Doxycycline cotherapy with albendazole relieves neural function damage in C57BL/6 and BALB/c mice infected with Angiostrongylus cantonensis

Eny Sofiyatun; Kuang-Yao Chen; Chih-Jen Chou; Hsin-Chia Lee; Yi-An Day; Pei-Jui Chiang; Cheng-Hsun Chiu; Wei-June Chen; Kai-Yuan Jhan; Lian-Chen Wang

doi:10.1016/j.bj.2024.100727

Doxycycline cotherapy with albendazole relieves neural function damage in C57BL/6 and BALB/c mice infected with Angiostrongylus cantonensis

Biomed J. 2024 Apr 16:100727. doi: 10.1016/j.bj.2024.100727. Online ahead of print.

Authors

Affiliations

¹ Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan; Department of Environmental Health, Polytechnic College of Banjarnegara, Central Java, 53482, Indonesia.
² Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan; Department of Parasitology, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan; Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Taoyuan, 333, Taiwan.
³ Department of Parasitology, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan.
⁴ Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan.
⁵ School of Medicine, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan.
⁶ Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Taoyuan, 333, Taiwan.
⁷ Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan; Department of Parasitology, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan.
⁸ Department of Parasitology, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan. Electronic address: ed790101@hotmail.com.
⁹ Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan; Department of Parasitology, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan; Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Taoyuan, 333, Taiwan. Electronic address: wanglc@mail.cgu.edu.tw.

PMID: 38636898
DOI: 10.1016/j.bj.2024.100727

Abstract

Background: We investigated the effects of combination therapy albendazole and doxycycline in Angiostrongylus cantonensis-infected mice during early and late treatment.

Materials and methods: C57BL/6 and BALB/c mice were divided into five groups: (i) uninfected, (ii) infected with A. cantonensis, (iii) infected + 10 mg/kg albendazole, (iv) infected + 25mg/kg doxycycline, and (v) infected + 10 mg/kg albendazole + 25 mg/kg doxycycline. We administered drugs in both early treatments started at 7-day post infections (dpi) and late treatments (14 dpi) to A. cantonensis-infected C57BL/6 and BALB/c mice. To assess the impact of these treatments, we employed the Morris water maze test to evaluate spatial learning and memory abilities, and the rotarod test to measure motor coordination and balance in C57BL/6 mice. Additionally, we monitored the expression of the cytokine IL-33 and GFAP in the brain of these mice using western blot analysis.

Results: In this study, A. cantonensis infection was observed to cause extensive cerebral angiostrongyliasis in C57BL/6 mice. This condition significantly affected their spatial learning and memory abilities, as assessed by the Morris water maze test, as well as their motor coordination, which was evaluated using the rotarod test. Early treatment with albendazole led to favorable recovery outcomes. Both C57BL/6 and BALB/c mice express IL-33 and GFAP after co-therapy. The differences of levels and patterns of IL-33 and GFAP expression in mice may be influenced by the balance between pro-inflammatory and anti-inflammatory signals within the immune system.

Conclusions: Combination therapy with anthelmintics and antibiotics in the early stage of A. cantonensis infection, in C57BL/6 and BALB/c mice resulted in the death of parasites in the brain and reduced the subsequent neural function damage and slowed brain damage and neurobehavior impairment. This study suggests a more effective and novel treatment, and drug delivery method for brain lesions that can decrease the neurological damage of angiostrongyliasis patients.

Keywords: Angiostrongylus cantonensis; GFAP; IL33; Morris water maze test; albendazole; doxycycline; neurobehavior impairment; rotarod test.