Ellagic acid protects against diabetic nephropathy in rats by regulating the transcription and activity of Nrf2

AlTamimi, Jozaa Z.; AlFaris, Nora A.; Alshammari, Ghedeir M.; Alagal, Reham I.; Aljabryn, Dalal H.; Aldera, Hussain; Alrfaei, Bahauddeen M.; Alkhateeb, Mahmoud; Yahya, Mohammed Abdo

doi:10.1016/j.jff.2021.104397

Cited by 27 publications

(36 citation statements)

References 80 publications

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“…27 Nevertheless, ROS overproduction and oxidative stress are widely accepted theory for explaining DN. 23 In the present study, we demonstrated that MDA level significantly increased, while the activity of GSH and CAT which are antioxidant defense enzymes significantly decreased in the kidney of STZ-induced diabetic rats. These findings of the present study suggest that SA and EA have a renoprotective effect against oxidative stress by down-regulating lipid peroxidation enzymes and up-regulating antioxidant defense enzymes.…”

Section: Discussionsupporting

confidence: 57%

Synergistic effects of sinapic acid and ellagic acid ameliorate streptozotocin-induced diabetic nephropathy by inhibiting apoptosis, DNA damage, and structural deterioration in rats

Altındağ

Özdek

2021

Hum Exp Toxicol

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Introduction Diabetic nephropathy (DN), a global problem that threatens human health, is an important reason for chronic kidney disease and kidney failure. In our study, it was aimed to investigate the individual and combined effects of SA and EA in streptozotocin (STZ)-induced rats. Methods The groups are as follows: Control, untreated diabetic, diabetic treated with Sinapic acid (SA), diabetic treated with Ellagic acid (EA), diabetic treated with SA and EA, treated with SA, treated with EA, and treated with SA and EA. Total kidney volume, total glomerulus volume, total filtration space volume, caspase-3, and 8-OHdG immunoreactivity, Malondialdehyde (MDA), Glutathione (GSH), Catalase (CAT), serum urea, and creatinine levels were evaluated by stereological, immunohistochemical, and biochemical methods. Results The findings of the study showed that total kidney volume, total glomerulus volume, total filtration gap volume, caspase-3, and 8-OHdG immunoreactivity, MDA, serum urea, and creatinine levels significantly increased in the untreated diabetic group compared to the control group. Also, severe mesangial and glomerular enlargement, extracellular matrix accumulation, and glomerular and tubular basal membrane thickness were observed in the tubulointerstitial and glomerular of the diabetic rats. However, individual and combined treatments of SA and EA ameliorated these histological changes. Additionally, decreased GSH and CAT in the untreated diabetic group increased by SA and EA treatment. Conclusions The findings suggest that treatment of SA and EA prevent apoptosis and DNA damage and structural changes in STZ-induced DN. However, the combined treatment of SA and EA were more effective than their individual treatments in all parameters except serum urea and creatinine.

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Section: Discussionsupporting

confidence: 57%

Synergistic effects of sinapic acid and ellagic acid ameliorate streptozotocin-induced diabetic nephropathy by inhibiting apoptosis, DNA damage, and structural deterioration in rats

Altındağ

Özdek

2021

Hum Exp Toxicol

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“…The expression of defense genes coding antioxidant proteins is mediated by Nrf2-Keap1 pathway, which is switched on or off directly by ROS so as to be a signaling pathway committed to the oxidant elimination [ 53 ]. An increasing number of studies demonstrate that in oxidative stress induced diseases (such as diabetes induced tissue damage, memory impairment, and hepatic injury, but not gut diseases-related evidences), EA elevates the activities SOD and glutathione (GSH) and declines the MDA levels by increasing the nuclear translocation of Nrf2, thereby protecting cells from the free radical damage [ 54 , 55 , 56 , 57 , 58 ]. In the present study, EA treatments did not change the gene expression of nqo1 in the small intestine, but up-regulated ho-1 , nrf2 and keap1 mRNA levels of ileal mucosa of piglets.…”

