The Herbal Constituents in An-Gong-Niu-Huang Wan (AGNH) Protect against Cinnabar- and Realgar-Induced Hepatorenal Toxicity and Accumulations of Mercury and Arsenic in Mice

An-Gong-Niu-Huang Wan (AGNH) has been a well-known cinnabar- and realgar-containing compound recipe for cerebral diseases. Unfortunately, its clinical practice is often restrained by the specific hepatorenal toxicity of cinnabar and realgar (C + R). In previous research studies, we have found that the antioxidative and anti-inflammatory effects of its herbal constituents could mitigate the risks from the toxicity. The underlying detoxification mechanisms are still unsolved. The present study investigated the protective effects of AGNH’s herbal constituents on hepatorenal injury induced by C + R. For the mice treated with C + R, the increased expression levels of sensitive biomarkers of metal exposure and hepatorenal toxicity, including metallothionein (MT) in both hepatorenal tissues and kidney induced molecule-1 (KIM-1) in the kidney, were simultaneously reduced when C + R coadministered with other herbal medicines. In addition, the contents of trivalent As (AsIII), pentavalent As (Asv), and mercury (Hg) in hepatorenal tissues of mice were also significantly reduced benefiting from the herbal constituents in AGNH. Further mechanism studies showed that the herbal constituents in AGNH could downregulate the expressions of uptake transporters (AQP9 and OAT1) and upregulate the expressions of efflux transporters (P-gp, MRP2, and MRP4) in mice intoxicated by C + R. Our results suggested that AGNH’s herbal constituents protect the body against C + R-induced hepatorenal toxicity and accumulations of Hg and As, which could be associated with the reestablishment of heavy metal homeostasis and the detoxification system.

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Ultrastructural, Confocal and Viscoelastic Characteristics of Whole Blood and Plasma After Exposure to Cadmium and Chromium Alone and in Combination: An Ex Vivo Study

Cellular Physiology and Biochemistry ◽

10.1159/000481841 ◽

2017 ◽

Vol 43 (3) ◽

pp. 1288-1300 ◽

Cited By ~ 5

Author(s):

Chantelle Venter ◽

Hester Magdalena Oberholzer ◽

Janette Bester ◽

Mia-Jeanne van Rooy ◽

Megan Jean Bester

Keyword(s):

Heavy Metals ◽

Heavy Metal ◽

Blood Coagulation ◽

Ex Vivo ◽

The Body ◽

Laser Scanning Microscopy ◽

Ultrastructural Changes ◽

Target System ◽

Metal Exposure ◽

Confocal Laser

Background/Aims: Heavy metal pollution is increasing in the environment, contaminating water, food and air supplies. This can be linked to many anthropogenic activities. Heavy metals are absorbed through the skin, inhalation and/or orally. Irrespective of the manner of heavy metal entry in the body, the blood circulatory system is potentially the first to be affected following exposure and adverse effects on blood coagulation can lead to associated thrombotic disease. Although the plasma levels and the effects of cadmium (Cd) and chromium (Cr) on erythrocytes and lymphocytes have been described, the environmental exposure to heavy metals are not limited to a single metal and often involves metal mixtures, with each metal having different rates of absorption, different cellular, tissue, and organ targets. Therefore the aim of this study is to investigate the effects of the heavy metals Cd and Cr alone and whether Cr synergistically increases the effect of Cd on physiological important processes such as blood coagulation. Methods: Human blood was exposed to the heavy metals ex vivo, and thereafter morphological analysis was performed with scanning electron- and confocal laser scanning microscopy (CLSM) in conjunction with thromboelastography®. Results: The erythrocytes, platelets and fibrin networks presented with ultrastructural changes, including varied erythrocytes morphologies, activated platelets and significantly thicker fibrin fibres in the metal-exposed groups. CLSM analysis revealed the presence of phosphatidylserine on the outer surface of the membranes of the spherocytic erythrocytes exposed to Cd and Cr alone and in combination. The viscoelastic analysis revealed only a trend that indicates that clots that will form after heavy metal exposure, will likely be fragile and unstable especially for Cd and Cr in combination. Conclusion: This study identified the blood as an important target system of Cd and Cr toxicity.

