Among the non-communicable neurological diseases, epilepsy is characterized by abnormal brain activity with several peripheral implications. The role of peripheral inflammation in the relationship between seizure development and nonalcoholic fatty liver disease based on sex difference remains still overlooked. Severe early-life infections lead to increased inflammation that can aggravate epilepsy and hepatic damage progression, both related to increased odds of hospitalization for epileptic patients with liver diseases. Here, we induced a post-natal-day 3 (PND3) infection by LPS (1 mg/kg, i.p.) to determine the hepatic damage in a genetic model of young epileptic WAG/Rij rats (PND45). We evaluated intra- and inter-gender differences in systemic and liver inflammation, hepatic lipid dysmetabolism, and oxidative damage related to mitochondrial functional impairment. First, epileptic rats exposed to LPS, regardless of gender, displayed increased serum hepatic enzymes and altered lipid profile. Endotoxin challenge triggered a more severe inflammatory and immune response in male epileptic rats, compared to females in both serum and liver, increasing pro-inflammatory cytokines and hepatic immune cell recruitment. Conversely, LPS-treated female rats showed significant alterations in systemic and hepatic lipid profiles and reduced mitochondrial fatty acid oxidation. The two different sex-dependent mechanisms of LPS-induced liver injury converge in increased ROS production and related mitochondrial oxidative damage in both sexes. Notably, a compensatory increase in antioxidant defense was evidenced only in female rats. Our study with a translational potential demonstrates, for the first time, that early post-natal infections in epileptic rats induced or worsened hepatic disorders in a sex-dependent manner, amplifying inflammation, lipid dysmetabolism, and mitochondrial impairment.

Epilepsy is a non-communicable neurological disease characterized by abnormal brain activity with conceivable peripheral implications. Few studies examine the role of peripheral and brain inflammation in the relationship between seizure predisposition and nonalcoholic fatty liver disease. Severe early-life infections leading to sepsis results in increased inflammation that can aggravate epilepsy and hepatic damage progression both associated with increased odds for hospital admissions in epileptic patients. Here, we examined the effect of early LPS challenge (1 mg/kg, i.p. at post-natal day3, PND3) in inducing hepatic damage in a genetic model of young epileptic WAG/Rij rats (PND45), evaluating the intra- and inter-gender differences on systemic and liver inflammation, hepatic lipid dysmetabolism and oxidative damage associated to mitochondrial functional impairment. First, epileptic rats exposed to LPS, regardless of gender, displayed increased serum hepatic enzymes and altered lipid profile. Early LPS challenge induced a major inflammatory and immune response in male epileptic rats than females in both serum and liver, increasing pro-inflammatory cytokines and hepatic immune cell recruitment. Conversely, LPS-insulted females showed a marked alteration in hepatic metabolic and lipid profile and the reduction in mitochondrial fatty acid oxidation. The two different gender-related mechanisms of LPS-induced liver injury converge in mitochondrial oxidative damage with intensified ROS production in both sexes, that notably induced a compensatory increase in antioxidant defense only in females. Our study with a translational potential points out that early postnatal infections predispose epileptic rats to develop or worsen hepatic disorders in a sex-dependent manner, amplifying inflammation, lipid dysmetabolism, and mitochondrial impairment.

Excessive reactive oxygen species (ROS) under pathophysiological conditions primarily initiate oxidative stress, which contributes to the development of atherosclerosis and other cardiovascular diseases. Hydrogen peroxide (H2O2) is a crucial oxidative stress biomarker due to its stability and significant role in signaling pathways linked to cellular damage. Hence, H₂O₂ detection is crucial for early disease diagnosis, understanding oxidative stress mechanisms, and therapeutic intervention, especially in cardiac health, where oxidative damage is significant. However, efficient, highly selective & sensitive, quick, and accurate H₂O₂ detection remains a challenge in the protracted battle against oxidative stress-related diseases. The study presents a fast, portable, low-cost, and versatile oxidative stress detection platform using a rGO-Co₃O₄-Pt nanocomposites electrochemical sensor platform, which can be remotely controlled. The sensors offer ultrasensitive, versatile cardiac stress monitoring, with H2O2 detection up to 2.50 µM, low LOD (0.16 µM) and LOQ (0.50 µM), with anti-interference capability and biocompatibility, indicating the possibility of real-sample analysis. Furthermore, we conducted studies on doxorubicin (DOX)-induced cardiotoxicity in vitro (HL-1 cell lines) and in vivo (adult C57BL/6J mice model). The study indicates that the rGO-Co₃O₄-Pt nanocomposite electrochemical sensor platform can efficiently and accurately detect diseases. This work provides direct experimental evidence of ROS detection and offers an efficient electronic platform that is significantly lighter, cheaper, and smaller than alternatives.