Peer Review #1 of "Allantoin ameliorates chemically-induced pancreatic β-cell damage through activation of the imidazoline I3 receptors (v0.2)" [peer_review]

2015 unpublished
Objective: Allantoin is the primary active compound in yams (Dioscorea spp.). Recently, allantoin has been demonstrated to activate imidazoline 3 (I3) receptors located in pancreatic tissues. Thus, the present study aimed to investigate the role of allantoin in the effect to improve damage induced in pancreatic β-cells by streptozotocin (STZ) via the I3 receptors. Research Design and Methods: The effect of allantoin on STZ-induced apoptosis in pancreatic β-cells was examined using the
more » ... triplex assay, live/dead cell double staining assay, flow cytometric analysis, and Western blottings. The potential mechanism was investigated using KU14R: an I3 receptor antagonist, and U73122: a phospholipase C (PLC) inhibitor. The effects of allantoin on serum glucose and insulin secretion were measured in STZ-treated rats. Results: Allantoin attenuated apoptosis and cytotoxicity and increased the viability of STZ-induced β-cells in a dose-dependent manner; this effect was suppressed by KU14R and U73112. Allantoin decreased the level of caspase-3 and increased the level of phosphorylated B-cell lymphoma 2 (Bcl-2) expression detected by Western blotting. The improvement in β-cells viability was confirmed using flow cytometry analysis. Daily injection of allantoin for 8 days in STZtreated rats significantly lowered plasma glucose and increased plasma insulin levels. This action was inhibited by treatment with KU14R. Conclusion: Allantoin ameliorates the damage of β-cells induced by STZ. The blockade by pharmacological inhibitors indicated that allantoin can activate the I3 receptors through a PLC-related pathway to decrease this damage. Therefore, allantoin and related analogs may be effective in the therapy for β-cell damage. Abstract 20 Objective: Allantoin is the primary active compound in yams (Dioscorea spp.). Recently, allantoin 21 has been demonstrated to activate imidazoline 3 (I3) receptors located in pancreatic tissues. Thus, 22 the present study aimed to investigate the role of allantoin in the effect to improve damage induced 23 in pancreatic β-cells by streptozotocin (STZ) via the I3 receptors. 24 Research Design and Methods: The effect of allantoin on STZ-induced apoptosis in pancreatic β-25 cells was examined using the ApoTox-Glo triplex assay, live/dead cell double staining assay, flow 26 cytometric analysis, and Western blottings. The potential mechanism was investigated using 27 KU14R: an I3 receptor antagonist, and U73122: a phospholipase C (PLC) inhibitor. The effects of 28 allantoin on serum glucose and insulin secretion were measured in STZ-treated rats. 29 Results: Allantoin attenuated apoptosis and cytotoxicity and increased the viability of STZ-30 induced β-cells in a dose-dependent manner; this effect was suppressed by KU14R and U73112. 31 Allantoin decreased the level of caspase-3 and increased the level of phosphorylated B-cell 32 lymphoma 2 (Bcl-2) expression detected by Western blotting. The improvement in β-cells viability 33 was confirmed using flow cytometry analysis. Daily injection of allantoin for 8 days in STZ-treated 34 rats significantly lowered plasma glucose and increased plasma insulin levels. This action was 35 inhibited by treatment with KU14R. 36 Conclusion: Allantoin ameliorates the damage of β-cells induced by STZ. The blockade by 37 pharmacological inhibitors indicated that allantoin can activate the I3 receptors through a PLC-38 related pathway to decrease this damage. Therefore, allantoin and related analogs may be effective 39 in the therapy for β-cell damage. 40 41
doi:10.7287/peerj.1105v0.2/reviews/1 fatcat:vnpyg4lhvvgvhniqi5gqthe5wq