Protective effect of captopril, olmesartan, melatonin and compound 21 on doxorubicin-induced nephrotoxicity in rats

Area of Science:

• Nephrology
• Pharmacology
• Toxicology

Background:

• Chronic kidney disease (CKD) is a growing global health concern.
• Novel strategies for renal protection are crucial.
• Doxorubicin-induced nephrotoxicity serves as a model for studying kidney damage.

Purpose of the Study:

• To compare the renoprotective effects of melatonin and angiotensin II type 2 receptor agonist compound 21 (C21).
• To evaluate these agents against established drugs: angiotensin converting enzyme inhibitor captopril and angiotensin II type 1 receptor blocker olmesartan.
• To assess their efficacy in an animal model of doxorubicin nephrotoxicity.

Main Methods:

• Six groups of Wistar rats were treated for four weeks.
• Doxorubicin was administered to induce nephrotoxicity.
• Treatment groups received vehicle, captopril, olmesartan, melatonin, or C21.
• Blood pressure, oxidative stress, glomerular density, and size were measured.

Main Results:

• Doxorubicin increased blood pressure and oxidative stress, while reducing glomerular density and increasing size.
• Captopril, olmesartan, and melatonin attenuated the rise in systolic blood pressure.
• All four tested substances (captopril, olmesartan, melatonin, C21) significantly reduced oxidative stress.
• These agents prevented glomerular density reduction and partially prevented glomerular size increase.

Conclusions:

• Captopril, olmesartan, melatonin, and C21 demonstrated comparable renoprotective effects.
• These findings highlight potential therapeutic benefits of melatonin and C21 in mitigating kidney damage.