Bonn Lee

A real-life environment during pregnancy involves multiple and simultaneous exposures to toxic chemicals. Perinatal exposures to toxic chemicals have been reported to exert an inhibitory effect on mouse neural development and behaviors. However, the effect of combined exposures of organophosphate and nicotine has not been previously reported. In this study, we investigated whether a combined exposure of diazinon and nicotine can have a synergistic effect. The effects of the combined chemical exposure on cell viability and neuronal differentiation were examined using mouse Sox1-GFP cells. Additionally, mice were maternally administered 0.18 mg/kg diazinon, a no adverse effect level (NOAEL) dose, combined with 0.4, 1, and 2 mg/kg nicotine. Mice offspring underwent behavior tests to assess locomotor, depressive, cognitive, and social behaviors. Morphological change in the brain was investigated with immunolocalization. We revealed that the combined exposure to diazinon and nicotine can have a synergistic adverse effect in vitro. In addition, the chemical-treated mouse offspring showed abnormalities in motor learning, compulsive-like behaviors, spatial learning, and social interaction patterns. Moreover, 0.18 mg/kg diazinon and 2 mg/kg nicotine co-exposure resulted in an increase in tyrosine hydroxylase (TH)-positive dopaminergic neurons. Thus, the findings suggest that perinatal co-exposure to nicotine and diazinon can result in abnormal neurodevelopment and behavior, even at low-level administration.

Acute and Prolonged Effects of Anti-Malarial Drugs on Mitochondrial Respiration in Atrial Cardiomyocytes for Cardiac Safety EvaluationObjectives: Malaria is a global public health problem, causing significant morbidity and mortality, particularly in low and middle-income countries (LMICs). While mass drug administration (MDA) programs are central to elimination efforts, their effectiveness is limited by concerns over cardiotoxicity, resistance, and potential impacts on mitochondrial function. This study investigates the acute and prolonged effects of single and combination anti-malarial drugs on mitochondrial respiration in atrial cardiomyocytes. Methods: Human iPSC-derived atrial cardiomyocytes were treated with either single or combination anti-malarial drugs. Mitochondrial respiration was assessed using an extracellular flux analyser (Agilent Seahorse).Results: Treatment with mefloquine (MFQ) and its combinations reduced mitochondrial respiration, indicating impaired energy generation in cardiomyocytes. Prolonged exposure to halofantrine (HFN) significantly reduced maximal respiration and spare respiratory capacity, demonstrating compromised mitochondrial function. In contrast, acute and prolonged exposure to amodiaquine (AMD), artemether (ART), chloroquine (CQ), and piperaquine (PPQ) maintained mitochondrial function. While acute exposure to Ivermectin (IVM), an anti-parasitic drug used in malaria treatment programmes, did not affect mitochondrial health, prolonged exposure resulted in reduced coupling efficiency.Conclusions: These findings provide insights into the effects of anti-malarial drugs on mitochondrial function in cardiomyocytes. Further studies should aim to elucidate the molecular mechanisms underlying these drug-induced mitochondrial effects.Keywords: malaria, anti-malarial drugs, atrial cardiomyocytes, mitochondrial respiration