Background <p>Kidney disease represents a significant global health challenge that can lead to serious health complications. The chemotherapeutic agent ‘doxorubicin’ has nephrotoxic effects as an adverse effect. Ongoing research is focused on finding protective agents that can alleviate doxorubicin’s adverse effects and enhance treatment results. Recently, an iron-rifampicin complex has been developed, showing promising anticancer activity with improved safety compared to a conventional drug. This study aimed to evaluate the potential protective effects of this iron-rifampicin complex, which has not been previously explored, against doxorubicin-induced nephrotoxicity in mice.</p> Methods <p>Six groups of sixty male albino mice were used: Control, Nephrotoxicity (Neph), Neph+low dose of iron-rifampicin complex (0.071&#xa0;mg iron-rifampicin complex/kg), Neph+high dose of iron-rifampicin complex (0.107&#xa0;mg iron-rifampicin complex/kg), Complex control in high dose (0.107&#xa0;mg iron-rifampicin complex/kg), and Vehicle control. The following parameters were evaluated: body weight, kidney weight, kidney index, creatinine, urea, uric acid, sodium, potassium, calcium, phosphorus, malondialdehyde, nitric oxide, reduced glutathione, catalase, superoxide dismutase, glutathione peroxidase, and vascular endothelial growth factor (VEGF), along with kidney histopathology.</p> Results <p>Doxorubicin-induced nephrotoxicity led to a significant reduction (<i>p</i> &lt; 0.001) in body weight, kidney weight, kidney index, antioxidants, and VEGF, while increasing (<i>p</i> &lt; 0.001) minerals, malondialdehyde, nitric oxide, creatinine, urea, and uric acid, alongside worsened kidney architecture. The iron-rifampicin complex improved all these parameters (<i>p</i> &lt; 0.05), moving them closer to normal levels, particularly at the lower dosage, mainly by reducing oxidative stress and preserving VEGF.</p> Conclusion <p>In conclusion, we propose the iron-rifampicin complex as a potential candidate for nephroprotection against doxorubicin-induced nephrotoxicity, subject to further validation.</p>

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Complexed rifampicin with iron mitigates doxorubicin-induced nephrotoxicity

  • Omnia A. Basal,
  • Entsar A. Saad,
  • Rana R. El Sadda

摘要

Background

Kidney disease represents a significant global health challenge that can lead to serious health complications. The chemotherapeutic agent ‘doxorubicin’ has nephrotoxic effects as an adverse effect. Ongoing research is focused on finding protective agents that can alleviate doxorubicin’s adverse effects and enhance treatment results. Recently, an iron-rifampicin complex has been developed, showing promising anticancer activity with improved safety compared to a conventional drug. This study aimed to evaluate the potential protective effects of this iron-rifampicin complex, which has not been previously explored, against doxorubicin-induced nephrotoxicity in mice.

Methods

Six groups of sixty male albino mice were used: Control, Nephrotoxicity (Neph), Neph+low dose of iron-rifampicin complex (0.071 mg iron-rifampicin complex/kg), Neph+high dose of iron-rifampicin complex (0.107 mg iron-rifampicin complex/kg), Complex control in high dose (0.107 mg iron-rifampicin complex/kg), and Vehicle control. The following parameters were evaluated: body weight, kidney weight, kidney index, creatinine, urea, uric acid, sodium, potassium, calcium, phosphorus, malondialdehyde, nitric oxide, reduced glutathione, catalase, superoxide dismutase, glutathione peroxidase, and vascular endothelial growth factor (VEGF), along with kidney histopathology.

Results

Doxorubicin-induced nephrotoxicity led to a significant reduction (p < 0.001) in body weight, kidney weight, kidney index, antioxidants, and VEGF, while increasing (p < 0.001) minerals, malondialdehyde, nitric oxide, creatinine, urea, and uric acid, alongside worsened kidney architecture. The iron-rifampicin complex improved all these parameters (p < 0.05), moving them closer to normal levels, particularly at the lower dosage, mainly by reducing oxidative stress and preserving VEGF.

Conclusion

In conclusion, we propose the iron-rifampicin complex as a potential candidate for nephroprotection against doxorubicin-induced nephrotoxicity, subject to further validation.