Silymarin exacerbates p53-mediated tubular apoptosis in glycerol-induced acute kidney injury in rats.
OBJECTIVE
Silymarin is an herbal extract with antioxidant properties that can reduce oxidative stress-mediated injuries in murine models of liver, heart, and kidney diseases. Silymarin can also increase p53-mediated cellular apoptosis in vitro. We tested the effect of silymarin administration before glycerol-induced acute kidney injury (Gly-AKI) in rats.


METHODS
Renal function, tubular injury, oxidative stress, leukocytes infiltration, and renal expression of apoptosis regulating proteins (p53, p-p53, Bax, Bcl-2, survivin, and cleaved caspase-3) were evaluated 6 or 24 h after glycerol.


RESULTS
Silymarin exacerbated the renal impairment and tubular apoptosis but had no effect on tubular necrosis or renal leukocytes infiltration. Renal lipid and DNA peroxidation was increased after glycerol and silymarin did not reduce oxidative stress. Proteins p53, p-p53, and proapoptotic Bax were upregulated in Gly-AKI rats treated with silymarin, whereas anti-apoptotic Bcl-2 was reduced in this group. Cleaved caspase-3 was overexpressed in Gly-AKI rats, particularly when treated with silymarin. Survivin was less expressed in Gly-AKI than in controls, but this deficit was not aggravated by silymarin.


CONCLUSIONS
The persistence of oxidative stress, inflammatory reaction, and tubular necrosis, as well as exacerbation of p53-mediated tubular apoptosis, led to a more severe renal impairment in Gly-AKI rats treated with silymarin.
Homsi
Eduardo
E
Division of Nephrology, Department of Medicine, Faculty of Medical Sciences, State University of Campinas, 04014-012 São Paulo, Brazil. ehomsi@aclnet.com.br
de Brito
Silvano Machado
SM
Janino
Patrícia
P
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D005990:Glycerol; D007668:Kidney / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D007958:Leukocyte Count; D015227:Lipid Peroxidation; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012838:Silymarin / Q000494:pharmacology* / Q000627:therapeutic use; D012997:Solvents; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D020011:Protective Agents; D012838:Silymarin; D012997:Solvents; D016159:Tumor Suppressor Protein p53; D005990:Glycerol