Heme oxygenase-1, a novel target for the treatment of diabetic complications: focus on diabetic peripheral neuropathy

Negi, Geeta; Nakkina, Vanaja; Kamble, Pallavi; Sharma, Shyam Sunder

doi:10.1016/j.phrs.2015.09.014

Cited by 44 publications

(31 citation statements)

References 118 publications

(48 reference statements)

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“…[48]. HO-1 has also been found to have potential neurovascular protective properties in diabetic neuropathy [49]. In our study, in the presence of high glucose, DPN mice showed a decrease in the level of Nrf2, which in turn led to decreases in the levels of HO-1 and NQO1.…”

Section: Discussionsupporting

confidence: 55%

Neuroprotective effect of diosgenin in a mouse model of diabetic peripheral neuropathy involves the Nrf2/HO-1 pathway

Jin-hong

Tian

et al. 2020

BMC Complement Med Ther

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Background: Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes. Diosgenin is a natural steroidal saponin with a variety of beneficial effects, including antidiabetic effects, and is a raw material for the synthesis of carrier hormones. In our study, we aimed to assess the antioxidant effects of diosgenin in diabetic mice. Methods: Male C57 mice were fed a high-fat diet for 8 weeks and intraperitoneally injected with streptozotocin (STZ) at a dose of 100 mg/kg for 2 consecutive days. Eligible mice were divided into the normal control group (CON), diabetic group (DM), low-dose diosgenin (50 mg/kg) group (DIO50) and high-dose diosgenin (100 mg/kg) group (DIO100). Treatment was started 6 weeks after the induction of diabetes by STZ and continued for 8 weeks. Blood sugar and body weight were monitored dynamically. The behavioural effects of diosgenin were detected by a hot tail immersion test and paw tactile responses. HE staining was used to evaluate edema and degeneration of the sciatic nerve. The levels of SOD, MDA and GPx were tested according to the instructions of the respective kits. The levels of Nrf2, HO-1 and NQO1 were detected by immunofluorescence and Western blotting. Statistical analysis was performed using SPSS, and P < 0.05 was considered statistically significant. Results: Diosgenin decreased the blood glucose levels and increased the body weight of diabetic mice. There was a significant increase in the tail withdrawal latency of diabetic animals, and mechanical hyperalgesia was significantly alleviated after diosgenin treatment. Histopathological micrographs of HE-stained sciatic nerves showed improvement after diosgenin treatment. Diosgenin attenuated the level of MDA but increased the activities of SOD and GPx. Diosgenin increased the expression of Nrf2, HO-1 and NQO1. Conclusions: Our results demonstrate that diosgenin can ameliorate behavioural and morphological changes in DPN by reducing oxidative stress. The Nrf2/HO-1 signalling pathway was involved in its neuroprotective effects.

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Section: Discussionsupporting

confidence: 55%

Neuroprotective effect of diosgenin in a mouse model of diabetic peripheral neuropathy involves the Nrf2/HO-1 pathway

Jin-hong

Tian

et al. 2020

BMC Complement Med Ther

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“…Exercise training increased HO‐1, which is an inducible HSP mainly involved in the protection against the adverse effects of oxidative stress . Previously, exercise training has been shown favorable effects on kidney oxidative stress in diabetes, but the HO‐1 responses have been very little studied.…”

Section: Discussionmentioning

confidence: 99%

“…38 Exercise training increased HO-1, which is an inducible HSP mainly involved in the protection against the adverse effects of oxidative stress. 39 Previously, exercise training has been shown favorable effects on kidney oxidative stress in diabetes, 29,40 but the HO-1 responses have been very little studied. Adaptations of endogenous antioxidants to oxidative stress and the beneficial effects of exercise on the markers of oxidative stress are well demonstrated.…”

Section: Discussionmentioning

confidence: 99%

Suppressed heat shock protein response in the kidney of exercise‐trained diabetic rats

