Aliskiren alleviates doxorubicin-induced nephrotoxicity by inhibiting oxidative stress and podocyte injury.
BACKGROUND
Doxorubicin (DXR) is one of the most effective and widely used anthracycline antibiotics. However, its clinical application is hampered by toxic effects in many organs. Nephrotoxicity is one of the major side effects of anthracycline antibiotics. This study was designed to investigate the possible protective effects of aliskiren (a direct renin inhibitor) in DXR-induced nephrotoxicity in rats.


METHODS
Wistar albino rats were intraperitoneally (ip) injected with DXR and renin activity, albumin, total protein, urea, creatinine levels in plasma and ultrastructural changes in podocytes were assessed.


RESULTS
Rats subjected to DXR administration had significant (p<0.01) increases in systolic blood pressure, plasma renin activity, plasma concentration of urea, creatinine and tissue malondialdehyde and significant (p<0.01) reductions in plasma concentrations of albumin, total protein and antioxidant defense (reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT)) in renal tissues. Furthermore, DXR-induced nephrotoxicity has also been characterized by broadening of podocyte foot processes, enlargement of glomerular basement membrane width and reduction in slit pore diameter. The above effects of DXR were significantly (p<0.01) prevented by aliskiren treatment.


CONCLUSIONS
These findings revealed that the blockade of renin activity by aliskiren is a promising approach in the treatment of DXR-induced nephrotoxicity.
Faculty of Pharmacy, Jamia Hamdard (Hamdard University), India.
Azhar
A
Rashikh
Krishna K
KK
Pillai
Shibli J
SJ
Ahmad
Mohammad
M
Akhtar
Abul K
AK
Najmi
D000577:Amides / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001562:Benzimidazoles / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D004317:Doxorubicin / Q000009:adverse effects*; D005650:Fumarates / Q000494:pharmacology / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D015227:Lipid Peroxidation / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D050199:Podocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood; D012709:Serum Albumin / Q000378:metabolism; D013599:Systole / Q000187:drug effects; D000077333:Telmisartan; D014508:Urea / Q000097:blood
D000577:Amides; D000975:Antioxidants; D001562:Benzimidazoles; D001565:Benzoates; D005650:Fumarates; D012709:Serum Albumin; C446481:aliskiren; D004317:Doxorubicin; D014508:Urea; D003404:Creatinine; D012083:Renin; D000077333:Telmisartan