Document Type : Original Article
Authors
1
Central Chest Institute of Thailand (CCIT), Department of Medical Services, Minister of Public Health, Nonthaburi, Thailand.
2
Interdisciplinary Program in genetic Engineering and Bioinformatics, Graduate School, Kasetsart University, Bangkok, Thailand.
3
Department of Biochemistry, Faculty of Science, Kasetsart University, Bangkok, Thailand.
4
Center for Advanced Studies in Nanotechnology for Chemical, Food and Agricultural Industries, KU Institute for Advanced Studies, Kasetsart University, Bangkok, Thailand.
5
Department of Biotechnology, Faculty of Applied Science, King Mongkut’s University of Technology North Bangkok, Bangkok, Thailand.
6
Food and Agro-Industrial Research Center, King Mongkut’s University of Technology North Bangkok, Bangkok, Thailand.
Abstract
Seeking a new drug has become a significant milestone in drug discovery. However, it might not be immediately used
in urgent situations or during a pandemic. Acute Respiratory Distress Syndrome (ARDS) contributes to mild-to-severe
symptoms in patients due to cytokine storms, leading to morbidity and mortality. Hypertension is recognized as an
independent risk factor for the severity of ARDS regarding to both ACE Inhibitors (ACEIs) and Angiotensin Receptor
Blockers (ARBs) treatment, although the precise mechanism remains unclear. In this study, murine macrophage cell
lines (RAW264.7) and alveolar epithelial type II-like cell lines (A549) were utilized to investigate the effect of Losartan
(LOS). LOS attenuated nitric oxide production in a dose-dependent manner and collectively reduced intracellular
reactive oxygen species (ROS) compared to Diclofenac under LPS-stimulation conditions. For ADRS-mimicking
conditions, LPS-induced inflammatory A549 cells were performed to monitor the effect of LOS. The results showed
that LOS exhibited a protective effect by increasing cell viability and decreasing intracellular ROS levels. Notably, a
high dose of LOS increased intracellular ROS levels. Moreover, LOS treatment downregulated NF-kappaB activation
and AT1R at the protein level. Correspondingly, proinflammatory mediator cytokines (TNF-alpha and IL-8) were
downregulated, but not IL-6, during LOS treatment. Hence, LOS may provide substantial benefits to ARDS patients
by modulating proinflammatory cytokine production through AT1R downregulation and NF-kappaB inactivation. The
mechanistic insight into LOS’s anti-inflammatory effect holds promise for reducing mortality rates among ARDS
patients.
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