High efficacy of camphene and metronidazole combination therapy against Giardia lamblia infection in mice

Although synthetic antigiardial medications frequently exhibit efficacy, they may also result in negative side effects. Furthermore, issues related to drug resistance and the potential for mutagenic effects have been highlighted. The current research seeks to assess the combined anti-giardial efficacy of camphene (CP) both independently and in conjunction with metronidazole (MNZ) in the context of <i>Giardia lamblia</i> infection. The <i>in vitro</i> effectiveness of CP, both as alone treatment and in conjunction with MNZ, was assessed for its anti-giardial properties against both cysts and trophozoites of <i>G. lamblia</i> using a cell viability assay. Additionally, the effects of CP (100 mg/kg and 200 mg/kg), both alone and in combination with MNZ (5 mg/kg), were investigated. This assessment focused on the load and viability of cysts, serum electrolyte levels, adaptive-response cytokines (Interleukin-1 (IL-1) and IFN-γ), as well as the expression levels of apoptosis-related genes encoding the enzymes caspase-3, -8, and - 9. Both CP and the combination of CP with MNZ markedly increased the mortality of cyst and trophozoites (<i>p</i> < 0.001); indicating the existence of synergistic interactions when CP is co-administered with MNZ. CP alone and in the combination with MNZ significantly enhanced reactive oxygen species (ROS) production, while, downregulated the expression of the nicotinamide adenine dinucleotide oxidase (NADH), peroxiredoxin1a (PXR1a), and superoxide reductase (SOR) genes in <i>G. lamblia</i> trophozoites following (<i>p</i> < 0.001). By <i>in vivo</i>, the load and the viability of <i>G. lamblia</i> cysts excreted from the feces of infected mice, significantly modulated the serum electrolytes (<i>p</i> < 0.001), increased the serum levels of the cytokines IL-17 and IFN-γ (p < 0.001), and reduced the caspase-3, -8, and - 9 gene expression following a seven-day treatment with CP and CP + MNZ. Recent research has revealed hopeful effects of CP alone, particularly its synergistic interactions with MNZ against <i>G. lamblia</i> infection. Nevertheless, additional investigation is necessary to make clear the specific mechanisms and to evaluate its effectiveness in clinical trials, which could enhance the application of CP in the treatment and management of giardiasis.