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Curcumin ameliorates streptozotocin-induced liver damage through modulation of endoplasmic reticulum stress-mediated apoptosis in diabetic rats.

Afrin R, Arumugam S, Soetikno V, Thandavarayan RA, Pitchaimani V, Karuppagounder V, Sreedhar R, Harima M, Suzuki H, Miyashita S, Nomoto M, Suzuki K, Watanabe K - Free Radic. Res. (2015)

Bottom Line: Moreover, treatment with curcumin markedly decreased the sub-arm of the UPR signaling protein such as phospho-double-stranded RNA-dependent protein kinase-like ER kinase, CCAAT/enhancer-binding protein homologous protein, tumor necrosis factor receptor-associated factor 2, and inositol-requiring enzyme1α; and inhibited tumor necrosis factor α, interleukin 1β, phospho-p38 mitogen-activated protein kinase, and apoptosis signal-regulating kinase 1 in liver tissues of diabetic rats.Apoptotic and anti-apoptotic signaling proteins, such as cleaved caspase-3 and B-cell lymphoma 2, were significantly increased and decreased, respectively in diabetic rats; curcumin treatment prevented all of these alterations.In summary, our results indicate that curcumin has the potential to protect the diabetic liver by modulating hepatic ERS-mediated apoptosis, and provides a novel therapeutic strategy for the diabetic liver damage.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences , Niigata , Japan.

ABSTRACT
We investigated the effect of curcumin on liver injury in diabetic rats induced by streptozotocin (STZ) through modulation of endoplasmic reticulum stress (ERS) and unfolded protein response (UPR). Experimental diabetes was induced by a single intraperitoneal injection of STZ (55 mg/kg), and curcumin was given at 100 mg/kg by gavage for 56 days. We observed that curcumin improved the morphological and histopathological changes, significantly decreased hepatic ERS marker protein: glucose-regulated protein 78, and improved liver function in diabetic rats. Moreover, treatment with curcumin markedly decreased the sub-arm of the UPR signaling protein such as phospho-double-stranded RNA-dependent protein kinase-like ER kinase, CCAAT/enhancer-binding protein homologous protein, tumor necrosis factor receptor-associated factor 2, and inositol-requiring enzyme1α; and inhibited tumor necrosis factor α, interleukin 1β, phospho-p38 mitogen-activated protein kinase, and apoptosis signal-regulating kinase 1 in liver tissues of diabetic rats. Apoptotic and anti-apoptotic signaling proteins, such as cleaved caspase-3 and B-cell lymphoma 2, were significantly increased and decreased, respectively in diabetic rats; curcumin treatment prevented all of these alterations. In summary, our results indicate that curcumin has the potential to protect the diabetic liver by modulating hepatic ERS-mediated apoptosis, and provides a novel therapeutic strategy for the diabetic liver damage.

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Time-course changes in blood glucose. Blood glucose increased progressively in the untreated diabetic rats following induction of diabetes. Curcumin treatment significantly reduced blood glucose in the beginning of treatment and these were maintained throughout the study period until sacrifice. Values are means ± SEM. ∗∗p < 0.01, ∗∗∗p < 0.001 versus Normal, ###p < 0.001 versus Control.
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Figure 1: Time-course changes in blood glucose. Blood glucose increased progressively in the untreated diabetic rats following induction of diabetes. Curcumin treatment significantly reduced blood glucose in the beginning of treatment and these were maintained throughout the study period until sacrifice. Values are means ± SEM. ∗∗p < 0.01, ∗∗∗p < 0.001 versus Normal, ###p < 0.001 versus Control.

Mentions: For the confirmation of diabetic model and the effect of treatment, the blood glucose level was checked periodically, which is shown in Figure 1; before treatment, the blood glucose level was significantly higher in diabetic rats than that of normal group but during the treatment period of 6 weeks curcumin treatment significantly decreased this blood glucose level. Moreover, it is also reported that curcumin has the capability to improve the pancreatic islets [34] and has been demonstrated in prevention of isolated β-cells death and dysfunction induced by STZ [34,35].


