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Induction of Nephrotic Syndrome in Mice by Retrobulbar Injection of Doxorubicin and Prevention of Volume Retention by Sustained Release Aprotinin
Published on: May 6, 2018
Adrenomedullin Mitigates Doxorubicin-Induced Nephrotoxicity in Rats: Role of Oxidative Stress, Inflammation,
Rania Nagi Abd-Ellatif1, Nahla Anas Nasef1, Hemat El-Sayed El-Horany1,2
1Medical Biochemistry Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt.
Abstract:
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 μg/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-α, NLRP3, IL-1β, 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.
Insights
Adrenomedullin (ADM) protects against doxorubicin (DOX)-induced kidney injury by reducing oxidative stress and inflammation. This study shows ADM
Area of Science:
- Nephrology
- Pharmacology
- Toxicology
Background:
- Doxorubicin (DOX) is a vital chemotherapy agent but causes significant nephrotoxicity.
- Drug-induced kidney injury is a critical clinical concern.
- Adrenomedullin (ADM) is a peptide hormone with known protective functions.
Purpose of the Study:
- To investigate the protective mechanisms of Adrenomedullin (ADM) against Doxorubicin (DOX)-induced nephrotoxicity.
- To evaluate ADM's effects on oxidative stress, inflammation, apoptosis, and pyroptosis in the context of DOX treatment.
Main Methods:
- A rat model of DOX-induced nephrotoxicity was established.
- Rats were treated with Adrenomedullin (ADM) prior to and after DOX administration.
- Kidney function, oxidative stress markers, inflammatory mediators (TNF-α, NLRP3, IL-1β, IL-18), and apoptosis/pyroptosis markers were assessed.
Main Results:
- ADM treatment significantly improved kidney function biomarkers compared to the DOX-only group.
- ADM administration markedly reduced markers of oxidative stress and inflammation.
- ADM suppressed both apoptosis and pyroptosis, as evidenced by molecular and histopathological analyses.
Conclusions:
- Adrenomedullin (ADM) demonstrates significant protective effects against Doxorubicin (DOX)-induced nephrotoxicity.
- ADM's benefits are attributed to its antioxidant, anti-inflammatory, anti-apoptotic, and anti-pyroptotic properties.
- ADM shows promise as a therapeutic agent to mitigate chemotherapy-induced kidney damage.
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