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The Role of Uptake and Efflux Transporters in the Disposition of Glucuronide and Sulfate Conjugates

Frontiers in Pharmacology ◽

10.3389/fphar.2021.802539 ◽

2022 ◽

Vol 12 ◽

Author(s):

Erkka Järvinen ◽

Feng Deng ◽

Wilma Kiander ◽

Alli Sinokki ◽

Heidi Kidron ◽

...

Keyword(s):

Phase Ii ◽

Organic Anion ◽

The Body ◽

Cell Membrane Permeability ◽

Intestinal Lumen ◽

Efflux Transporters ◽

Cancer Resistance ◽

Multidrug Resistance Proteins ◽

Uptake Transporters

Glucuronidation and sulfation are the most typical phase II metabolic reactions of drugs. The resulting glucuronide and sulfate conjugates are generally considered inactive and safe. They may, however, be the most prominent drug-related material in the circulation and excreta of humans. The glucuronide and sulfate metabolites of drugs typically have limited cell membrane permeability and subsequently, their distribution and excretion from the human body requires transport proteins. Uptake transporters, such as organic anion transporters (OATs and OATPs), mediate the uptake of conjugates into the liver and kidney, while efflux transporters, such as multidrug resistance proteins (MRPs) and breast cancer resistance protein (BCRP), mediate expulsion of conjugates into bile, urine and the intestinal lumen. Understanding the active transport of conjugated drug metabolites is important for predicting the fate of a drug in the body and its safety and efficacy. The aim of this review is to compile the understanding of transporter-mediated disposition of phase II conjugates. We review the literature on hepatic, intestinal and renal uptake transporters participating in the transport of glucuronide and sulfate metabolites of drugs, other xenobiotics and endobiotics. In addition, we provide an update on the involvement of efflux transporters in the disposition of glucuronide and sulfate metabolites. Finally, we discuss the interplay between uptake and efflux transport in the intestine, liver and kidneys as well as the role of transporters in glucuronide and sulfate conjugate toxicity, drug interactions, pharmacogenetics and species differences.

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Analysis of Lead Heavy Metal (Pb) Contamination on Matte Lipstick Preparations for Sale in Banda Aceh City Aceh Market

Serambi Journal of Agricultural Technology ◽

10.32672/sjat.v2i1.2053 ◽

2020 ◽

Vol 2 (1) ◽

Author(s):

Rizki Andalia ◽

Mulia Aria Suzanni ◽

Rini Rini

Keyword(s):

Heavy Metal ◽

Atomic Absorption ◽

Atomic Absorption Spectrophotometry ◽

The Body ◽

Permissible Limit ◽

The Sun ◽

Absorption Spectrophotometry ◽

Pb Contamination ◽

Body Organ ◽

Banda Aceh

Lipstick or lip dye is a cosmetic dose that serves to coloring, decorative the lips, as a moisturizing material and protect the lips from exposure the sun to provide optimum results. Lipstick should not contain chemicals such as lead (Pb) because the Pb is a heavy metal that is very dangerous when continuously used on the skin, because it will be absorbed into the blood and attack the body organ causing the onset of disease. According to BPOM that the lead rate on the lipstick does not exceed the permissible limit of 20 mg/kg or 20 ppm.This research aims to know the levels contained in the samples are 4 brands of matte lipstick that are sold in the Aceh market in Banda Aceh City with the method of atomic absorption spectrophotometry (AAS). The results showed that on the 4 brands of lipstick matte contain heavy metal lead (Pb) with a rate still qualified allowed by BPOM is samples A, B, C, and D, respectively at 0.24 ppm; 0.10 ppm; 2.87 ppm and 1.32 ppm, so that the 4 brands of lipstick matte are still used.