Curcumin ameliorates streptozotocin-induced liver damage through modulation of endoplasmic reticulum stress-mediated apoptosis in diabetic rats.

Afrin R, Arumugam S, Soetikno V, Thandavarayan RA, Pitchaimani V, Karuppagounder V, Sreedhar R, Harima M, Suzuki H, Miyashita S, Nomoto M, Suzuki K, Watanabe K - Free Radic. Res. (2015)

Time-course changes in blood glucose. Blood glucose increased progressively in the untreated diabetic rats following induction of diabetes. Curcumin treatment significantly reduced blood glucose in the beginning of treatment and these were maintained throughout the study period until sacrifice. Values are means ± SEM. ∗∗p < 0.01, ∗∗∗p < 0.001 versus Normal, ###p < 0.001 versus Control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4389763&req=5

Figure 1: Time-course changes in blood glucose. Blood glucose increased progressively in the untreated diabetic rats following induction of diabetes. Curcumin treatment significantly reduced blood glucose in the beginning of treatment and these were maintained throughout the study period until sacrifice. Values are means ± SEM. ∗∗p < 0.01, ∗∗∗p < 0.001 versus Normal, ###p < 0.001 versus Control.
Mentions: For the confirmation of diabetic model and the effect of treatment, the blood glucose level was checked periodically, which is shown in Figure 1; before treatment, the blood glucose level was significantly higher in diabetic rats than that of normal group but during the treatment period of 6 weeks curcumin treatment significantly decreased this blood glucose level. Moreover, it is also reported that curcumin has the capability to improve the pancreatic islets [34] and has been demonstrated in prevention of isolated β-cells death and dysfunction induced by STZ [34,35].

Bottom Line: Moreover, treatment with curcumin markedly decreased the sub-arm of the UPR signaling protein such as phospho-double-stranded RNA-dependent protein kinase-like ER kinase, CCAAT/enhancer-binding protein homologous protein, tumor necrosis factor receptor-associated factor 2, and inositol-requiring enzyme1α; and inhibited tumor necrosis factor α, interleukin 1β, phospho-p38 mitogen-activated protein kinase, and apoptosis signal-regulating kinase 1 in liver tissues of diabetic rats.Apoptotic and anti-apoptotic signaling proteins, such as cleaved caspase-3 and B-cell lymphoma 2, were significantly increased and decreased, respectively in diabetic rats; curcumin treatment prevented all of these alterations.In summary, our results indicate that curcumin has the potential to protect the diabetic liver by modulating hepatic ERS-mediated apoptosis, and provides a novel therapeutic strategy for the diabetic liver damage.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences , Niigata , Japan.

ABSTRACT
We investigated the effect of curcumin on liver injury in diabetic rats induced by streptozotocin (STZ) through modulation of endoplasmic reticulum stress (ERS) and unfolded protein response (UPR). Experimental diabetes was induced by a single intraperitoneal injection of STZ (55 mg/kg), and curcumin was given at 100 mg/kg by gavage for 56 days. We observed that curcumin improved the morphological and histopathological changes, significantly decreased hepatic ERS marker protein: glucose-regulated protein 78, and improved liver function in diabetic rats. Moreover, treatment with curcumin markedly decreased the sub-arm of the UPR signaling protein such as phospho-double-stranded RNA-dependent protein kinase-like ER kinase, CCAAT/enhancer-binding protein homologous protein, tumor necrosis factor receptor-associated factor 2, and inositol-requiring enzyme1α; and inhibited tumor necrosis factor α, interleukin 1β, phospho-p38 mitogen-activated protein kinase, and apoptosis signal-regulating kinase 1 in liver tissues of diabetic rats. Apoptotic and anti-apoptotic signaling proteins, such as cleaved caspase-3 and B-cell lymphoma 2, were significantly increased and decreased, respectively in diabetic rats; curcumin treatment prevented all of these alterations. In summary, our results indicate that curcumin has the potential to protect the diabetic liver by modulating hepatic ERS-mediated apoptosis, and provides a novel therapeutic strategy for the diabetic liver damage.

Show MeSH
Related in: MedlinePlus