Klotho ameliorates the onset and progression of cataract via suppressing oxidative stress and inflammation in the lens in streptozotocin-induced diabetic rats

Ma, Zhongxu; Liu, Jingjing; Li, Jing; Jiang, Hao; Kong, Jun

doi:10.1016/j.intimp.2020.106582

Cited by 21 publications

(12 citation statements)

References 37 publications

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“…The reason for this difference may be that the concentration of H 2 O 2 they use (1 mM) is much higher than the concentration we use (300 μM), which leaded to serious oxidative damage to cells. However, Klotho alone has no effect on the expressions of the above proteins, which is similar to previous studies [ 28 ], implying that oxidative stress is essential for subsequent Nrf2 nuclear translocation and expression of HO-1 protein. The PI3K inhibitor (LY294002) and Nrf2 knockdown inhibited Nrf2 nuclear translocation and abolished the cytoprotection of Klotho.…”

Section: Discussionsupporting

confidence: 90%

“…This slightly differs from previous reports of Ma et al . [ 28 , 49 ] Although both studies have revealed that Klotho can promote nuclear translocation of Nrf2, previous reports have found that Klotho has no effect on the expression of cytoplasmic Nrf2. Some possible reasons for this difference include 1) different cell types (lens cells, cardiomyocytes and retinal pigment epithelial cells used in our study), 2) unique cell culture conditions and unique expression of signal molecules, and 3) different sources of Klotho.…”

Section: Discussionmentioning

confidence: 99%

“…It is reported that Klotho can markedly elevate SOD and GSH-PX activities as well as reduce MDA and lipid peroxidation levels in Human Umbilical Vein Endothelial Cells (HUVECs) [ 26 ], and increase the activities of superoxide SOD2 and CAT in mouse tubular epithelial cells (TCMK-1) induced by H 2 O 2 [ 27 ]. Klotho regulates the differentiation and apoptosis of eye lens epithelial cells [ 28 ]. Also, researchers have demonstrated marked differences in levels of Klotho mRNA and corresponding proteins between patients with clear lens and those with age-related cataract [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

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Recombinant human klotho protects against hydrogen peroxide-mediated injury in human retinal pigment epithelial cells via the PI3K/Akt-Nrf2/HO-1 signaling pathway

Wen

Zhang

et al. 2022

Bioengineered

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Globally, age-related macular degeneration (AMD) is a common irreversible ophthalmopathy. Oxidative stress of retinal pigment epithelial cells is involved in AMD occurrence and development. Klotho is an anti-aging protein with antioxidant properties. We investigated the protective properties of Klotho on hydrogen peroxide (H 2 O 2 )-induced injury of retinal pigment epithelial cells (ARPE-19 cells) and its associated pathomechanisms. We found that Klotho pretreatment for 24 h could up-regulate Bcl-2 levels, decrease the cleaved-caspase-3 and Bax levels, inhibit H 2 O 2 -induced ARPE-19 cell apoptosis, and promote cell proliferation. Klotho pretreatment inhibited the H 2 O 2 -mediated elevations of reactive oxygen species (ROS) in ARPE-19 cells. It enhanced antioxidant activities of the cells and restored the glutathione peroxidase (GPX), superoxide dismutase (SOD2), catalase (CAT), as well as malondialdehyde (MDA) levels to close to the normal level. N-acetylcysteine (NAC), a reactive oxygen scavenger, could reverse the harmful effects of H 2 O 2 on proliferation, apoptosis, and oxidative stress of ARPE-19 cells. Further, Klotho pretreatment enhanced Akt phosphorylation and expression as well as nuclear translocation of Nrf2 in H 2 O 2 -treated ARPE-19 cells. This indicates that Klotho protects cells from oxidative stress by activating phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)-nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) signaling pathway. Klotho is, therefore, a potential preventive or treatment option for AMD.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Recombinant human klotho protects against hydrogen peroxide-mediated injury in human retinal pigment epithelial cells via the PI3K/Akt-Nrf2/HO-1 signaling pathway

Wen

Zhang

et al. 2022

Bioengineered

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“…In addition, Garner B et al reported a correlation between hydroxyl radical formation in the lens and cataract severity [ 48 ]. There is also evidence that antioxidant compounds could prevent the lens from opacification and cataract formation [ 49 , 50 ]. An interesting findings in our study showed that there is no significant correlation between TAC/ascorbic acid and age ( Figure S3 ).…”

Section: Discussionmentioning

confidence: 99%

An Assessment of Cataract Severity Based on Antioxidant Status and Ascorbic Acid Levels in Aqueous Humor

