期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 23, 页码 -出版社
MDPI
DOI: 10.3390/ijms232314570
关键词
nephrotoxicity; doxorubicin; adrenomedullin; pyroptosis; gasdermin
This study showed that adrenomedullin (ADM) administration could protect against doxorubicin (DOX)-induced nephrotoxicity in rats. The protective effects of ADM may be attributed to its antioxidant, anti-inflammatory, anti-apoptotic, and anti-pyroptotic properties.
Doxorubicin (DOX) is an anticancer antibiotic which has various effects in human cancers. It is one of the commonly known causes of drug-induced nephrotoxicity, which results in acute renal injury. Adrenomedullin (ADM), a vasodilator peptide, is widely distributed in many tissues and has potent protective effects. Therefore, the current study aimed to examine the protective potential mechanisms of ADM against DOX-induced nephrotoxicity. A total of 28 male Wistar rats were randomized into four groups: control group, doxorubicin group (15 mg/kg single intraperitoneal injection of DOX), adrenomedullin + doxorubicin group (12 mu g/kg/day intraperitoneal injection of ADM) 3 days prior to DOX injection and continuing for 14 days after the model was established, and adrenomedullin group. Kidney function biomarkers, oxidative stress markers, and inflammatory mediators (TNF-alpha, NLRP3, IL-1 beta, and IL-18) were assessed. The expressions of gasdermin D and ASC were assessed by real-time PCR. Furthermore, the abundances of caspase-1 (p20), Bcl-2, and Bax immunoreactivity were evaluated. ADM administration improved the biochemical parameters of DOX-induced nephrotoxicity, significantly reduced oxidative damage markers and inflammatory mediators, and suppressed both apoptosis and pyroptosis. These results were confirmed by the histopathological findings and revealed that ADM's antioxidant, anti-inflammatory, anti-apoptotic, and anti-pyroptotic properties may have prospective applications in the amelioration of DOX-induced nephrotoxicity.
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