Protective Effects of SPA0355, a Thiourea Analogue, Against Lipopolysaccharide-Induced Acute Kidney Injury in Mice

Abstract

<jats:p>Inflammation and oxidative stress plays an essential role in the pathophysiology of sepsis-associated acute kidney injury (AKI). SPA0355, a thiourea analogue, has been shown to display beneficial effects against a variety of inflammatory diseases arising from its anti-inflammatory and anti-oxidant properties. However, the potential protective effects of SPA0355 against lipopolysaccharide (LPS)-induced AKI have not been explored. The aim of this study was to evaluate the effects of SPA0355 on LPS-induced AKI and investigate its underlying mechanisms. We found that renal dysfunction and histological abnormalities after LPS injection were significantly ameliorated by SPA0355. The compound also reduced renal expression of tubular injury markers. Mechanistically, SPA0355 significantly suppressed plasma and tissue levels of inflammatory cytokines and immune cell infiltration with inhibition of nuclear factor kappa-B p65 signaling. In addition, elevated levels of 4-hydroxynonenal and malondialdehyde after LPS injection were significantly decreased by SPA0355. The compound also regulated expression of pro-oxidant and antioxidant enzymes after LPS injection. Moreover, SPA0355 attenuated LPS-induced tubular cell apoptosis via inhibition of p53 signaling pathway. Altogether, these results suggest that SPA0355 protects against LPS-induced AKI through suppressing inflammation, oxidative stress, and tubular cell apoptosis and might be a potential preventive option for the disease.</jats:p>

Antioxidative, Antiapoptotic, and Anti-Inflammatory Effects of Apamin in a Murine Model of Lipopolysaccharide-Induced Acute Kidney Injury

“…In our study, LPS treatment increased the amounts of lipid peroxidation products and reversed a reduction in GSH/GSSG ratio in the kidneys. These results are consistent with previous studies showing that markedly elevated levels of ROS, protein oxidation, and lipid peroxidation were detected in patients with septic AKI [20,32] and mice injected with LPS [19,20]. Interestingly, we found that oxidative stress induced by LPS was effectively alleviated by apamin.…”

“…In addition, immune cell infiltration into injured kidneys has been known to aggravate inflammation and tissue injury [2,3]. Infiltration of multiple pro-inflammatory cells, such as macrophages and CD4 + T cells, is also commonly detected in the CLP sepsis model [39,42] and the LPS-induced AKI model [19,43]. Here, we showed that LPS-injected mice displayed increased expression of TLR4 compared to control mice.…”

“…Oxidative stress plays an important role in septic AKI [2,3]. Previous studies have shown that there is a marked increase in oxidative damage in LPS-induced renal injury [19,20]. Thus, we examined the effect of apamin on LPS-induced oxidative stress.…”

“…Apamin (0.1 mg/kg) was intraperitoneally administered to mice in the LPS + APM group 1 h after LPS injection. The doses of apamin and LPS used in the present study were chosen based on the results of previous studies [16,19]. At 24 h after LPS injection, all mice were sacrificed.…”

Inhibition of p300 by Garcinol Protects against Cisplatin-Induced Acute Kidney Injury through Suppression of Oxidative Stress, Inflammation, and Tubular Cell Death in Mice

“…Thin sections (4 μm) were stained with hematoxylin and eosin (H&E) or periodic acid–Schiff (PAS). The severity of tubular injury was scored semiquantitatively by estimating the percentage of damaged area: 0, 0%; 1, ≤10%; 2, 11–25%; 3, 26–45%; 4, 46–75%; and 5, 76–100% [ 32 , 33 ]. Tubular injury was analyzed in 5 randomly chosen fields at ×400 magnification per kidney sample.…”