Realgar (90% of AS4S4) and cinnabar (96% of HgS) have been used in traditional Chinese medicines for thousands of years. Both arsenic and mercury are well-known for toxic effects and the safety of realgar-and cinnabar-containing traditional Chinese medicines is of concern. It is considered that any intentional use of known toxic metals in medicine is an unacceptable risk, while an opposing opinion presumes that realgar and cinnabar have clear pharmacological action with tolerable side effects. This review summarized the progress of toxicological study on realgar-and cinnbar-containing traditional Chinese medicines.
Arsenicals ; adverse effects ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Medicine, Chinese Traditional ; adverse effects ; Mercury Compounds ; adverse effects ; Sulfides ; adverse effects

Adult ; Air Pollutants, Occupational ; adverse effects ; analysis ; Arsenicals ; adverse effects ; analysis ; Female ; Humans ; Male ; Metallurgy ; Middle Aged ; Occupational Exposure ; adverse effects ; Young Adult

Qinghuang Powder (QHP), an oral arsenic, has become an effective drug in the treatment of myelodysplastic syndromes (MDS) in Xiyuan Hospital, China Academy of Chinese Medical Sciences for many years, and the action mechanism of the compound or active ingredient As₂S₂ of QHP has been elucidated. Considering the relatively safety, chemotherapy-free and convenient oral profile, QHP is widely used in the clinical treatment for MDS patients, especially for elderly patients. In this review, the authors document the efficacy and safety of oral arsenic-containing compound QHP in the treatment of MDS, with a special focus on the association of efficacy of QHP with the cytogenetics, prognostic risk, DNA methylation, gene mutation, blood arsenic concentration, mechanism of action of As₂S₂ and the countermeasures against adverse reactions of gastrointestinal tract.
Aged ; Arsenic/therapeutic use* ; Arsenicals/adverse effects* ; Drugs, Chinese Herbal ; Humans ; Myelodysplastic Syndromes/genetics* ; Powders/therapeutic use*

OBJECTIVETo investigate cardiac effects of arsenic trioxide (As(2)O(3)) at conventional dosage in acute promyelocytic leukemia (APL) patients.

METHODSThe basical heart rate, electrocardiograph, plasma As(2)O(3) concentration of APL patients were dynamically monitored. The action potential duration and current of I(Ca-L) in guinea pig cardiac ventricular myocytes were assayed by patch clamp technique, and the elevated cytosolic [Ca(2+)]i of guinea pig ventricular myocytes induced by As(2)O(3) by laser confocal microscopy.

RESULTSApproximately 52.5% - 35% of 40 APL patients manifested poor cardiac effects of different degree when As(2)O(3) intravenous infused at conventional doses in the initial 1 or 2 weeks with fast heart rate or prolonged QT interval. As(2)O(3) at concentration of 1, 2, 5 micro mol/L prolonged action potential duration from (563.0 +/- 55.8) ms to (737.7 +/- 131.7), (842.4 +/- 115.6) and (1103.2 +/- 96.3) ms respectively (P < 0.05, P < 0.01, P < 0.01), and increased I(Ca-L) of guinea pig cardiac ventricular myocytes as well as the respectively cytosolic [Ca(2+)]i. Calcium channel blocking agent can cut-out the effect.

CONCLUSIONAs(2)O(3) intravenous infusion at conventional doses can cause tachycardia and prolong QT interval. The probable mechanism might be that As(2)O(3) affects the ion channels and cytosolic calcium.

Adult ; Animals ; Antineoplastic Agents ; adverse effects ; Arsenicals ; adverse effects ; blood ; Calcium ; metabolism ; Calcium Channels, L-Type ; drug effects ; Cricetinae ; Electrocardiography ; drug effects ; Female ; Heart ; drug effects ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; Male ; Oxides ; adverse effects ; blood

OBJECTIVETo explore arsenic accumulation and toxicity mechanism following long-term use of realgar and provide scientific basis for safety use of realgar in clinic.

METHODThe realgar which was used in the study contains 90% insoluble asenic sulfide (As2S2) and 1.696 mg x kg(-1) soluble arsenic. Two separate experiments were performed: 1) Twenty-eight fasting SD rats were orally given a single dose of realgar at the dose of 0.8 g x kg(-1) and the other four rats were given ultra-filtrated water served as control group. Blood, hearts, livers, kidneys, lungs and brains of four rats were taken out at 0.5, 1, 2, 4, 8, 16, 36 h respectively after treatment. Asenic quantity of each organ or blood sample was measured. 2) Forty SD rats were randomly divided into four groups: control group and realgar 0.02, 0.08, 0.16 g x kg(-1) groups, each group containing 5 females and 5 males. The rats were intra-gastrically treated with realgar once a day for successively 90 days, while the control group was given ultra-filtrated water. Asenic amount in blood, liver, kidney and brain of each rat was measured in fasting rats at 16 h after last dosing.

