Treatment with crocin suppresses diabetic nephropathy progression via modulating TGF-β1 and oxidative stress in an experimental model of pinealectomized diabetic rats

Keelo, Rihab Mudhafar Ali Hammood; Elbe, Hülya; Bicer, Yasemin; Yiğittürk, Gürkan; Koca, Oğuzhan; Karayakali, Melike; Acar, Derya; Altınöz, Eyüp

doi:10.1016/j.cbi.2021.109733

Cited by 14 publications

(7 citation statements)

References 45 publications

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“…A variety of drugs have been tried to inhibit the expression of superoxide dismutase (SOD) and malondialdehyde (MDA) to suppress oxidative stress. Among them, diphenyl diselenide (Wang et al 2021 ), crocin (Ali Hammood Keelo et al 2022 ), and other drugs have been proved by animal experiments to reduce oxidative stress and improve renal dysfunction. In addition, autophagy, disorder of glucose and lipid metabolism, and genetics mentioned above also play an important role in the pathogenesis of DN, and these mechanisms interact with each other constantly.…”

Section: Discussionmentioning

confidence: 99%

Tanshinone IIA is superior to paricalcitol in ameliorating tubulointerstitial fibrosis through regulation of VDR/Wnt/β-catenin pathway in rats with diabetic nephropathy

Zeng,

Wang,

Hong

et al. 2023

Naunyn-Schmiedeberg's Arch Pharmacol

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Glomerulosclerosis and tubulointerstitial fibrosis (TIF) are closely involved in the development of diabetic nephropathy (DN). Moreover, the development of TIF is closely related to epithelial-to-mesenchymal transition (EMT). Tanshinone IIA (Tan) has various pharmacological effects, especially the anti-fibrotic effect. And it is mainly used in the clinical treatment of cardiovascular diseases. Currently, the protective effect of Tan on DN and its possible mechanism have not been clearly elucidated. Our previous studies illustrated that Tan could improve the EMT of HK-2 cells induced by high glucose by regulating the vitamin D receptor (VDR)/Wnt/β-catenin pathway. Here, we collected demographic information and laboratory results from the National Health and Nutrition Examination Survey (NHANES) database in order to investigate the relationship between VD and DN. Then, we established a DN model and treated DN rats with Tan and paricalcitol (Par) for 6 weeks. We subsequently compared the changes in general condition, renal function, pathological changes, and TIF-related protein expression levels of control rats, DN rats induced by STZ, DN rats with Tan at 5.4 mg/kg, DN rats with Tan at 10.8 mg/kg, and DN rats with Par at 0.054 µg/kg, to explore the effect and mechanism of Tan and Par on DN rats. The results showed that VD had a protective effect against DN in diabetic patients. And we found that Tan had a protective effect on renal fibrosis in DN rats, which was superior to Par in improving the symptoms of “three more and one less,” reducing fasting blood glucose level, improving renal index, BUN/SCr, and UACR, reducing histopathological damage of kidney, and improving the expression of fibrosis-related proteins in kidney tissue by regulating VDR/Wnt/β-catenin pathway. Tan was superior to Par in ameliorating tubulointerstitial fibrosis by regulating VDR/Wnt/β-catenin pathway in rats with diabetic nephropathy.

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Section: Discussionmentioning

confidence: 99%

Tanshinone IIA is superior to paricalcitol in ameliorating tubulointerstitial fibrosis through regulation of VDR/Wnt/β-catenin pathway in rats with diabetic nephropathy

Zeng,

Wang,

Hong

et al. 2023

Naunyn-Schmiedeberg's Arch Pharmacol

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“…Crocin (Cr), an exclusive water‐soluble carotenoid that is considered as one of the key constituents of saffron, is well identified as a potent antioxidant. Various studies have verified the ability of crocin to induce several pharmacological effects, such as prevention of cardiovascular diseases, 11 inhibition of tumor cell proliferation, 12 renal protection, 13 neuroprotection 14 and hepatoprotection 15 . Crocin can protect cells from oxidative stress by scavenging free radicals, notably superoxide anions.…”

Section: Introductionmentioning

confidence: 99%

The protective effect of crocin against testicular toxicity induced by ionizing radiation via AKT/FOXO pathway

