Iron-rifampicin complex mitigates doxorubicin-induced kidney damage in mice by reducing oxidative stress

Kidney disease poses a significant global health challenge, often leading to severe complications. Doxorubicin, a potent chemotherapeutic agent, is unfortunately limited by its dose-dependent nephrotoxic effects, causing substantial kidney damage. Current research actively seeks protective agents to mitigate these adverse effects and enhance treatment outcomes without compromising anticancer efficacy. A novel iron-rifampicin complex has recently emerged, demonstrating promising anticancer activity with an improved safety profile compared to conventional rifampicin. This study uniquely investigated the previously unexplored potential of this complex to protect against doxorubicin-induced nephrotoxicity.

Researchers utilized sixty male albino mice, divided into six groups, to evaluate the protective effects of an iron-rifampicin complex against doxorubicin-induced nephrotoxicity. Nephrotoxicity was induced in several groups, while others served as control, vehicle control, or complex control. The intervention groups received either a low dose of iron-rifampicin complex (0.071 mg/kg) or a high dose of iron-rifampicin complex (0.107 mg/kg). Key parameters assessed included body weight, kidney weight, kidney index, and a comprehensive panel of renal function markers (creatinine, urea, uric acid, sodium, potassium, calcium, phosphorus). Additionally, oxidative stress markers (malondialdehyde, nitric oxide, reduced glutathione, catalase, superoxide dismutase, glutathione peroxidase) and vascular endothelial growth factor (VEGF) levels were measured, alongside detailed kidney histopathology to evaluate structural integrity.

Doxorubicin administration significantly impaired renal health, leading to a p < 0.001 reduction in body weight, kidney weight, kidney index, antioxidant levels, and VEGF. Concurrently, doxorubicin significantly increased (p < 0.001) mineral levels, malondialdehyde, nitric oxide, creatinine, urea, and uric acid, while severely worsening kidney architecture. The iron-rifampicin complex demonstrated substantial protective effects, improving all these measured parameters significantly (p < 0.05), bringing them closer to normal physiological levels. This protective action was particularly pronounced at the lower dosage of 0.071 mg/kg. The primary mechanisms identified for this renoprotection included a marked reduction in oxidative stress and the preservation of VEGF levels.

The iron-rifampicin complex improved all doxorubicin-induced nephrotoxicity parameters (p < 0.05), with the 0.071 mg/kg dose showing superior efficacy, mainly by reducing oxidative stress and preserving VEGF.