Inhalation exposure to silver nanoparticles induces hepatic inflammation and oxidative stress, associated with altered renin‐angiotensin system signaling, in Wistar rats

Abstract

Silver nanoparticles (AgNPs) have become increasingly popular in the biomedical field over the last few decades due to its proven antibacterial property. Previous scientific studies have reported that one of the major organs responsible for detoxification of AgNPs is the liver. The liver is also the primary organ responsible for secretion of angiotensinogen (AGT), a key signaling molecule involved in the renin‐angiotensin system (RAS), which plays an important role in maintaining cardiac output and vascular pressure. The aim of this study was to assess any potential changes in the RAS‐associated gene signaling, inflammatory response, and hepatocellular toxicity resulting from AgNP exposure. To do this, 6‐week‐old, male Wistar rats were exposed to a subacute inhalation exposure of AgNP (200 ppb/days over 4 h/days exposure, for 5 d) and their livers were analyzed for alterations in RAS components, inflammation, and oxidative stress. Real time qPCR analysis showed that AgNP‐exposure resulted in a significant increase in hepatic AGT, angiotensin converting enzyme (ACE)‐1, and ACE‐2 mRNA expression. Expression of inflammatory markers interleukin (IL)‐6, IL‐1β, and tumor necrosis factor (TNF)‐α were also upregulated with AgNP‐exposure, compared to controls. Furthermore AgNP‐exposure mediated a significant increase in hepatic expression of catalase, and superoxide dismutase, and oxidative stress, as assessed via 8‐Oxo‐2′‐deoxyguanosine staining. Increased oxidative stress was associated with increased monocyte/macrophage‐2 staining in the liver of AgNP‐exposed rats. Such findings indicate that subacute inhalation exposure to AgNPs mediate increased hepatic RAS signaling, associated with inflammation, macrophage infiltration, and oxidative stress.

AgNPs Aggravated Hepatic Steatosis, Inflammation, Oxidative Stress, and Epigenetic Changes in Mice With NAFLD Induced by HFD

“…Li found that AgNPs, rather than silver ions, induced mitochondrial dynamics disorders, oxidative stress, and mitochondria-dependent hepatocyte apoptosis in mice ( Li et al, 2021 ). Recently scientific studies have demonstrated the hepatotoxic potential of AgNPs, such as histopathological hepatic lesions, oxidative stress, activation of inflammatory signaling, and pathological lipid peroxidation, when administrated in vivo in a dose-dependent manner ( Jia et al, 2017a ; Nayek et al, 2022 ). NAFLD is the leading cause of chronic liver disease worldwide with a 2-fold increase in the past 2 decades and afflicts approximately 30% of the general population and up to 95% of subjects with obesity and diabetes ( Eslam et al, 2018 ; Younossi et al, 2019 ).…”

“…AgNP-intoxication significantly disturbed liver function, elevated hepatic lipid peroxidation, increased liver DNA damage, and induced biochemical and histological alterations in rats ( Albrahim and Alonazi, 2020 ). Subacute exposure to AgNPs induces hepatic inflammation, macrophage infiltration, oxidative stress, and altered liver renin-angiotensin system signaling in Wistar rats ( Nayek et al, 2022 ). Mice intravenously injected with AgNPs had an increased prevalence of hepatocellular necrosis and gall bladder hemorrhage, especially in mice injected with 10 nm AgNPs ( Recordati et al, 2016 ).…”

“…Inflammatory responses in the liver will increase the risk of the development and progression of NAFLD ( Srinivas et al, 2021 ). Pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β, have been reported to be upregulated both in vitro and in vivo tests after AgNP exposure ( Nayek et al, 2022 ). Therefore, the potential hepatotoxicity of AgNPs on NAFLD development and progression should be of great concern.…”

Double-Sided Nano-ZnO: Superior Antibacterial Properties and Induced Hepatotoxicity in Zebrafish Embryos

“…wnt2bb and mypt1 play important roles in the formation phase of liver progenitor cells. They are essential molecules for liver development in zebrafish [ 32 ]. It was found that the expression level of wnt2bb and mypt1 decreased after exposure to Nano-ZnO, but there was no significant difference.…”

Catalpol ameliorates inflammation and oxidative stress via regulating Sirt1 and activating Nrf2/HO‐1 signaling against acute kidney injury

“…Clinical studies showed that oxidative stress and inflammation might play a crucial role in inducing multi-organ injury. [13][14][15][16][17][18][19][20] Recent pharmacological studies have revealed anti-apoptotic, antioxidant, and anti-inflammatory properties of Cat. [21][22][23] Moreover, Fu et al insinuated that Cat suppressed inflammation to mitigate acute lung injury in LPS-treated acute lung injury mice.…”