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Published on: May 6, 2018
Possible Protective Effect of Diacerein on Doxorubicin-Induced Nephrotoxicity in Rats
Marwa M M Refaie1, Entesar F Amin1, Nashwa F El-Tahawy2
1Department of Pharmacology, Faculty of Medicine, El-Minia University, El-Minia 61111, Egypt.
Abstract:
Nephrotoxicity is one of the limiting factors for using doxorubicin (DOX). Interleukin 1 has major role in DOX-induced nephrotoxicity, so we investigated the effect of interleukin 1 receptor antagonist diacerein (DIA) on DOX-induced nephrotoxicity. DIA (25 and 50 mg/kg/day) was administered orally to rats for 15 days, in the presence or absence of nephrotoxicity induced by a single intraperitoneal injection of DOX (15 mg/kg) at the 11th day. We measured levels of serum urea, creatinine, renal reduced glutathione (GSH), malondialdehyde (MDA), total nitrites (NO x ), catalase, and superoxide dismutase (SOD). In addition, caspase-3, tumor necrosis factor alpha (TNFα), nuclear factor kappa B (NFκB) expressions, and renal histopathology were assessed. Our results showed that DOX-induced nephrotoxicity was ameliorated or reduced by both doses of DIA, but diacerein high dose (DHD) showed more improvement than diacerein low dose (DLD). This protective effect was manifested by significant improvement in all measured parameters compared to DOX treated group by using DHD. DLD showed significant improvement of creatinine, MDA, NO x , GSH, histopathology, and immunohistochemical parameters compared to DOX treated group.
Insights
Diacerein (DIA) protects against doxorubicin (DOX)-induced kidney damage by reducing oxidative stress and inflammation. A high dose of DIA demonstrated significant nephroprotective effects in a rat model.
Area of Science:
- Pharmacology
- Toxicology
- Nephrology
Background:
- Doxorubicin (DOX) chemotherapy is limited by dose-dependent nephrotoxicity.
- Interleukin-1 (IL-1) plays a critical role in the pathogenesis of DOX-induced kidney injury.
- Diacerein (DIA), an IL-1 receptor antagonist, is investigated for its potential nephroprotective properties.
Purpose of the Study:
- To evaluate the efficacy of diacerein (DIA) in mitigating doxorubicin (DOX)-induced nephrotoxicity in a rat model.
- To assess the impact of DIA on key biomarkers of kidney damage, oxidative stress, and inflammation.
Main Methods:
- Rats were administered doxorubicin (DOX) to induce nephrotoxicity.
- Diacerein (DIA) at low (25 mg/kg) and high (50 mg/kg) doses was administered orally for 15 days.
- Serum urea, creatinine, renal oxidative stress markers (GSH, MDA, NO x , catalase, SOD), inflammatory markers (caspase-3, TNFα, NFκB), and renal histopathology were analyzed.
Main Results:
- Both low and high doses of DIA significantly reduced DOX-induced nephrotoxicity.
- The high dose of DIA exhibited superior protective effects across all measured biochemical and histopathological parameters.
- Significant improvements in creatinine, MDA, NO x , GSH, and histopathology were observed with the low dose of DIA compared to the DOX-treated group.
Conclusions:
- Diacerein (DIA) demonstrates significant nephroprotective effects against doxorubicin (DOX)-induced kidney injury.
- The therapeutic benefit of DIA is dose-dependent, with higher doses providing more comprehensive protection.
- DIA ameliorates DOX nephrotoxicity by reducing oxidative stress and inflammatory responses, suggesting its potential as an adjunct therapy.
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