Fasciola hepatica ‐Derived Proteins Shield the Heart From Type 2 Myocardial Infarction in Rats by Modulating Oxidative Stress and Inflammatory Imbalance: Insights Relevant to the Hygiene Hypothesis

Myocardial infarction (MI) remains a leading cause of mortality worldwide, with type 2 MI (T2MI) carrying a worse prognosis than type 1 MI (T1MI). The hygiene hypothesis suggests that reduced microbial exposure in sanitized environments contributes to immune dysregulation and inflammation-related diseases. While helminth therapy has shown potential in modulating the inflammatory responses in myocardial injury, its effects on oxidative stress remain underexplored. We hypothesize that Fasciola hepatica total protein extract (FhTE) attenuates myocardial injury in T2MI via immune modulation consistent with the hygiene hypothesis, affecting both inflammation and oxidative stress. To investigate this, male Wistar rats were pretreated with FhTE (2.5 mg/kg, intraperitoneally) daily for 6 days. MI was induced by subcutaneous isoproterenol (100 mg/kg) on days five and six. Electrocardiographic analysis 24 h post-final treatment revealed that FhTE pretreatment attenuated MI-induced changes. FhTE reduced cardiac hypertrophy and decreased serum cardiac injury markers. It enhanced antioxidant defense by increasing superoxide dismutase (SOD) and catalase (CAT) activities, lowering nitric oxide (NO) and malondialdehyde (MDA) levels, and modulating nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA levels. FhTE also reduced neutrophil and M1 macrophage activity, evidenced by decreased myeloperoxidase (MPO) levels and inducible nitric oxide synthase (iNOS) mRNA expression, and downregulated inflammatory cytokine genes (IL-1β, IL-6, TNF-⍺, and IL-33). FhTE demonstrates significant cardioprotective effects by modulating inflammation and oxidative stress, thereby preconditioning the myocardium against T2MI. These findings offer robust experimental support for the hygiene hypothesis in the context of ischemic heart disease, highlighting its potential for novel MI therapies.