Penehyclidine hydrochloride ameliorates renal ischemia reperfusion-stimulated lung injury in mice by activating Nrf2 signaling

Penehyclidine hydrochloride ameliorates renal ischemia reperfusion-stimulated lung injury in mice by activating Nrf2 signaling Qiang Yang Department of Anesthesiology, Cangzhou Central Hospital, Teaching Hospital of Tianjin Medical University, Cangzhou 061000, Hebei, China http://orcid.org/0000-0001-8662-126X Lei Li Physical Examination Center, Cangzhou Central Hospital, Teaching Hospital of Tianjin Medical University, Cangzhou 061000, Hebei, China http://orcid.org/0000-0002-2702-7444 Zhaohui Liu Department of Anesthesiology, Cangzhou Central Hospital, Teaching Hospital of Tianjin Medical University, Cangzhou 061000, Hebei, China http://orcid.org/0000-0002-4571-124X Chunlei Li Department of Anesthesiology, Cangzhou Central Hospital, Teaching Hospital of Tianjin Medical University, Cangzhou 061000, Hebei, China http://orcid.org/0000-0003-4017-6820 Lili Yu Department of Anesthesiology, Cangzhou Central Hospital, Teaching Hospital of Tianjin Medical University, Cangzhou 061000, Hebei, China http://orcid.org/0000-0002-1674-9898 Yulin Chang Department of Anesthesiology, Cangzhou Central Hospital, Teaching Hospital of Tianjin Medical University, Cangzhou 061000, Hebei, China http://orcid.org/0000-0002-4895-8651

Introduction: Penehyclidine hydrochloride (PHC) is an anticholinergic with anti-inflammatory and anti-oxidation activities. PHC displayed protectivity against renal ischemia reperfusion (RIR) injury. Nevertheless, the precise protectivity of PHC on RIR-induced lung injury remains unknown. Methods: We examined the effects of PHC on RIR-induced lung injury and investigated the underlying mechanism. We induced RIR in mice and administrated PHC to RIR mice. Kidney function was monitored by measuring the blood urea nitrogen (BUN) and creatinine level in serum. We evaluated the lung injury, myeloperoxidase (MPO) activity in lung, pro-inflammatory cytokine level, and oxidative markers in serum and lung tissues. We tested the expression level of nuclear factor erythroid 2-related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1) in lung of RIR mice after PHC treatment. Finally, we evaluated the effects of PHC in RIR Nrf2-/- mice. Results: PHC greatly downregulated the serum levels of BUN, creatinine, IL-6, NO, malondialdehyde (MDA), and matrix metalloproteinase-2. PHC also ameliorated the lung injury, decreased the MPO activity, and suppressed production of IL-6, TNF-α, IFN-γ, MDA, and O2-, while it promoted production of superoxide dismutase (SOD) and catalase (CAT) in lung. PHC improved the production of Nrf2 and HO-1. Conclusion: The protectivity of PHC was absent in Nrf2-/- mice. PHC ameliorated RIR-induced lung injury through Nrf2 pathway.
10 30 2021 10 30 2021 1 10.34172/crossmark_policy bi.tbzmed.ac.ir false Tabriz University of Medical Sciences Tabriz University of Medical Sciences 2020-09-04 2021-04-27 2021-10-30 10.34172/bi.2021.23401 20211201132259 https://bi.tbzmed.ac.ir/Inpress/bi-23401 https://bi.tbzmed.ac.ir/Inpress/bi-23401.pdf https://bi.tbzmed.ac.ir/Inpress/bi-23401.pdf https://bi.tbzmed.ac.ir/Inpress/bi-23401.pdf https://bi.tbzmed.ac.ir/Inpress/bi-23401.pdf https://bi.tbzmed.ac.ir/Inpress/bi-23401.pdf