Section: Discussionmentioning

confidence: 99%

Ellagic Acid Alleviates Oxidative Stress by Mediating Nrf2 Signaling Pathways and Protects against Paraquat-Induced Intestinal Injury in Piglets

et al. 2022

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The gastrointestinal tract is a key source of superoxide so as to be one of the most vulnerable to oxidative stress damage. Ellagic acid (EA), a polyphenol displays widely biological activities owing to its strong antioxidant properties. Here, we investigated the protective benefits of EA on oxidative stress and intestinal barrier injury in paraquet (PQ)-challenged piglets. A total of 40 weaned piglets were randomly divided into five groups: Control, PQ, 0.005% EA-PQ, 0.01% EA-PQ, and 0.02% EA-PQ. Piglets were intraperitoneally injected with 4 mg/kg (BW) PQ or saline on d-18, and sacrificed on d-21 of experiment. EA treatments eliminated growth-check induced by PQ and increased serum superoxide dismutase (SOD) activity but decreased serum malondialdehyde (MDA) level as compared to PQ group. EA supplementation promoted Nrf2 nuclear translocation and enhanced heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO1) protein abundances of small intestinal mucosa. Additionally, EA improved PQ-induced crypt deepening, goblet cells loss, and villi morphological damage. Consistently, EA increased tight junction protein expression as was evident from the decreased serum diamine oxidase (DAO) levels. EA could ameliorate the PQ-induced oxidative stress and intestinal damage through mediating Nrf2 signaling pathway. Intake of EA-rich food might prevent oxidative stress-mediated gut diseases.

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“…This disruption allows Nrf2 translocation to the nucleus, in which Nrf2 binds antioxidant response elements (AREs) in the promoter region of several antioxidant genes, initiating their transcription [ 66 ]. Several studies have showed that uncontrolled diabetes significantly reduced Nrf2 expression levels in different tissues, where activation of the Nrf2 signaling pathway prevents the development of diabetes and diabetic complications [ 67 , 68 , 69 ]. In line with previous reports, the obtained results revealed that Nrf2 transcriptional level was downregulated in the hepatic tissues of rats in response to STZ-induced diabetes ( Figure 5 B).…”

Section: Discussionmentioning

confidence: 99%

Possible Synergistic Antidiabetic Effects of Quantified Artemisia judaica Extract and Glyburide in Streptozotocin-Induced Diabetic Rats via Restoration of PPAR-α mRNA Expression

Saeedan

Soliman

Abdel-Rahman

et al. 2021

Biology

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Several members of the genus Artemisia are used in both Western and African traditional medicine for the control of diabetes. A considerable number of diabetic patients switch to using oral antidiabetic drugs in combination with certain herbs instead of using oral antidiabetic drugs alone. This study examined the effect of Artemisia judaica extract (AJE) on the antidiabetic activity of glyburide (GLB) in streptozotocin (STZ)-induced diabetes. Forty-two male Wistar rats were divided into seven equal groups. Normal rats of the first group were treated with the vehicle. The diabetic rats in the second–fifth groups received vehicle, GLB (5 mg/kg), AJE low dose (250 mg/kg), and AJE high dose (500 mg/kg), respectively. Groups sixth–seventh were treated with combinations of GLB plus the lower dose of AJE and GLB plus the higher dose of AJE, respectively. All administrations were done orally for eight weeks. Fasting blood glucose (FBG) and insulin levels, glycated hemoglobin (HbA1c) percentage, serum lipid profile, and biomarkers of oxidative stress were estimated. The histopathological examination of the pancreas and the immunohistochemical analysis of anti-insulin, anti-glucagon, and anti-somatostatin protein expressions were also performed. The analysis of the hepatic mRNA expression of PPAR-α and Nrf2 genes were performed using quantitative RT-PCR. All treatments significantly lowered FBG levels when compared with the STZ-control group with the highest percentage reduction exhibited by the GLB plus AJE high dose combination. This combination highly improved insulin levels, HbA1c, and lipid profile in blood of diabetic rats compared to GLB monotherapy. In addition, all medicaments restored insulin content in the β-cells and diminished the levels of glucagon and somatostatin of the α- and δ-endocrine cells in the pancreatic islets. Furthermore, the GLB plus AJE high dose combination was the most successful in restoring PPAR-α and Nrf2 mRNA expression in the liver. In conclusion, these data indicate that the GLB plus AJE high dose combination gives greater glycemic improvement in male Wistar rats than GLB monotherapy.

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Ellagic acid protects against diabetic nephropathy in rats by regulating the transcription and activity of Nrf2

Cited by 27 publications

References 80 publications

Synergistic effects of sinapic acid and ellagic acid ameliorate streptozotocin-induced diabetic nephropathy by inhibiting apoptosis, DNA damage, and structural deterioration in rats

Synergistic effects of sinapic acid and ellagic acid ameliorate streptozotocin-induced diabetic nephropathy by inhibiting apoptosis, DNA damage, and structural deterioration in rats

Ellagic Acid Alleviates Oxidative Stress by Mediating Nrf2 Signaling Pathways and Protects against Paraquat-Induced Intestinal Injury in Piglets

Possible Synergistic Antidiabetic Effects of Quantified Artemisia judaica Extract and Glyburide in Streptozotocin-Induced Diabetic Rats via Restoration of PPAR-α mRNA Expression

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