El‐Sheikh,

Aziz,

Abdelrahman

et al. 2023

Environmental Toxicology

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Crocin, a pharmacologically active component of Crocus sativus L. (saffron), has been informed to be beneficial in the treatment of stress‐related oxidative impairment. In the present study, we examined the protective role of crocin against testicular damage induced by radiation (acute and fractionated) and the alteration of the AKT/FOXO signaling pathway. Male Wister albino rats were exposed to acute dose of 6 Gy and a fractionated dose of gamma radiation (2 Gy every 2 days up to 6 Gy total doses). Rats were pretreated intraperitoneally with crocin in a dose of 50 mg/kg for seven consecutive days prior to exposure to irradiation at a level of 6 Gy and during the fractionated irradiation of rats. Control groups were run concurrently. Ionizing radiation caused changes in the level of oxidative stress biomarkers manifested as elevation of thiobarbituric acid reactive substance, total nitrate/nitrite and reactive oxygen species (ROS) associated with a decrease in catalase as well as in the level of inflammatory parameters (decrease in expression of Nrf2 which was related to a significant increase in expression of NF‐κB p65). Irradiation produced cellular damage characterized by an increase in serum lactate dehydrogenase. These findings were aligned with increased expression of the forkhead box O‐1 (FOXO‐1) and activation of protein kinase B (AKT) pathway. Irradiation of rats led to reduction in serum testosterone level and testicular weights. Pretreatment with the indicated dose of crocin shielded against the changes in all the evaluated parameters. Administration of crocin can be introduced as a novel preclinical approach for regulation of testicular damage induced by radiation; via controlling the ongoing oxidative stress and inflammatory reaction as well as activation FOXO/AKT signaling pathway.

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“…DM includes a syndrome that occurs as high blood sugar interferes with the metabolism of fats, carbohydrates, and proteins. As a result, it can increase the risk of vascular disease (3).…”

Section: Introductionmentioning

confidence: 99%

Effect of crocin and treadmill exercise on oxidative stress and heart damage in diabetic rats

Pourmousavi¹,

Asadi²,

Zehsaz³

et al. 2023

Preprint

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Objective: In diabetes the production of free radicals and inflammatory agents in the heart tissue is increased and the expression of genes associated with the induction of apoptosis is altered. Considering the importance of common cardiovascular disorders in diabetes, this study investigated the effect of eight weeks of aerobic exercise and kerosene use alone, as well as tissue damage and oxidative stress caused by diabetes in the heart of adult rats. Materials and Methods: To induce diabetes, streptozotocin 50 mg/kg was injected as a single dose intraperitoneally. After 72 hours, blood glucose levels were monitored by a glucometer, and blood glucose above 250 mg/dl was considered diabetes. Continuous treadmill exercise was performed for eight weeks by placing the animal on the treadmill. Next, the animals were anesthetized, and samples were taken from the hearts and frozen in liquid nitrogen. Then, superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) were measured in the cardiac tissue. Finally, the hearts of half of the animals were immediately immersed in formalin solution for histological changes. Results: According to our findings, diabetes increased lipid peroxidation, which was characterized by increased MDA levels in the control diabetes group and decreased SOD and GPx levels (P <0.05). It also changes the balance of expression of genes associated with apoptosis control, increased Bcl-2-associated X (Bax) expression, and decreased Bcl-2 expression (P <0.05). Also, we observed the induction of apoptosis in cardiac tissue. Using eight weeks of continuous exercise and administration of crocin significantly reduced blood sugar levels and lipid peroxidation and increased the activity of antioxidant enzymes and Bcl-2 gene expression compared to the diabetes control group. In addition, continuous exercise and kerosene improved the oxidative stress parameters in the control group. Conclusions: The results of this study showed that diabetes could cause oxidative stress and heart dysfunction. Moreover, simultaneously and separately, aerobic exercise with treadmill and crocin administration can reduce these disorders and prevent apoptosis in the heart tissue.

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Treatment with crocin suppresses diabetic nephropathy progression via modulating TGF-β1 and oxidative stress in an experimental model of pinealectomized diabetic rats

Cited by 14 publications

References 45 publications

Tanshinone IIA is superior to paricalcitol in ameliorating tubulointerstitial fibrosis through regulation of VDR/Wnt/β-catenin pathway in rats with diabetic nephropathy

Tanshinone IIA is superior to paricalcitol in ameliorating tubulointerstitial fibrosis through regulation of VDR/Wnt/β-catenin pathway in rats with diabetic nephropathy

The protective effect of crocin against testicular toxicity induced by ionizing radiation via AKT/FOXO pathway

Effect of crocin and treadmill exercise on oxidative stress and heart damage in diabetic rats

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