RESULTAsenic amount of blood, liver, kidney, heart, lung and brain increased after single dosing of realgar at dose of 0.16 g x kg(-1), with the order from high to low blood > kidney > lung > liver > heart > brain. Asenic amount was much higher in blood than that in other organs. The feature of asenic distribution in blood following realgar administration may be the basis for its use for leukemia Ninety-day oral treatment of realgar led to significant accumulation of asenic in blood, kidney, liver and brain. The highest asenic accumulation times was found in kidney followed by liver, which was assumed to be associated with nephrotoxicity and hepatotoxicity of realgar. The highest amount of asenic was observed in blood after 90 day's administration of realgar, and the amount of asenic in organs was in the order of blood > kidney > liver > brain.

CONCLUSIONAsenic can be absorbed and extensively distributed in various organs or tissesses after realgar administration in rats. Long-term use of realgar caused high asenic accumulation in various tissueses, including blood, kidney, liver, and brain. The nephrotoxicity and hepatotoxicity of realgar could be associated with the asenic accumulation in relative organs. Blood is the target of the most highest distribution and accamulation of asenic after realgar treatment, that could be associated with the efficacy of realgar on the treatment of leakemia.

Animals ; Arsenic ; analysis ; chemistry ; pharmacokinetics ; toxicity ; Arsenicals ; administration & dosage ; adverse effects ; chemistry ; Female ; Male ; Rats ; Rats, Sprague-Dawley ; Solubility ; Sulfides ; administration & dosage ; adverse effects ; chemistry ; Time Factors

Antineoplastic Agents ; therapeutic use ; Arsenicals ; adverse effects ; therapeutic use ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; Leukocytosis ; chemically induced ; Oxides ; adverse effects ; therapeutic use

Realgar-containing Niuhuang Jiedu tablet (NHJD) has been applied in clinic for more than 800 years. However, because realgar contains arsenic (As), it has aroused wide concerns and controversies both at home and abroad. Currently, there are two misunderstandings about realgar-containing Chinese patent medicines. First, some people exaggerated realgar's toxicity as that of arsenic. Second, they recommended to remove realgar from traditional Chinese medicine compounds. In this paper, the authors summarized the advance in studies on NHJD, and proposed different opinions: (1) It is inappropriate to take total As as the index in safety evaluation of NHJD. (2) The toxicity of NHJD is dependent on the dose and duration of administration. (3) Realgar is an active ingredient of NHJD, and shall be deeply studied. Classic realgar-containing traditional Chinese medicine prescriptions, such as Niuhuang Jiedu tablet, shall be evaluated with rigorous modern scientific basis, with the aim to guide rational and safe application.
Animals ; Arsenicals ; adverse effects ; chemistry ; therapeutic use ; Chemistry, Pharmaceutical ; methods ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; adverse effects ; chemistry ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; adverse effects ; methods ; Sulfides ; adverse effects ; chemistry ; therapeutic use ; Tablets ; Time Factors ; Treatment Outcome

Adult ; Aged ; Antineoplastic Agents ; adverse effects ; therapeutic use ; Arsenicals ; adverse effects ; therapeutic use ; Chemical and Drug Induced Liver Injury ; Female ; Humans ; Liver Neoplasms ; drug therapy ; Male ; Middle Aged ; Oxides ; adverse effects ; therapeutic use ; Remission Induction ; Treatment Outcome ; Vomiting ; chemically induced

OBJECTIVETo compare the efficacy and adverse effects between arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) in patients with acute promyelocytic leukemia (APL).

METHODSThe clinical data of 71 patients with newly diagnosed APL were retrospectively analyzed. Two groups were classified according to the induction regimens, namely ATO group (n = 41) and ATRA group (n = 30). The complete remission (CR) rate and the time to CR were compared between these two groups.

RESULTSThe CR rate was 97.5% in ATO group and 93.3% in ATRA group (P > 0.05). The median time to CR was 29 days (21-45 days) in ATO group, which was significantly shorter than 38.5 days (24-63 days) in ATRA group (P < 0.001). Retinoic acid syndrome occurred in 52.9% of patients treated with ATRA, which affected the further use of ATRA.

CONCLUSIONSBoth ATO and ATRA have high response rates for newly diagnosed patients with APL. Compared with ATRA, ATO induction therapy has shorter time to achieve CR and less adverse effects, and therefore may be the first-line therapy for APL.

Adolescent ; Adult ; Aged ; Arsenicals ; adverse effects ; therapeutic use ; Female ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; Male ; Middle Aged ; Oxides ; adverse effects ; therapeutic use ; Remission Induction ; Retrospective Studies ; Treatment Outcome ; Tretinoin ; adverse effects ; therapeutic use ; Young Adult

Antineoplastic Agents ; administration & dosage ; adverse effects ; Arsenicals ; administration & dosage ; adverse effects ; Cerebral Hemorrhage ; chemically induced ; Humans ; Infusions, Intravenous ; Leukemia, Promyelocytic, Acute ; drug therapy ; Leukocytosis ; chemically induced ; Oxides ; administration & dosage ; adverse effects