Answer to the comment of Hai Lu et al. regarding “Hepatotoxicity by combination treatment of temozolomide, artesunate and Chinese herbs in a glioblastoma multiforme patient: case report and review of the literature. Arch Toxicol (2016)”

Efferth, Thomas; Schöttler, Ursula; Krishna, Sanjeev; Schmiedek, Peter; Wenz, Frederik; Giordano, Frank A.

doi:10.1007/s00204-017-1958-1

Cited by 2 publications

(1 citation statement)

References 4 publications

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“…Treatment with artesunate has been reported to lead to occasional and transient side effects, including hematological toxicity, gastrointestinal toxicity, asthenia and thrombosis, in colon, cervix and breast carcinoma (42-44). Rare cases of hepatotoxicity have been reported with artesunate (93,94). Whether phytotherapeutic approaches with A. annua are safer than treatment with artesunate requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

Retrospective study of small pet tumors treated with Artemisia annua and iron

Saeed

Breuer²,

Hegazy

2019

Int J Oncol

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Artemisinin from Artemisia annua L. and its derivatives are well-known antimalarial drugs. In addition, in vitro studies, in vivo studies and clinical trials have demonstrated that these drugs exhibit anticancer activity in human patients with cancer. Therefore, the aim of the present study was to investigate whether a phytotherapeutic A. annua preparation exerts anticancer activity in veterinary tumors of small pets. Dogs and cats with spontaneous cancer (n=20) were treated with standard therapy plus a commercial A. annua preparation (Luparte®) and compared with a control group treated with standard therapy alone (n=11). Immunohistochemical analyses were performed with formalin-fixed paraffin-embedded tumor biopsies to analyze the expression of transferrin receptor (TfR) and the proliferation marker Ki-67 as possible biomarkers to assess treatment response of tumors to A. annua. Finally, the expression levels of TfR and Ki-67 were compared with the IC50 values towards artemisinin in two dog tumor cells lines (DH82 and DGBM) and a panel of 54 human tumor cell lines. Retrospectively, the present study assessed the survival times of small animals treated by standard therapy with or without A. annua. A. annua treatment was associated with a significantly higher number of animals surviving >18 months compared with animals without A. annua treatment (P=0.0331). Using a second set of small pet tumors, a significant correlation was identified between TfR and Ki-67 expression by immunohistochemistry (P=0.025). To further assess the association of transferrin and Ki-67 expression with cellular response to artemisinin, the present study compared the expression of these two biomarkers and the IC50 values for artemisinin in National Cancer Institute tumor cell lines in vitro. Both markers were inversely associated with artemisinin response (P<0.05), and the expression levels of TfR and Ki-67 were significantly correlated (P=0.008). In conclusion, the promising results of the present retrospective study warrant further confirmation by prospective studies in the future.

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Section: Discussionmentioning

confidence: 99%

Retrospective study of small pet tumors treated with Artemisia annua and iron

Saeed

Breuer²,

Hegazy

2019

Int J Oncol

Self Cite

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Immune-mediated herb-induced liver injury: a potential association with herbal artemisinin use as supported by the updated RUCAM

Mathavan

Krekora

et al. 2023

BMJ Case Rep

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Immune-mediated herb-induced liver injury (HILI) is an acute or chronic inflammatory liver disease precipitated by a hepatotoxic agent with a presentation similar to acute autoimmune hepatitis. It is distinguished in clinical course from true autoimmune hepatitis by remission on drug discontinuation and immunosuppressive treatment. We report a potential case of immune-mediated HILI associated with artemisinin use, an herb underlying first-line malarial treatments, in a woman undergoing radiotherapy for right-sided pelvic sarcoma. A probable association in this case is supported by causality assessment using the updated Roussel Uclaf Causality Assessment Method (score of 6). She achieved clinical improvement with a course of oral corticosteroids and remained stable without relapse following discontinuation. Increased awareness of this complication is imperative, as literature to date only documents direct hepatocellular and cholestatic liver injury from artemisinin use, and should augment clinician counsel regarding complementary medicine administration, especially in high-risk individuals like those with cancer.

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Answer to the comment of Hai Lu et al. regarding “Hepatotoxicity by combination treatment of temozolomide, artesunate and Chinese herbs in a glioblastoma multiforme patient: case report and review of the literature. Arch Toxicol (2016)”

Cited by 2 publications

References 4 publications

Retrospective study of small pet tumors treated with Artemisia annua and iron

Retrospective study of small pet tumors treated with Artemisia annua and iron

Immune-mediated herb-induced liver injury: a potential association with herbal artemisinin use as supported by the updated RUCAM

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