Tsao

Chen

et al. 2022

Antioxidants

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Cataract is the leading cause of blindness throughout the world. Currently, the cataract severity evaluation is based on the subjective LOCS III guideline. To ameliorate the evaluation system and develop an objective and quantitative analysis, we investigated the relationships among aqueous humor total antioxidant capacity (AqTAC), ascorbic acid (AqAA) concentration, and cataract severity. In this study, we enrolled 130 cataract patients who underwent phacoemulsification between April 2019 and March 2020. The AqTAC and AqAA were measured by our own developed TAC assay and commercially available kit. Cataract severity was recorded by nuclear opalescence (NO) and cortical cataract (CC) degree according to LOCS III. Cumulative dissipated energy (CDE) during phacoemulsification was recorded to verify the severity of the cataract. As a result, we found a moderate correlation between AqTAC and CDE (p < 0.001). In addition, we found AqTAC independently associated with the CDE when analyzed by multivariate linear regression (p < 0.001). AqTAC also negatively correlated to cataract severity when measured by NO and CC (p = 0.012 in NO grade 3 vs. grade 1; p = 0.012 in CC grade 2 vs. grade 1; p < 0.001 in CC grade 3 vs. grade 1). We further found AqAA provided 71.9 ± 13.5% of AqTAC, and showed a high correlation (rho = 0.79, p < 0.001). In conclusion, we found a significant correlation between AqTAC/AqAA and cataract severity measured by CDE. The correlation was superior to the correlation between LOCS III and CDE. Aqueous humor TAC owns the potential to assess cataracts in an objective and quantitative way.

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“…As a result, rutaecarpine shows little activity against the active polyol pathway under our test settings. Hyperglycemia can produce reactive oxygen species through a variety of processes, including raised an increase in advanced glycation end-products as well as activation of the polyol pathway, overproduction of mitochondrial superoxide and altered activity of protein kinase C activity 36,37 . Rutaecarpine can quench ROS while also increasing the expression of the antioxidant enzymes 38 .…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Rutaecarpine in Streptozotocin-Induced Diabetes Cataracts Through the Inhibition of Aldose Reductase Activity in Male Albino Rats

Chen¹,

Zhang²,

Liu³

et al. 2023

International J. of Pharmacology

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Background and Objective: Diabetes mellitus (DM) is a major metabolic disease which affect the millions of people worldwide. The DM induces the several associate diseases like cataract, renal and hepatic failure. The main enzyme aldose reductase during the polyol pathway serves an important part in the formation of cataracts in diabetic conditions. Rutaecarpine (RT), which is an indolopyridoquinazoline alkaloid and principal compound of evodia shows therapeutic activity against several chronic illnesses. It is proven to be effective in the treatment of diabetes mellitus via altering oxidative stress and inflammation. The goal of current research was to scrutinize the pharmacological action of rutaecarpine in streptozotocin-induced diabetic cataracts in rodents. Materials and Methods: All the animals were divided into five groups and streptozotocin-induced diabetic rats were supplemented with different doses of rutaecarpine. The formation of cataracts was evaluated using the scoring technique by observer and lens digital picture. Other biochemical parameters were also assessed such as blood, insulin, blood glucose, body weight, sorbitol content, protein carbonyl content, mRNA and expression of aldose reductase in each group of rats. We also measured the kinetics properties of aldose reductase. Results: Administration of rutaecarpine alters all biochemical parameters compared to diabetic cataract rats. Rutaecarpine significantly stuck the formation of cataracts in the rats in a dose-dependent manner. The kinetic properties of aldose reductase i.e., V max , K m and K i had also attenuated in diabetic cataract rats as well as mRNA and protein expression. Conclusion: Collectively, we can say that rutaecarpine has the potential to reduce the progression of cataracts in a diabetic case via the reduction of aldose reductase.

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Klotho ameliorates the onset and progression of cataract via suppressing oxidative stress and inflammation in the lens in streptozotocin-induced diabetic rats

Cited by 21 publications

References 37 publications

Recombinant human klotho protects against hydrogen peroxide-mediated injury in human retinal pigment epithelial cells via the PI3K/Akt-Nrf2/HO-1 signaling pathway

Recombinant human klotho protects against hydrogen peroxide-mediated injury in human retinal pigment epithelial cells via the PI3K/Akt-Nrf2/HO-1 signaling pathway

An Assessment of Cataract Severity Based on Antioxidant Status and Ascorbic Acid Levels in Aqueous Humor

Protective Effect of Rutaecarpine in Streptozotocin-Induced Diabetes Cataracts Through the Inhibition of Aldose Reductase Activity in Male Albino Rats

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