Lappalainen

Oksala

Laaksonen

et al. 2018

Scandinavian Med Sci Sports

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Impaired expression of heat shock proteins (HSPs) and increased oxidative stress may contribute to the pathophysiology of diabetes by disrupted tissue protection. Acute exercise induces oxidative stress, whereas exercise training up-regulates endogenous antioxidant defenses and HSP expression. Although diabetic nephropathy is a major contributor to diabetic morbidity, information regarding the effect of HSPs on kidney protection is limited. This study evaluated the effects of eight-week exercise training on kidney HSP expression and markers of oxidative stress at rest and after acute exercise in rats with or without streptozotocin-induced diabetes. Induction of diabetes increased DNA-binding activity of heat shock factor-1, but decreased the expression of HSP72, HSP60, and HSP90. The inflammatory markers IL-6 and TNF-alpha were increased in the kidney tissue of diabetic animals. Both exercise training and acute exercise increased HSP72 and HSP90 protein levels only in non-diabetic rats. On the other hand, exercise training appeared to reverse the diabetes-induced histological changes together with decreased expression of TGF-beta as a key inducer of glomerulosclerosis, and decreased levels of IL-6 and TNF-alpha. Notably, HSP72 and TGF-beta were negatively correlated. In conclusion, impaired HSP defense seems to contribute to kidney injury vulnerability in diabetes and exercise training does not up-regulate kidney HSP expression despite the improvements in histopathological and inflammatory markers.

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“…HO1 is an anti-inflammatory protein, and its overexpression has been shown to prevent various inflammatory complications including diabetes [31]. Specifically, HO1 has been shown to protect against HG-induced retinal endothelial cells damage and also prevent vascular inflammatory response in hyperglycemia [32–34].…”

Section: Discussionmentioning

confidence: 99%

Aldose Reductase Inhibitor Protects against Hyperglycemic Stress by Activating Nrf2-Dependent Antioxidant Proteins

Shukla

Pal

Sonowal

et al. 2017

Journal of Diabetes Research

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We have shown earlier that pretreatment of cultured cells with aldose reductase (AR) inhibitors prevents hyperglycemia-induced mitogenic and proinflammatory responses. However, the effects of AR inhibitors on Nrf2-mediated anti-inflammatory responses have not been elucidated yet. We have investigated how AR inhibitor fidarestat protects high glucose-(HG-) induced cell viability changes by increasing the expression of Nrf2 and its dependent phase II antioxidant enzymes. Fidarestat pretreatment prevents HG (25 mM)-induced Thp1 monocyte viability. Further, treatment of Thp1 monocytes with fidarestat caused a time-dependent increase in the expression as well as the DNA-binding activity of Nrf2. In addition, fidarestat augmented the HG-induced Nrf2 expression and activity and also upregulated the expression of Nrf2-dependent proteins such as hemeoxygenase-1 (HO1) and NQO1 in Thp1 cells. Similarly, treatment with AR inhibitor also induced the expression of Nrf2 and HO1 in STZ-induced diabetic mice heart and kidney tissues. Further, AR inhibition increased the HG-induced expression of antioxidant enzymes such as SOD and catalase and activation of AMPK-α1 in Thp1 cells. Our results thus suggest that pretreatment with AR inhibitor prepares the monocytes against hyperglycemic stress by overexpressing the Nrf2-dependent antioxidative proteins.

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Heme oxygenase-1, a novel target for the treatment of diabetic complications: focus on diabetic peripheral neuropathy

Cited by 44 publications

References 118 publications

Neuroprotective effect of diosgenin in a mouse model of diabetic peripheral neuropathy involves the Nrf2/HO-1 pathway

Neuroprotective effect of diosgenin in a mouse model of diabetic peripheral neuropathy involves the Nrf2/HO-1 pathway

Suppressed heat shock protein response in the kidney of exercise‐trained diabetic rats

Aldose Reductase Inhibitor Protects against Hyperglycemic Stress by Activating Nrf2-Dependent Antioxidant Proteins

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