Acute Liver Failure Secondary to Albendazole: Defining Albendazoleʼs Role in the Management of Echinococcal Infection

Aasen, Tyler; Nasrollah, Laya; Seetharam, Anil

doi:10.14309/00000434-201510001-00722

Cited by 2 publications

(2 citation statements)

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“…If lesions cannot be completely removed by surgery, a lifelong medication is required, usually using benzimidazoles, which can cause adverse side effects. For example, several cases with hepatotoxic effects due to treatment with the benzimidazole albendazole (ABZ) were reported with various outcomes [14][15][16][17]. An inadequate adherence to chemotherapy, due to adverse side effects, and development of resistance can explain the relapsing spread of AE and a worsening general condition of patients with severe E. multilocularis infiltrations [11,18,19].…”

Section: Introductionmentioning

confidence: 99%

Albendazole reduces hepatic inflammation and endoplasmic reticulum-stress in a mouse model of chronic Echinococcus multilocularis infection

et al. 2022

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Background Echinococcus multilocularis causes alveolar echinococcosis (AE), a rising zoonotic disease in the northern hemisphere. Treatment of this fatal disease is limited to chemotherapy using benzimidazoles and surgical intervention, with frequent disease recurrence in cases without radical surgery. Elucidating the molecular mechanisms underlying E. multilocularis infections and host-parasite interactions ultimately aids developing novel therapeutic options. This study explored an involvement of unfolded protein response (UPR) and endoplasmic reticulum-stress (ERS) during E. multilocularis infection in mice. Methods E. multilocularis- and mock-infected C57BL/6 mice were subdivided into vehicle, albendazole (ABZ) and anti-programmed death ligand 1 (αPD-L1) treated groups. To mimic a chronic infection, treatments of mice started six weeks post i.p. infection and continued for another eight weeks. Liver tissue was then collected to examine inflammatory cytokines and the expression of UPR- and ERS-related genes. Results E. multilocularis infection led to an upregulation of UPR- and ERS-related proteins in the liver, including ATF6, CHOP, GRP78, ERp72, H6PD and calreticulin, whilst PERK and its target eIF2α were not affected, and IRE1α and ATF4 were downregulated. ABZ treatment in E. multilocularis infected mice reversed, or at least tended to reverse, these protein expression changes to levels seen in mock-infected mice. Furthermore, ABZ treatment reversed the elevated levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and interferon (IFN)-γ in the liver of infected mice. Similar to ABZ, αPD-L1 immune-treatment tended to reverse the increased CHOP and decreased ATF4 and IRE1α expression levels. Conclusions and significance AE caused chronic inflammation, UPR activation and ERS in mice. The E. multilocularis-induced inflammation and consecutive ERS was ameliorated by ABZ and αPD-L1 treatment, indicating their effectiveness to inhibit parasite proliferation and downregulate its activity status. Neither ABZ nor αPD-L1 themselves affected UPR in control mice. Further research is needed to elucidate the link between inflammation, UPR and ERS, and if these pathways offer potential for improved therapies of patients with AE.

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Section: Introductionmentioning

confidence: 99%

Albendazole reduces hepatic inflammation and endoplasmic reticulum-stress in a mouse model of chronic Echinococcus multilocularis infection

et al. 2022

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“…If lesions cannot be completely removed by surgery, a lifelong medication is required, usually using benzimidazoles, which can cause adverse side effects. For example, several cases with hepatotoxic effects due to treatment with the benzimidazole albendazole (ABZ) were reported with various outcomes [11-14]. An inadequate adherence to chemotherapy, due to adverse side effects, can explain the relapsing spread of AE and a worsening general condition of patients with severe E. multilocularis infiltrations [15, 16].…”

Section: Introductionmentioning

confidence: 99%

Albendazole reduces endoplasmic reticulum stress induced byEchinococcus multilocularisin mice

Weingärtner

Jebbawi

et al. 2021

Preprint

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Background Echinococcus multilocularis causes alveolar echinococcosis (AE), a rising zoonotic disease in the northern hemisphere. Treatment of this fatal disease is limited to chemotherapy using benzimidazoles and surgical intervention, with relatively frequent disease recurrence in cases without radical surgery. Elucidating the molecular mechanisms underlying E. multilocularis infections and host-parasite interactions aids developing novel therapeutic options. This study explored an involvement of unfolded protein response (UPR) and endoplasmic reticulum-stress (ERS) during E. multilocularis infection in mice. Methods E. multilocularis- and mock-infected C57BL/6 mice were subdivided six weeks after infection into vehicle and albendazole (ABZ) treated groups. Eight weeks later, liver tissue was collected to examine mRNA, microRNA (miR) and protein expression of UPR- and ERS-related genes. Results E. multilocularis infection upregulated UPR- and ERS-related proteins, including ATF6, CHOP, GRP78, ERP72, H6PD and calreticulin, whilst PERK and its target eIF2α were not affected, and IRE1α and ATF4 were downregulated. ABZ treatment in E. multilocularis infected mice reversed the increased ATF6 and calreticulin protein expression, tended to reverse increased CHOP, GRP78, ERP72 and H6PD expression, and decreased ATF4 and IRE1α expression to levels seen in mock-infected mice. The expression of miR-146a-5p (downregulated by IRE1α) and miR-1839-5p (exhibiting a unique target site in the IRE1α 3’UTR) were significantly increased in E. multilocularis infected mice, an effect reversed by ABZ treatment. Other miRs analyzed were not altered in E. multilocularis infected mice. Conclusions and Significance AE causes UPR activation and ERS in mice. The E. multilocularis -induced ERS was ameliorated by ABZ treatment, indicating its effectiveness to inhibit parasite proliferation and downregulate its activity status. ABZ itself did not affect UPR in control mice. Identified miR-146a-5p and miR-1839-5p might represent biomarkers of E. multilocularis infection. Modulation of UPR and ERS, in addition to ABZ administration, could be exploited to treat E. multilocularis infection.

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Acute Liver Failure Secondary to Albendazole: Defining Albendazoleʼs Role in the Management of Echinococcal Infection

Cited by 2 publications

References 0 publications

Albendazole reduces hepatic inflammation and endoplasmic reticulum-stress in a mouse model of chronic Echinococcus multilocularis infection

Albendazole reduces hepatic inflammation and endoplasmic reticulum-stress in a mouse model of chronic Echinococcus multilocularis infection

Albendazole reduces endoplasmic reticulum stress induced byEchinococcus multilocularisin mice

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