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Salvianolic acid A as a multifunctional agent ameliorates doxorubicin-induced nephropathy in rats.

Fan HY, Yang MY, Qi D, Zhang ZK, Zhu L, Shang-Guan XX, Liu K, Xu H, Che X - Sci Rep (2015)

Bottom Line: Evidence suggest that multidrug therapy has more effect than monotherapy in amelioration of renal injury.Results revealed that treatment with SAA alleviated histological damages, relieved proteinuria, hypoalbuminemia and hyperlipidemia, reduced oxidative stress, as well as improving hemorheology.The anti-inflammation, antioxidant, amelioration of podocyte injury, improvement of hemorheology and hypolipidemic properties may constituent an important part of its therapeutic effects.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Yantai University, 264005 Yantai, Shandong Province, China.

ABSTRACT
Nephrotic syndrome (NS) is still a therapeutic challenge. To date there is no ideal treatment. Evidence suggest that multidrug therapy has more effect than monotherapy in amelioration of renal injury. Salvianolic acid A (SAA) is the major active component of Salviae Miltiorrhizae Bunge. Previous studies have demonstrated that SAA is a multi-target agent and has various pharmacological activities. The pleiotropic properties of SAA predict its potential in the treatment of NS. The study investigated the effect of SAA on doxorubicin-induced nephropathy. The kidney function related-biochemical changes, hemorheological parameters and oxidative stress status were determined, and histological examination using light and transmission electron microcopies and western blot analysis were also performed. Results revealed that treatment with SAA alleviated histological damages, relieved proteinuria, hypoalbuminemia and hyperlipidemia, reduced oxidative stress, as well as improving hemorheology. Furthermore, SAA restored podocin expression, down-regulated the expression of NF-κB p65 and p-IκBα while up-regulating IκBα protein expression. Overall, as a multifunctional agent, SAA has a favorable renoprotection in doxorubicin-induced nephropathy. The anti-inflammation, antioxidant, amelioration of podocyte injury, improvement of hemorheology and hypolipidemic properties may constituent an important part of its therapeutic effects. All these indicate that SAA is likely to be a promising agent for NS.

No MeSH data available.


Related in: MedlinePlus

The effect of SAA on urinary protein excretion at each time point.Rats were treated intravenously with SAA at doses of 2.5, 5, and 10 mg/kg or oral administration of prednisone acetate 10 mg/kg after doxorubicin (7.5 mg/kg) injection. Urine was collected for determination of proteinuria on days 3, 7, 14, 21 and 28 after DOX administration. Data are expressed as mean ± SD (n = 5). #P < 0.05, ##P < 0.01 vs. Control; *P < 0.05, **P < 0.01 vs. DOX alone. SAA, Salvianolic acid A; DOX, Doxorubicin.
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f1: The effect of SAA on urinary protein excretion at each time point.Rats were treated intravenously with SAA at doses of 2.5, 5, and 10 mg/kg or oral administration of prednisone acetate 10 mg/kg after doxorubicin (7.5 mg/kg) injection. Urine was collected for determination of proteinuria on days 3, 7, 14, 21 and 28 after DOX administration. Data are expressed as mean ± SD (n = 5). #P < 0.05, ##P < 0.01 vs. Control; *P < 0.05, **P < 0.01 vs. DOX alone. SAA, Salvianolic acid A; DOX, Doxorubicin.

Mentions: As shown in Fig. 1, 24 h urinary protein excretion of rats progressively increased after injection of DOX. On day 7, the urinary protein of DOX-treated rats was significantly higher than that of control rats (P = 0.016). Beginning on day 14, the urinary protein of DOX-treated rats rapidly increased (P = 0.001). Treatment with prednisone acetate significantly decreased urinary protein at 2, 3, and 4 weeks (P = 0.034, P = 0.000 and P = 0.000, respectively). SAA also decreased urinary protein. The effect was significant at doses of 5 and 10 mg/kg at 3 and 4 weeks (P = 0.000, P = 0.004 and P = 0.001, respectively). SAA 5 mg/kg markedly decreased urinary protein only at 3 weeks (P = 0.000), and had no notable effect at 2 and 4 weeks.


