Combination therapy with 3-Hydroxybenzaldehyde and Albendazole modulates mitochondrial protein expression in astrocytes after Angiostrongylus cantonensis infection

Background Angiostrongylus cantonensis is a zoonotic nematode that causes eosinophilic meningitis and central nervous system injury in humans; 3-hydroxybenzaldehyde (3-HBA) is a benzaldehyde compound that exhibits antioxidant and anti-inflammatory activities. Brain injury promotes Ca²⁺ influx and mitochondrial Ca²⁺ loading via voltage-dependent anion channel 1 (VDAC1) and the mitochondrial Ca²⁺ uniporter (MCU), leading to mitochondrial dysfunction and cytochrome c-mediated apoptosis. Methodology/Principal Findings This study aimed to evaluate the therapeutic effects of 3-HBA combined with albendazole on brain injury and the expression of mitochondria-related molecules in A. cantonensis -infected mice. In BALB/c mice infected with A. cantonensis , the infection significantly increased glial fibrillary acidic protein expression in five regions: the cerebral cortex, hippocampus, subcortical areas, cerebellum, and brainstem and elevated the expression of MCU and cytochrome c in the cerebral cortex and hippocampus. Hematoxylin and eosin staining revealed pathological changes, such as meningitis, hemorrhage, and vascular congestion. However, combined treatment with 3-HBA and albendazole reduced these pathological changes and the expression of mitochondria-related molecules, including glial fibrillary acidic protein, VDAC1, MCU, and cytochrome c. In cultured mouse astrocytes, soluble antigens from fifth-stage larval-activated astrocytes induced mitochondria-related molecule expression, but 3-HBA suppressed these effects. Conclusions/Significance These results suggest that the combination of 3-HBA and albendazole downregulates astrocyte activation and VDAC1/MCU-associated mitochondrial pathways following A. cantonensis infection. These findings support the use of 3-HBA as a promising adjuvant to albendazole in the treatment of angiostrongyliasis.