Reactive Oxygen Species

Publication Title: 
The Journal of Antimicrobial Chemotherapy

Plasmodium berghei ANKA infected C57B1/6 mice develop cerebral malaria at a parasitaemia of 15-25%. When parasitaemia reached 10%, P. berghei infected mice were treated with artemether, chloroquine or clindamycin in order to prevent the occurrence of cerebral malaria. Artemether and chloroquine were highly efficient. Functional tests revealed that zymosan stimulated spleen cells from untreated mice with cerebral malaria showed a slight decrease in their capacity to produce reactive oxygen intermediates (ROI) when compared with naive mice.

Prada, J.
Müller, S.
Bienzle, U.
Kremsner, P. G.
Publication Title: 
The Journal of Antimicrobial Chemotherapy

The effect of dihydroartemisinin, artemisinin and artesunate (0.1, 0.5, 5 and 50 mg/L) on phagocytic function and release of reactive oxygen products by neutrophils was studied by flow cytometry. Incubation with dihydroartemisinin, artemisinin and artemether resulted in a decreased capacity to phagocytose Escherichia coli (0.1-50 mg/L: 62-40%, 66-32% and 59-47% of the control values, respectively; P < 0.001 for all).

Wenisch, C.
Parschalk, B.
Zedwitz-Liebenstein, K.
Wernsdorfer, W.
Graninger, W.
Publication Title: 
Antimicrobial Agents and Chemotherapy

We recently described a screening system designed to detect neurotoxicity of artemisinin derivatives based on primary neuronal brain stem cell cultures (G. Schmuck and R. K. Haynes, Neurotoxicity Res. 2:37-49, 2000). Here, we probe possible mechanisms of this brain stem-specific neurodegeneration, in which artemisinin-sensitive neuronal brain stem cell cultures are compared with nonsensitive cultures (cortical neurons, astrocytes). Effects on the cytoskeleton of brain stem cell cultures, but not that of cortical cell cultures, were visible after 7 days.

Schmuck, Gabriele
Roehrdanz, Elke
Haynes, Richard K.
Kahl, Regine
Publication Title: 
In Vivo (Athens, Greece)

The anti-malarial artesunate (ART) also inhibits the growth of cancer cells. The active moiety is an endoperoxide bridge whose cleavage generates reactive oxygen species and free radicals. We analyzed whether glutathione-related enzymes contribute to tumor resistance to ART and to the low toxicity of ART towards normal organs.

Efferth, Thomas
Volm, Manfred
Publication Title: 
Cancer Research

Nearly all cervical cancers are etiologically attributable to human papillomavirus (HPV) infection and pharmaceutical treatments targeting HPV-infected cells would be of great medical benefit. Because many neoplastic cells (including cervical cancer cells) overexpress the transferrin receptor to increase their iron uptake, we hypothesized that iron-dependent, antimalarial drugs such as artemisinin might prove useful in treating HPV-infected or transformed cells.

Disbrow, Gary L.
Baege, Astrid C.
Kierpiec, Katie A.
Yuan, Hang
Centeno, Jose A.
Thibodeaux, Clare A.
Hartmann, Dan
Schlegel, Richard
Publication Title: 
Infection and Immunity

Sequestration of Plasmodium falciparum-infected erythrocytes (Pf-IRBC) in postcapillary brain endothelium is a hallmark of cerebral malaria (CM) pathogenesis. There is a correlation between adherent Pf-IRBC and increased expression of intercellular cell adhesion molecule 1 (ICAM-1), which is also a receptor for Pf-IRBC on human brain microvascular endothelial cells (HBMEC). The underlying mechanism for the increased ICAM-1 expression has not been clearly defined. Therefore, we investigated the mechanisms of ICAM-1 expression on isolated HBMEC after exposure to Pf-IRBC.

Tripathi, Abhai K.
Sullivan, David J.
Stins, Monique F.
Publication Title: 
PloS One

BACKGROUND: A major obstacle for successful cancer treatment often is the development of drug resistance in cancer cells during chemotherapy. Therefore, there is an urgent need for novel drugs with improved efficacy against tumor cells and with less toxicity on normal cells. Artesunate (ART), a powerful anti-malarial herbal compound, has been shown to inhibit growth of various tumor cell lines in vitro and of xenografted Kaposi's sarcoma in mice in vivo. However, the molecular mechanisms by which ART exerts its cytotoxicity have not been elucidated.

Efferth, Thomas
Giaisi, Marco
Merling, Annette
Krammer, Peter H.
Li-Weber, Min
Publication Title: 
International Journal of Cancer. Journal International Du Cancer

Analogs of the malaria therapeutic, artemisinin, possess in vitro and in vivo anticancer activity. In this study, two dimeric artemisinins (NSC724910 and 735847) were studied to determine their mechanism of action. Dimers were >1,000 fold more active than monomer and treatment was associated with increased reactive oxygen species (ROS) and apoptosis induction. Dimer activity was inhibited by the antioxidant L-NAC, the iron chelator desferroxamine and exogenous hemin.

Stockwin, Luke H.
Han, Bingnan
Yu, Sherry X.
Hollingshead, Melinda G.
Elsohly, Mahmoud A.
Gul, Waseem
Slade, Desmond
Galal, Ahmed M.
Newton, Dianne L.
Bumke, Maja A.
Publication Title: 
Cancer Chemotherapy and Pharmacology

Pancreatic cancer is highly resistant to the currently available chemotherapeutic agents. Less than 5% of patients diagnosed with this disease could survive beyond 5 years. Thus, there is an urgent need for the development of novel, efficacious drugs that can treat pancreatic cancer. Herein we report the identification of artesunate (ART), a derivative of artemisinin, as a potent and selective antitumor agent against human pancreatic cancer cells in vitro and in vivo.

Du, Ji-Hui
Zhang, Hou-De
Ma, Zhen-Jian
Ji, Kun-Mei
Publication Title: 
Plant Cell Reports

The antimalarial sesquiterpene, artemisinin, is in short supply; demand is not being met, and the role of artemisinin in the plant is not well established. Prior work showed that addition of dimethyl sulfoxide (DMSO) to seedlings increased artemisinin in their shoots and this study further investigated that serendipitous observation. When in vitro-cultured Artemisia annua rooted shoots were fed different amounts of DMSO (0-2.0% v/v), artemisinin levels doubled and showed biphasic optima at 0.25 and 2.0% DMSO.

Mannan, Abdul
Liu, Chunzhao
Arsenault, Patrick R.
Towler, Melissa J.
Vail, Dan R.
Lorence, Argelia
Weathers, Pamela J.


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