Lycopene protects against acute kidney injury by suppressing PARP/NOTCH-mediated inflammation.

Abstract

Acute kidney injury (AKI) is a clinical syndrome caused by diverse etiologies. It is characterized by a rapid decline in renal function, marked increases in serum creatinine and urea nitrogen levels, and excessive recruitment of inflammatory cells. Although lycopene exhibits notable anti-inflammatory properties, its specific mechanism of action and therapeutic potential in AKI remains to be elucidated. PARP1, which plays a role in DNA repair, chromatin regulation, gene expression, ribosomal biogenesis, and mRNA metabolism, has been implicated in the progression of AKI. In this study, we aimed to investigate the protective effects of lycopene in AKI models and elucidate its underlying mechanisms, focusing on its anti-inflammatory effects and targeted inhibition of PARP1. The protective effects of lycopene were tested in two AKI mouse models established using male C57BL/6 J mice, following a single intraperitoneal injection of cisplatin or renal ischemia-reperfusion (IRI) for 40 min. Renal function, tubular injury, and inflammation were assessed. In addition, the renoprotective effects of lycopene were evaluated in cisplatin- and hypoxia-treated tubular epithelial cells. The mechanisms underlying these effects were explored using RNA sequencing. In vivo, lycopene substantially suppressed the increase in serum creatinine and blood urea nitrogen levels. Moreover, lycopene alleviated tubular damage, as shown by periodic acid-Schiff staining and molecular analysis of KIM-1. These anti-inflammatory effects were further confirmed in vitro. Mechanistically, RNA sequencing revealed that lycopene markedly suppressed the Notch pathway by targeting PARP1. Lycopene may serve as a potential therapeutic agent for AKI treatment via PARP1/Notch-dependent mechanisms.