SMTP-44D Attenuates Renal Inflammatory/Oxidative Dysfunction in a Mouse Model of Ischemia–Reperfusion-Induced Acute Kidney Injury
TL;DR
Functional and molecular findings suggest that SMTP-44D provides anti-inflammatory and antioxidant renoprotection, while evidence supporting structural protection is lacking in the pre-ischemic administration protocol.
Abstract
Acute kidney injury (AKI) is a critical clinical challenge for which effective pharmacological therapies remain limited. Inflammation and oxidative stress play central roles in its pathogenesis. Here, we investigated the effects of Stachybotrys microspora triprenyl phenol-44D (SMTP-44D), a soluble epoxide hydrolase inhibitor that, unlike its analog SMTP-7, lacks thrombolytic activity, in a mouse model of renal ischemia–reperfusion (I/R)-induced AKI. SMTP-44D was administered either during or prior to ischemia. SMTP-44D improved renal functional parameters, including blood urea nitrogen, serum creatinine, and fractional sodium excretion in both protocols, with a protocol-dependent difference in creatinine clearance. An attenuation of tubular morphological alterations was observed when SMTP-44D was administered during ischemia, whereas pre-ischemic administration failed to demonstrate apparent morphological improvement. Mechanistic analysis was conducted using the pre-ischemic administration protocol. Urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule 1 were significantly reduced. SMTP-44D also suppressed renal tumor necrosis factor alpha, interleukin-1 beta, and NADPH oxidase-1 levels. Collectively, these functional and molecular findings suggest that SMTP-44D provides anti-inflammatory and antioxidant renoprotection, while evidence supporting structural protection is lacking in the pre-ischemic administration protocol. SMTP-44D warrants further investigation as a potential therapeutic strategy for I/R-induced AKI.