, reflecting primary management by dose reduction or discontinuation of drug. Overall, our data reinforce previous studies showing dapsone, inhaled nitric oxide, and nitrites as common agents causing methemoglobinemia in a patient population seen at a medical center. Our data also are consistent with recent epidemiology trends showing increase in suicide attempts using sodium nitrite.
PubMed: 38544956
DOI: 10.1016/j.toxrep.2024.03.004