Diosgenin attenuates vascular calcification in chronic renal failure rats

Manivannan, Jeganathan; Barathkumar, T. R.; Sivasubramanian, J.; Arunagiri, P.; Raja, Boobalan; Balamurugan, Elumalai

doi:10.1007/s11010-013-1588-8

Cited by 38 publications

(29 citation statements)

References 40 publications

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“…Interestingly, Feere et al (2015) have shown that the liver histology was normal in an adenine-induced model of CKD, yet their data on the activity of two plasma enzymes, ALT and AST (measured as hepatic functions tests), indicated that the activities of these enzymes had been significantly inhibited four-and twofold, respectively, while the hepatic total CYP450 content was halved. Contrary to these data we have found, as well as others, that the activities of these plasma enzymes are elevated and not inhibited (Al Za'abi et al 2015, Kim et al 2013, Manivannan et al 2013. This probably indicates some tissue damage in the liver in adeninetreated rats, which is at variance with results obtained by Feere et al (2015).…”

Section: Discussioncontrasting

confidence: 93%

The In Vivo Effects of Adenine-Induced Chronic Kidney Disease on Some Renal and Hepatic Function and CYP450 Metabolizing Enzymes

Za’abi

Shalaby²,

Manoj

et al. 2017

Physiol Res

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Adenine-induced model of chronic kidney disease (CKD) is a widely used model especially in studies testing novel nephroprotective agents. We investigated the effects of adenine-induced CKD in rats on the activities of some xenobiotic metabolizing enzymes in liver and kidneys, and on some in vivo indicators of drug metabolism (viz pentobarbitone sleeping time, and plasma concentration of theophylline 90 min post administration). CKD was induced by orally feeding adenine (0.25 % w/w) for 35 days. Adenine induced all the characteristics of CKD, which was confirmed by biochemical and histological findings. Glutathione concentration and activities of some enzymes involved in its metabolism were reduced in kidneys and livers of rats with CKD. Renal CYP450 1A1 activity was significantly inhibited by adenine, but other measured isoenzymes (1A2, 3A4 and 2E1) were not significantly affected. Adenine significantly prolonged pentobarbitone-sleeping time and increased plasma theophylline concentration 90 min post administration. Adenine also induced a moderate degree of hepatic damages as indicated histologically and by significant elevations in some plasma enzymes. The results suggest that adenine-induced CKD is associated with significant in vivo inhibitory activities on some drug-metabolizing enzymes, with most of the effect on the kidneys rather than the liver.

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Section: Discussioncontrasting

confidence: 93%

The In Vivo Effects of Adenine-Induced Chronic Kidney Disease on Some Renal and Hepatic Function and CYP450 Metabolizing Enzymes

Za’abi

Shalaby²,

Manoj

et al. 2017

Physiol Res

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“…The protective effect of gemigliptin on VC was independent of the level of serum phosphorus. Similarly, a previous report showed that the protective effect of diosgenin against VC depends on the direct action on VSMCs regardless of blood chemistry [28]. …”

Section: Discussionmentioning

confidence: 70%

Dipeptidyl peptidase-4 inhibitor gemigliptin protects against vascular calcification in an experimental chronic kidney disease and vascular smooth muscle cells

Choi

Ryu

et al. 2017

PLoS ONE

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Although dipeptidyl peptidase-4 inhibitors, a class of antidiabetic drugs, have various pleiotropic effects, it remains undetermined whether gemigliptin has a beneficial effect on vascular calcification. Therefore, this study was performed to evaluate the effect of gemigliptin on vascular calcification in a rat model of adenine-induced chronic kidney disease and in cultured vascular smooth muscle cells. Gemigliptin attenuated calcification of abdominal aorta and expression of RUNX2 in adenine-induced chronic kidney disease rats. In cultured vascular smooth muscle cells, phosphate-induced increase in calcium content was reduced by gemigliptin. Gemigliptin reduced phosphate-induced PiT-1 mRNA expression, reactive oxygen species generation, and NADPH oxidase mRNA expression (p22phox and NOX4). The reduction of oxidative stress by gemigliptin was associated with the downregulation of phospho-PI3K/AKT expression. High phosphate increased the expression of frizzled-3 (FDZ3) and decreased the expression of dickkopf-related protein-1 (DKK-1) in the Wnt pathway. These changes were attenuated by gemigliptin treatment. Gemigliptin restored the decreased expression of vascular smooth muscle cells markers (α-SMA and SM22α) and increased expression of osteogenic makers (CBFA1, OSX, E11, and SOST) induced by phosphate. In conclusion, gemigliptin attenuated vascular calcification and osteogenic trans-differentiation in vascular smooth muscle cells via multiple steps including downregulation of PiT-1 expression and suppression of reactive oxygen species generation, phospho-PI3K/AKT, and the Wnt signaling pathway.

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“…It has been reported that vascular calcification is strongly correlated with chronic renal failure . Manivannan et al established an animal model of vascular calcification in CRF by feeding the animals with a diet containing 0.75% adenine . In the present study, we established chronic renal failure in rats by gavage with adenine.…”

Section: Discussionmentioning

confidence: 68%

Citrate attenuates vascular calcification in chronic renal failure rats

Liu

et al. 2017

APMIS

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Vascular calcification (VC) is a major contributor of cardiovascular dysfunction in chronic renal failure (CRF). Citrate binds calcium and inhibits the growth of calcium crystals. This present study intends to evaluate the effect of citrate on VC in adenine-induced CRF rats. The rats were randomly divided into five groups: the control group, the citrate control group, model group, model rats with low-dose treatment of citrate (216 mg/kg) and model rats with high-dose treatment of citrate (746 mg/kg). The rats were euthanized at 5 weeks with their blood and aorta in detection. The results showed that serum level of blood urea nitrogen, serum creatinine, phosphorus, calcium, and related renal failure function marker were elevated in the model group. Furthermore, the aortic calcium accumulation and alkaline phosphatase activity were significantly increased in the model group compared with control groups. Additionally, hematoxylin-eosin staining results demonstrated that the vascular calcification in aorta is significantly increased in the model group. Finally, the expression of VC-related proteins including bone morphogenetic protein and osteocalcin were increased in the model group, whereas alpha-smooth muscle actin was decreased in the model group compared with the control group. However, treatment with citrate caused a reversal effect of all the above events in a dose-dependent manner. In conclusion, citrate may attenuate vascular calcification in adenine-induced CRF rats.

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Diosgenin attenuates vascular calcification in chronic renal failure rats

Cited by 38 publications

References 40 publications

The In Vivo Effects of Adenine-Induced Chronic Kidney Disease on Some Renal and Hepatic Function and CYP450 Metabolizing Enzymes

The In Vivo Effects of Adenine-Induced Chronic Kidney Disease on Some Renal and Hepatic Function and CYP450 Metabolizing Enzymes

Dipeptidyl peptidase-4 inhibitor gemigliptin protects against vascular calcification in an experimental chronic kidney disease and vascular smooth muscle cells

Citrate attenuates vascular calcification in chronic renal failure rats

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