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The antitoxic and protective effects of Curcuma longa and it`s active agent, Curcumin: оverview

Terapevt (General Physician) ◽

10.33920/med-12-2006-09 ◽

2020 ◽

pp. 66-72

Author(s):

A. Khisamova ◽

O. Gizinger

Keyword(s):

Curcuma Longa ◽

Physiological Activity ◽

Active Agent ◽

Modern Science ◽

Physical Exertion ◽

The Body ◽

Modern World ◽

Protective Effects ◽

Daily Stress ◽

Anti Cancer

In the modern world, where a person is exposed to daily stress, increased physical exertion, the toxic effect of various substances, including drugs. The task of modern science is to find antioxidants for the body. These can be additives obtained both synthetically and the active substances that we get daily from food. Such a striking example is turmeric, obtained from the plant Curcuma longa. Recently, it has been known that curcumin has an antioxidant, anti-inflammatory, anti-cancer effect and, thanks to these effects, plays an important role in the prevention and treatment of various diseases, in particular, from cancer to autoimmune, neurological, cardiovascular and diabetic diseases. In addition, much attention is paid to increasing the biological activity and physiological effects of curcumin on the body through the synthesis of curcumin analogues. This review discusses the chemical and physical characteristics, analogues, metabolites, the mechanisms of its physiological activity and the effect of curcumin on the body.

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Current Advances in the Biological Activity of Polysaccharides in Dendrobium with Intriguing Therapeutic Potential

Current Medicinal Chemistry ◽

10.2174/0929867324666170227114648 ◽

2018 ◽

Vol 25 (14) ◽

pp. 1663-1681 ◽

Cited By ~ 9

Author(s):

Chun-Ting Lee ◽

Heng-Chun Kuo ◽

Yung-Hsiang Chen ◽

Ming-Yen Tsai

Keyword(s):

Biological Activity ◽

Therapeutic Potential ◽

Biological Activities ◽

Biological Effects ◽

Herbal Medicines ◽

Research Field ◽

Protective Effects ◽

Pharmacological Effects ◽

The Family ◽

Anti Tumor Activity

The polysaccharides in many plants are attracting worldwide attention because of their biological activities and medical properties, such as anti-viral, anti-oxidative, antichronic inflammation, anti-hypertensive, immunomodulation, and neuron-protective effects, as well as anti-tumor activity. Denodrobium species, a genus of the family orchidaceae, have been used as herbal medicines for hundreds of years in China due to their pharmacological effects. These effects include nourishing the Yin, supplementing the stomach, increasing body fluids, and clearing heat. Recently, numerous researchers have investigated possible active compounds in Denodrobium species, such as lectins, phenanthrenes, alkaloids, trigonopol A, and polysaccharides. Unlike those of other plants, the biological effects of polysaccharides in Dendrobium are a novel research field. In this review, we focus on these novel findings to give readers an overall picture of the intriguing therapeutic potential of polysaccharides in Dendrobium, especially those of the four commonly-used Denodrobium species: D. huoshanense, D. offininale, D. nobile, and D. chrysotoxum.

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Heavy metal detoxification mechanisms by microalgae: Insights from transcriptomics analysis

Environmental Pollution ◽

10.1016/j.envpol.2021.117443 ◽

2021 ◽

pp. 117443

Author(s):

Shweta Tripathi ◽

Krishna Mohan Poluri

Keyword(s):

Heavy Metal ◽

Metal Detoxification ◽

Heavy Metal Detoxification ◽

Detoxification Mechanisms

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Bioaccessibility-corrected health risk of heavy metal exposure via shellfish consumption in coastal region of China

Environmental Pollution ◽

10.1016/j.envpol.2021.116529 ◽

2021 ◽

Vol 273 ◽

pp. 116529

Author(s):

Minwei Chai ◽

Ruili Li ◽

Yuan Gong ◽

Xiaoxue Shen ◽

Lingyun Yu

Keyword(s):

Heavy Metal ◽

Health Risk ◽

Coastal Region ◽

Metal Exposure ◽

Heavy Metal Exposure

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Relationship between heavy metal exposure and type 2 diabetes: a large-scale retrospective cohort study using occupational health examinations

BMJ Open ◽

10.1136/bmjopen-2020-039541 ◽

2021 ◽

Vol 11 (3) ◽

pp. e039541

Author(s):

Jun Ho Ji ◽

Mi Hyeon Jin ◽

Jung-Hun Kang ◽

Soon Il Lee ◽

Suee Lee ◽

...

