Effects of albendazole combined with TSII-A (a Chinese herb compound) on optic neuritis caused by Angiostrongylus cantonensis in BALB/c mice

Abstract

BackgroundAngiostrongylus cantonensis (A. cantonensis) infection can lead to optic neuritis, retinal inflammation, damage to ganglion cells, demyelination of optic nerve and visual impairment. Combined therapy of albendazole and dexamethasone is a common treatment for the disease in the clinic, but it plays no role in vision recovery. Therefore, it has been necessary to explore alternative therapies to treat this disease. Previous studies reported the neuro-productive effects of two constituents of Danshen (a Chinese herb)-tanshinone II-A (TSII-A) and cryptotanshinone (CPT), and this study aims to evaluate the impacts of TSII-A or CPT combined with albendazole on optic neuritis caused by A. cantonensis infection in a murine model.MethodsTo assess the effects of TSII-A or CPT combined with albendazole on optic neuritis due to the infection, mice were divided into six groups, including the normal control group, infection group and four treatment groups (albendazole group, albendazole combined with dexamethasone group, albendazole combined with CPT group and albendazole combined with TSII-A group). The infection group and treatment groups were infected with A. cantonensisand the treatment groups received interventions from 14 dpi (days post infection), respectively. At 21 dpi, the visual acuity of mice in each group was examined by visual evoked potential (VEP). The pathologic alteration of the retina and optic nerve were observed by hematoxylin and eosin (H&E) staining and transmission electronic microscopy (TEM).ResultsInfection of A. cantonensis caused prolonged VEP latency, obvious inflammatory cell infiltration in the retina, damaged retinal ganglions and retinal swelling, followed by optic nerve fibre demyelination and a decreasing number of axons at 21 dpi. In treatment groups, albendazole could not alleviate the above symptoms; albendazole combined with dexamethasone lessened the inflammation of the retina, but was futile for the other changes; however, albendazole combined with CPT and albendazole combined with TSII-A showed obvious effects on the recovery of prolonged VEP latency, destruction and reduction of ganglion cells, optic nerve demyelination and axon loss. Compared with albendazole-CPT compound, albendazole combined with TSII-A was more effective.ConclusionsThe current study demonstrates that albendazole combined with TSII-A plays a more effective role in treating optic neuritis caused by A. cantonensis in mice than with dexamethasone, as applied in conventional treatment, indicating that albendazole combined with TSII-A might be an alternate therapy for this parasitic disease in the clinic.

Angiostrongylus cantonensis: a review of its distribution, molecular biology and clinical significance as a human pathogen

“…Lai et al (2005 a ) used albendazole in combination with GM6001 (a matrix MMP-9 inhibitor) to reduce AEM severity in mice. In combination with albendazole, certain Chinese herbs and their extracts exhibited some beneficial effects in mouse models of Angiostrongylus optic neuritis and AEM (Lai, 2006; Feng et al 2015). Ginger extracts possess some activity against A. cantonensis (Lin et al 2010).…”

Inhibiting Interleukin 17 Can Ameliorate the Demyelination Caused by A. cantonensis via iNOS Inhibition

“…A. cantonensis is a parasitic nematode from rats which invades the central nerve system (CNS) and causes eosinophilic encephalitis or meningoencephalitis [ 2 ]. During this process, neurons in CNS appear with obvious demyelination [ 3 – 5 ] (MBP is one component of myelin sheath) [ 6 ]. However, the reason for demyelination associated with A. cantonensis infection has not been fully known.…”

Interleukin 17-producing γδ T cell induced demyelination of brain during Angiostrongylus cantonensis infection

“…Brain is the most severely damaged organ caused by the infection with A. cantonensis, whose related theory was various, but no one can fully explain the causes of death for this animal disease model [3,26]. Eosinophils infiltration, as the most outstanding characteristics, has long been studied, [27] where better prognosis was got through anti-inflammatory drug combination than using antiparasitic drugs alone.…”