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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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Related in: MedlinePlus

Hepatic expressions of CHOP, TRAF2, ASK1, and p-p38MAPK. Representative Western blots (lower panel) show specific bands for CHOP/GADD153 (A), TRAF2 (B), ASK1 (C), and p-p38MAPK (D); representative histograms (upper panel) show the band densities with relative β-tubulin. The blots are representatives of five independent experiments. Each bar represents mean ± SE. Normal, age-matched normal rats; Control, untreated diabetic rats; Curcumin, diabetic rats treated with curcumin 100 mg/kg/day. ∗∗p < 0.01, ∗∗∗p < 0.001 versus Normal, ##p < 0.01, ###p < 0.001 versus Control.
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Figure 4: Hepatic expressions of CHOP, TRAF2, ASK1, and p-p38MAPK. Representative Western blots (lower panel) show specific bands for CHOP/GADD153 (A), TRAF2 (B), ASK1 (C), and p-p38MAPK (D); representative histograms (upper panel) show the band densities with relative β-tubulin. The blots are representatives of five independent experiments. Each bar represents mean ± SE. Normal, age-matched normal rats; Control, untreated diabetic rats; Curcumin, diabetic rats treated with curcumin 100 mg/kg/day. ∗∗p < 0.01, ∗∗∗p < 0.001 versus Normal, ##p < 0.01, ###p < 0.001 versus Control.

Mentions: It has been proposed that enhancement of the hepatocyte protein expression of CHOP/GADD153 gene could eventually induce apoptosis. Immunoblot analysis revealed that the diabetic rats have demonstrated significant elevation of CHOP/GADD153 protein expression compared with the normal rats (Figure 4A) and curcumin treatment significantly decreased the increased liver CHOP expression.


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)

Hepatic expressions of CHOP, TRAF2, ASK1, and p-p38MAPK. Representative Western blots (lower panel) show specific bands for CHOP/GADD153 (A), TRAF2 (B), ASK1 (C), and p-p38MAPK (D); representative histograms (upper panel) show the band densities with relative β-tubulin. The blots are representatives of five independent experiments. Each bar represents mean ± SE. Normal, age-matched normal rats; Control, untreated diabetic rats; Curcumin, diabetic rats treated with curcumin 100 mg/kg/day. ∗∗p < 0.01, ∗∗∗p < 0.001 versus Normal, ##p < 0.01, ###p < 0.001 versus Control.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Hepatic expressions of CHOP, TRAF2, ASK1, and p-p38MAPK. Representative Western blots (lower panel) show specific bands for CHOP/GADD153 (A), TRAF2 (B), ASK1 (C), and p-p38MAPK (D); representative histograms (upper panel) show the band densities with relative β-tubulin. The blots are representatives of five independent experiments. Each bar represents mean ± SE. Normal, age-matched normal rats; Control, untreated diabetic rats; Curcumin, diabetic rats treated with curcumin 100 mg/kg/day. ∗∗p < 0.01, ∗∗∗p < 0.001 versus Normal, ##p < 0.01, ###p < 0.001 versus Control.
Mentions: It has been proposed that enhancement of the hepatocyte protein expression of CHOP/GADD153 gene could eventually induce apoptosis. Immunoblot analysis revealed that the diabetic rats have demonstrated significant elevation of CHOP/GADD153 protein expression compared with the normal rats (Figure 4A) and curcumin treatment significantly decreased the increased liver CHOP expression.

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