Acute kidney injury (AKI) is a common and serious complication in hospitalized patients, particularly in intensive care settings, and drug-induced kidney injury accounts for a substantial proportion of cases. Among the culprits, cisplatin—a widely used chemotherapy agent—stands out because it accumulates in renal tubular epithelial cells and triggers inflammation, apoptosis, and oxidative stress, causing AKI in nearly 30% of recipients. Current management relies heavily on renal replacement therapy due to a lack of effective preventive medicines. In this context, a new study published in Pediatric Discovery offers preclinical evidence that an aqueous extract of Phyllanthus urinaria L (PU) may protect against cisplatin-induced AKI through multiple pathways.
Researchers at the Children's Hospital of Chongqing Medical University and affiliated laboratories in Chongqing, China, tested a PU aqueous extract in 24 male C57BL/6 mice with cisplatin-induced AKI. The experiment used three groups: control, cisplatin, and cisplatin plus PU. Mice received a single intraperitoneal injection of cisplatin at 20 mg/kg; the treatment group also received PU at 250 mg/kg by oral gavage on days 0–2, and kidney and blood samples were collected on day 4. All mice survived. The team combined biochemical assays, histology, quantitative polymerase chain reaction (qPCR), Western blot, and immunofluorescence to assess renal function, tissue damage, inflammatory cytokine expression, apoptosis-related proteins, and antioxidant pathways.
Cisplatin raised blood urea nitrogen (BUN) and serum creatinine (Scr) and disrupted tubular architecture, with inflammatory cell infiltration and increased neutrophil gelatinase-associated lipocalin (NGAL). PU significantly attenuated these changes. qPCR showed that cisplatin increased messenger RNA levels of Il1b, Il6, and Tnf, encoding interleukin-1β, interleukin-6, and tumor necrosis factor-α, while PU suppressed these responses. Western blot and immunofluorescence showed that PU lowered Bcl-2-associated X protein (Bax) and cleaved caspase-3 and raised B-cell leukemia/lymphoma 2 (Bcl-2), indicating less apoptosis. PU also reduced malondialdehyde, increased superoxide dismutase activity, and restored nuclear factor erythroid 2-related factor 2 (NRF2) and NAD(P)H:quinone oxidoreductase 1 (NQO1) expression, supporting stronger antioxidant defense. Histology showed more organized tubules in the PU group than in cisplatin-only mice.
The authors said the study provides a multi-pathway rationale for PU in cisplatin-induced AKI, rather than a single-target effect. They noted that the extract appeared to protect renal tubules by calming inflammatory signaling, limiting apoptotic cell death, and reinforcing NRF2/NQO1-linked antioxidant defenses. The findings, reported with DOI 10.1002/pdi3.70000, are encouraging but early. The next steps should define active compounds, optimize dosing, and test safety and efficacy in clinically relevant models before any patient use is considered. The authors described the findings as a foundation for translational work, not a clinical recommendation.
For patients receiving cisplatin, a nephroprotective adjunct could widen therapeutic options and reduce treatment interruptions, but PU is not ready for clinical use on the basis of this mouse study. The findings point to several research priorities: identify the constituents responsible for the effects, confirm target engagement in human cells or organoids, determine whether PU interferes with cisplatin's anticancer activity, and evaluate safety, dosing, and drug interactions. Such work would need to balance kidney protection with unchanged tumor killing. If those questions are addressed, PU could become a candidate for further development as a supportive therapy for cisplatin-associated kidney injury. The study therefore offers a preclinical lead, not a prescription.
