TY - JOUR
T1 - Curcumin attenuates diabetic nephropathy by inhibiting PKC-α and PKC-β1 activity in streptozotocin-induced type I diabetic rats
AU - Soetikno, Vivian
AU - Watanabe, Kenichi
AU - Sari, Flori R.
AU - Harima, Meilei
AU - Thandavarayan, Rajarajan A.
AU - Veeraveedu, Punniyakoti T.
AU - Arozal, Wawaimuli
AU - Sukumaran, Vijayakumar
AU - Lakshmanan, Arun Prasath
AU - Arumugam, Somasundaram
AU - Suzuki, Kenji
PY - 2011/11
Y1 - 2011/11
N2 - Scope: We hypothesized that curcumin, a potent anti-oxidant, might be beneficial in ameliorating the development of diabetic nephropathy through inhibition of PKC-α and PKC-β1 activity-ERK1/2 pathway. Methods and results: Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ) (55mg/kg) in rats. Three weeks after STZ injection, rats were divided into three groups, namely, normal, diabetic and diabetic treated with curcumin at 100mg/kg/day, p.o., for 8wk. At 11wk after STZ injection, diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine clearance, increased blood urea nitrogen (BUN) and proteinuria, marked increases in lipid peroxidation, NOX4 and p67phox and decrease in anti-oxidant enzyme. All of these abnormalities were significantly reversed by curcumin. Furthermore, the high-glucose-induced PKC-α and PKC-β1 activities and phosphorylated ERK1/2 was significantly diminished by curcumin. Curcumin also attenuated the expression of TGF-β1, CTGF, osteopontin, p300 and ECM proteins such as fibronectin and type IV collagen. The high-glucose-induced expression of VEGF and its receptor VEGF receptor II (flk-1) was also ameliorated by curcumin. Conclusion: These results prove that curcumin produces dual blockade of both PKC-α and PKC-β1 activities, which suggests that curcumin is a potential adjuvant therapy for the prevention and treatment of diabetic nephropathy.
AB - Scope: We hypothesized that curcumin, a potent anti-oxidant, might be beneficial in ameliorating the development of diabetic nephropathy through inhibition of PKC-α and PKC-β1 activity-ERK1/2 pathway. Methods and results: Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ) (55mg/kg) in rats. Three weeks after STZ injection, rats were divided into three groups, namely, normal, diabetic and diabetic treated with curcumin at 100mg/kg/day, p.o., for 8wk. At 11wk after STZ injection, diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine clearance, increased blood urea nitrogen (BUN) and proteinuria, marked increases in lipid peroxidation, NOX4 and p67phox and decrease in anti-oxidant enzyme. All of these abnormalities were significantly reversed by curcumin. Furthermore, the high-glucose-induced PKC-α and PKC-β1 activities and phosphorylated ERK1/2 was significantly diminished by curcumin. Curcumin also attenuated the expression of TGF-β1, CTGF, osteopontin, p300 and ECM proteins such as fibronectin and type IV collagen. The high-glucose-induced expression of VEGF and its receptor VEGF receptor II (flk-1) was also ameliorated by curcumin. Conclusion: These results prove that curcumin produces dual blockade of both PKC-α and PKC-β1 activities, which suggests that curcumin is a potential adjuvant therapy for the prevention and treatment of diabetic nephropathy.
KW - Curcumin
KW - Diabetic nephropathy
KW - Mitogen-activated protein kinase
KW - Oxidative stress
KW - Protein kinase C
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U2 - 10.1002/mnfr.201100080
DO - 10.1002/mnfr.201100080
M3 - Article
C2 - 22045654
AN - SCOPUS:80155194979
VL - 55
SP - 1655
EP - 1665
JO - Molecular Nutrition and Food Research
JF - Molecular Nutrition and Food Research
SN - 1613-4125
IS - 11
ER -