Acute carbon monoxide poisoning induces renal inflammation and apoptosis via CCL4 upregulation and activation of the PI3K/Akt pathway in mice.

Acute carbon monoxide poisoning (ACOP) is one of the primary causes of poisoning worldwide, leading to multi‑organ dysfunction, particularly affecting the kidneys. However, the molecular mechanisms underlying the effects of carbon monoxide‑induced acute kidney injury (AKI) remain yet to be fully elucidated. Therefore, the present study aimed to identify key genes and signaling pathways involved in AKI following ACOP in a mouse model using the RNA sequencing (RNA‑seq) technology. Renal function was assessed via measuring serum creatinine (SCr) and blood urea nitrogen (BUN) levels. Additionally, histopathological alterations, cell apoptosis and inflammation were evaluated by immunohistochemistry, TUNEL assay, ELISA and western blot analysis. The results revealed significant renal insufficiency and tubular injury, alongside a heightened inflammatory state and apoptosis in ACOP mice. RNA‑seq and mechanistic studies identified the upregulation of C‑C motif chemokine ligand 4 (CCL4) and activation of the PI3K/Akt pathway as key underlying events. Inhibition of PI3K with LY294002 attenuated these pathological changes and alleviated kidney injury. AKT In conclusion, the present study demonstrated that ACOP induced renal inflammation and apoptosis through CCL4 upregulation and activation of the PI3K/Akt pathway, thus conveying a potential therapeutic target for mitigating ACOP‑induced AKI (ACOP‑AKI). Overall, the present study could provide important insights into the molecular mechanisms of ACOP‑AKI.