Salvianolic acid A as a multifunctional agent ameliorates doxorubicin-induced nephropathy in rats.

Fan HY, Yang MY, Qi D, Zhang ZK, Zhu L, Shang-Guan XX, Liu K, Xu H, Che X - Sci Rep (2015)

The effect of SAA on urinary protein excretion at each time point.Rats were treated intravenously with SAA at doses of 2.5, 5, and 10 mg/kg or oral administration of prednisone acetate 10 mg/kg after doxorubicin (7.5 mg/kg) injection. Urine was collected for determination of proteinuria on days 3, 7, 14, 21 and 28 after DOX administration. Data are expressed as mean ± SD (n = 5). #P < 0.05, ##P < 0.01 vs. Control; *P < 0.05, **P < 0.01 vs. DOX alone. SAA, Salvianolic acid A; DOX, Doxorubicin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4508635&req=5

f1: The effect of SAA on urinary protein excretion at each time point.Rats were treated intravenously with SAA at doses of 2.5, 5, and 10 mg/kg or oral administration of prednisone acetate 10 mg/kg after doxorubicin (7.5 mg/kg) injection. Urine was collected for determination of proteinuria on days 3, 7, 14, 21 and 28 after DOX administration. Data are expressed as mean ± SD (n = 5). #P < 0.05, ##P < 0.01 vs. Control; *P < 0.05, **P < 0.01 vs. DOX alone. SAA, Salvianolic acid A; DOX, Doxorubicin.
Mentions: As shown in Fig. 1, 24 h urinary protein excretion of rats progressively increased after injection of DOX. On day 7, the urinary protein of DOX-treated rats was significantly higher than that of control rats (P = 0.016). Beginning on day 14, the urinary protein of DOX-treated rats rapidly increased (P = 0.001). Treatment with prednisone acetate significantly decreased urinary protein at 2, 3, and 4 weeks (P = 0.034, P = 0.000 and P = 0.000, respectively). SAA also decreased urinary protein. The effect was significant at doses of 5 and 10 mg/kg at 3 and 4 weeks (P = 0.000, P = 0.004 and P = 0.001, respectively). SAA 5 mg/kg markedly decreased urinary protein only at 3 weeks (P = 0.000), and had no notable effect at 2 and 4 weeks.

Bottom Line: Evidence suggest that multidrug therapy has more effect than monotherapy in amelioration of renal injury.Results revealed that treatment with SAA alleviated histological damages, relieved proteinuria, hypoalbuminemia and hyperlipidemia, reduced oxidative stress, as well as improving hemorheology.The anti-inflammation, antioxidant, amelioration of podocyte injury, improvement of hemorheology and hypolipidemic properties may constituent an important part of its therapeutic effects.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Yantai University, 264005 Yantai, Shandong Province, China.

ABSTRACT
Nephrotic syndrome (NS) is still a therapeutic challenge. To date there is no ideal treatment. Evidence suggest that multidrug therapy has more effect than monotherapy in amelioration of renal injury. Salvianolic acid A (SAA) is the major active component of Salviae Miltiorrhizae Bunge. Previous studies have demonstrated that SAA is a multi-target agent and has various pharmacological activities. The pleiotropic properties of SAA predict its potential in the treatment of NS. The study investigated the effect of SAA on doxorubicin-induced nephropathy. The kidney function related-biochemical changes, hemorheological parameters and oxidative stress status were determined, and histological examination using light and transmission electron microcopies and western blot analysis were also performed. Results revealed that treatment with SAA alleviated histological damages, relieved proteinuria, hypoalbuminemia and hyperlipidemia, reduced oxidative stress, as well as improving hemorheology. Furthermore, SAA restored podocin expression, down-regulated the expression of NF-κB p65 and p-IκBα while up-regulating IκBα protein expression. Overall, as a multifunctional agent, SAA has a favorable renoprotection in doxorubicin-induced nephropathy. The anti-inflammation, antioxidant, amelioration of podocyte injury, improvement of hemorheology and hypolipidemic properties may constituent an important part of its therapeutic effects. All these indicate that SAA is likely to be a promising agent for NS.

No MeSH data available.


Related in: MedlinePlus