Keyword(s):

Heavy Metals ◽

Type 2 Diabetes ◽

Heavy Metal ◽

Cohort Study ◽

Retrospective Cohort ◽

Metal Exposure ◽

Heavy Metal Exposure ◽

Lead And Cadmium

ObjectivesTo investigate the associations between heavy metal exposure and serum ferritin levels, physical measurements and type 2 diabetes mellitus (DM).DesignA retrospective cohort study.SettingChangwon, the location of this study, is a Korean representative industrial city. Data were obtained from medical check-ups between 2002 and 2018.ParticipantsA total of 34 814 male subjects were included. Of them, 1035 subjects with lead exposure, 200 subjects with cadmium exposure and the 33 579 remaining were assigned to cohort A, cohort B and the control cohort, respectively. Data including personal history of alcohol and smoking, age, height, weight, the follow-up duration, haemoglobin A1c (HbA1c), fasting blood sugar (FBS), ferritin levels, and lead and cadmium levels within 1 year after exposure were collected.Primary outcome measureIn subjects without diabetes, changes in FBS and HbA1c were analysed through repeated tests at intervals of 1 year or longer after the occupational exposure to heavy metals.ResultsIn Cohort A, DM was diagnosed in 33 subjects. There was a significant difference in lead concentrations between the subjects diagnosed with DM and those without DM during the follow-up period (3.94±2.92 mg/dL vs 2.81±2.03 mg/dL, p=0.002). Simple exposure to heavy metals (lead and cadmium) was not associated with DM in Cox regression models (lead exposure (HR) 1.01, 95% CI: 0.58 to 1.77, p 0.971; cadmium exposure HR 1.48, 95% CI: 0.61 to 3.55, p=0.385). Annual changes in FBS according to lead concentration at the beginning of exposure showed a positive correlation (r=0.072, p=0.032).ConclusionOur findings demonstrated that simple occupational exposure to heavy metals lead and cadmium was not associated with the incidence of DM. However, lead concentrations at the beginning of the exposure might be an indicator of DM and glucose elevations.

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Expression and Function of Organic Anion Transporting Polypeptides in the Human Brain: Physiological and Pharmacological Implications

Pharmaceutics ◽

10.3390/pharmaceutics13060834 ◽

2021 ◽

Vol 13 (6) ◽

pp. 834

Author(s):

Anima M. Schäfer ◽

Henriette E. Meyer zu Schwabedissen ◽

Markus Grube

Keyword(s):

Organic Anion ◽

Physiological Role ◽

Point Of View ◽

Efflux Transporters ◽

Organic Anion Transporting Polypeptides ◽

Current State ◽

P Glycoprotein ◽

The Central Nervous System ◽

And Function ◽

Uptake Transporters

The central nervous system (CNS) is an important pharmacological target, but it is very effectively protected by the blood–brain barrier (BBB), thereby impairing the efficacy of many potential active compounds as they are unable to cross this barrier. Among others, membranous efflux transporters like P-Glycoprotein are involved in the integrity of this barrier. In addition to these, however, uptake transporters have also been found to selectively uptake certain compounds into the CNS. These transporters are localized in the BBB as well as in neurons or in the choroid plexus. Among them, from a pharmacological point of view, representatives of the organic anion transporting polypeptides (OATPs) are of particular interest, as they mediate the cellular entry of a variety of different pharmaceutical compounds. Thus, OATPs in the BBB potentially offer the possibility of CNS targeting approaches. For these purposes, a profound understanding of the expression and localization of these transporters is crucial. This review therefore summarizes the current state of knowledge of the expression and localization of OATPs in the CNS, gives an overview of their possible physiological role, and outlines their possible pharmacological relevance using selected examples.

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