Acute kidney injury is common in hospitalized patients and rises sharply in intensive care, yet treatment options remain largely supportive. Drug-induced kidney injury accounts for a substantial share of cases, and cisplatin is a leading culprit: it accumulates in renal tubular epithelial cells and triggers inflammation, apoptosis and oxidative stress, causing acute kidney injury (AKI) in nearly 30% of recipients. Current management relies heavily on renal replacement therapy because effective preventive medicines are lacking. Natural products with antioxidant and anti-inflammatory activity have attracted interest, but evidence for Phyllanthus urinaria L (PU) in cisplatin nephrotoxicity is limited. Based on these challenges, or because of these issues, in-depth research is needed into PU as a nephroprotective candidate against cisplatin-induced AKI.
Researchers at the Children’s Hospital of Chongqing Medical University and affiliated laboratories in Chongqing, China, reported (DOI: 10.1002/pdi3.70000) the findings in Pediatric Discovery in 2025. The team tested a PU aqueous extract in 24 male C57BL/6 mice with cisplatin-induced AKI, combining biochemical assays, histology, quantitative polymerase chain reaction (qPCR), Western blot and immunofluorescence. The experimental model used a single high-dose cisplatin injection and oral PU treatment. The study examined renal function, tissue damage, inflammatory cytokine expression, apoptosis-related proteins and antioxidant pathways to assess whether PU could reduce cisplatin nephrotoxicity.
The experiment used three groups: control, cisplatin and cisplatin plus PU. Twenty-four male C57BL/6 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. 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 (mRNA) levels of Il1b, Il6 and Tnf, encoding interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-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 (MDA), increased superoxide dismutase (SOD) 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, and the antioxidant findings aligned with Western blot and immunofluorescence data for NRF2 and NQO1. These coordinated readouts link PU to anti-inflammatory, anti-apoptotic and antioxidant actions.
The authors said the study provides a multi-pathway rationale for PU in cisplatin-induced AKI, rather than a single-target effect. They said the extract appeared to protect renal tubules by calming inflammatory signaling, limiting apoptotic cell death and reinforcing NRF2/NQO1-linked antioxidant defenses. They also said the mouse data are encouraging but early, and that the next steps should define active compounds, optimize dosing and test safety and efficacy in clinically relevant models before any patient use is considered. They 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.