Ramipril and resveratrol co‐treatment attenuates RhoA/ROCK pathway‐regulated early‐stage diabetic nephropathy‐associated glomerulosclerosis in streptozotocin‐induced diabetic rats

Xiang, Peng; Su, Haiyan; Liang, Dali; Li, Jeihua; Ting, Wei-Jen; Liao, Shih-Chieh; Huang, Chih‐Yang

doi:10.1002/tox.22758

Cited by 12 publications

(9 citation statements)

References 31 publications

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“…Generally, nephropathy is a common cause of mortality in patients with DM (Skupien et al, 2019). This syndrome is characterized by the progressive loss of renal functions and persistent albuminuria (Lim, 2014) followed by certain pathological changes such as glomerular mesangial expansion and accumulation of extracellular matrix as indicators of the incidence of glomerulosclerosis (Peng et al, 2019). Moreover, high levels of glucose can impair the growth of cells overtime and the production of growth factors as well as the occurrence of genes that eventually increase the extracellular matrix (Vallon & Komers, 2011).…”

Section: Introductionmentioning

confidence: 99%

LCZ696 mitigates diabetic-induced nephropathy through inhibiting oxidative stress, NF-κB mediated inflammation and glomerulosclerosis in rats

Mohany

Alanazi

Alqahtani

et al. 2020

PeerJ

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Background Diabetic nephropathy (DN) is among the most common microvascular complications of diabetes resulting in end-stage renal disease and therefore search for candidates which can ameliorate the kidney function is needed simultaneously with standard diabetic pharmacotherapy. The current study was aimed to investigate the effect of long term sacubitril/valsartan therapy (LCZ696) in diabetic rats to assess its ameliorative impact against various pathological parameters such as oxidative stress, inflammation and glomerulosclerosis associated with chronic DN. Methods A single dose (60 mg/kg/day) of STZ was used to induce type 1 diabetes in adult male wistar rats. 2 weeks after diabetes induction, these rats were treated orally with valsartan (31 mg/kg) or LCZ696 (68 mg/kg) for 6 weeks. At end of the treatment period, serum and kidney samples were collected and analyzed. The serum levels of glucose, insulin, urea, creatinine, TNF-α, IL-1β, IL-6 and IL-10 levels were estimated. In renal tissue homogenate, the levels of inflammatory markers such as TNF-α, IL-1β, IL-6, NF-kB along with oxidative stress biomarkers including thiobarbituric acid-reacting substances (TBARs), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST) were assessed. Histological changes were observed in kidney. Results Time course therapy withLCZ696 and valsartan in diabetic rats resulted in significant reduction of serum glucose, urea and creatinine levels (P < 0.05). Additionally, serum of treated diabetic rats showed a diminution in inflammatory (TNF-α, IL-1β, IL-6) and increment in anti-inflammatory (IL-10) cytokines levels (P < 0.05). Tissue homogenate of the kidney extracted from LCZ696 and valsartan treated diabetic rats revealed a substantial reduction in the levels of inflammatory markers such as TNF-α, IL-1β, IL-6, NF-kB and sufficient restoration of anti-oxidant enzyme levels (P < 0.05). Finally, in the histological sections of the kidney, prevention of renal injury was observed with limited necrosis and inflammatory cells infiltration. Conclusion Present data suggest that LCZ696 has sufficient therapeutic potential to restrict DN progression through inhibiting inflammation, oxidative stress and glomerulosclerosis.

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Section: Introductionmentioning

confidence: 99%

LCZ696 mitigates diabetic-induced nephropathy through inhibiting oxidative stress, NF-κB mediated inflammation and glomerulosclerosis in rats

Mohany

Alanazi

Alqahtani

et al. 2020

PeerJ

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“…So we deduced that silencing of ANGPTL8 ameliorated IR by suppressing JNK signaling in trophoblast cells. ROCK signaling was also activated in diabetic rats ( 26 ), and a ROCK inhibitor, fasudil, has been demonstrated to retrained experimental IR in trophoblast cells in our another paper ( 28 ).…”

Section: Discussionmentioning

confidence: 91%

“…JNK signaling has been reported to be activated in STZ-induced diabetic rats ( 26 ), and JNK inhibitor alleviated 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced IR in adipocytes ( 27 ). In our study, JNK agonist aggravated IR induced by high concentration of insulin treatment, and JNK antagonist attenuated IR in trophoblast cells.…”

Section: Discussionmentioning

confidence: 99%

Silencing of ANGPTL8 Alleviates Insulin Resistance in Trophoblast Cells

Bai

Zhang

et al. 2021

Front. Endocrinol.

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This study aims to investigate the effect of angiopoietin like 8 (ANGPTL8) on gestational diabetes mellitus (GDM) and insulin resistance (IR). The GDM model was induced by high fat diet in mice, and IR was observed. The expression and secretion of ANGPTL8 were promoted in placenta of GDM mice. IR was induced in trophoblast cell HTR-8/SVneo by treatment of high concentration of insulin, and the expression levels of ANGPTL8 were increased. Silencing of ANGPTL8 alleviated IR and decreased glucose uptake in HTR-8/SVneo cells. However, the inflammation and oxidative stress in IR cells were not restrained by ANGPTL8 knockdown. In addition, c-Jun N-terminal kinase (JNK) signaling was activated by IR, which was inhibited by silencing of ANGPTL8. The effect of ANGPTL8 knockdown on IR was attenuated by JNK antagonist, and aggravated by JNK agonist, suggesting that ANGPTL8 affected IR by regulating JNK signaling. In conclusion, we demonstrated that the silencing of ANGPTL8 ameliorated IR by inhibiting JNK signaling in trophoblast cells. These findings may provide novel insights for diagnosis and treatment of GDM in clinic.

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“…The results revealed that resveratrol is a potential adjunct to ARBs for decreasing urinary albumin excretion in diabetic nephropathy patients. Another investigation by Peng et al showed that ramipril (10 mg/kg) and resveratrol (15 mg/kg) co‐treatment have synergistic therapeutic effects and reverses glomerulosclerosis in rats with early‐stage diabetic nephropathy 41 …”

Section: Diabetic Nephropathy Pathogenesis: Nutraceuticals Can Improvmentioning

confidence: 99%

Therapeutic application of nutraceuticals in diabetic nephropathy: Current evidence and future implications

Dehdashtian

Pourhanifeh

Karim

et al. 2020

Diabetes Metabolism Res

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Summary Diabetes mellitus (DM) is a common metabolic disease which may cause several complications, such as diabetic nephropathy (DN). The routine medical treatments used for DM are not effective enough and have many undesirable side effects. Moreover, the global increased prevalence of DM makes researchers try to explore potential complementary or alternative treatments. Nutraceuticals, as natural products with pharmaceutical agents, have a wide range of therapeutic properties in various pathologic conditions such as DN. However, the exact underlying mechanisms have not been fully understood. The purpose of this review is to summarize recent findings on the effect of nutraceuticals on DN.

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Ramipril and resveratrol co‐treatment attenuates RhoA/ROCK pathway‐regulated early‐stage diabetic nephropathy‐associated glomerulosclerosis in streptozotocin‐induced diabetic rats

Cited by 12 publications

References 31 publications

LCZ696 mitigates diabetic-induced nephropathy through inhibiting oxidative stress, NF-κB mediated inflammation and glomerulosclerosis in rats

LCZ696 mitigates diabetic-induced nephropathy through inhibiting oxidative stress, NF-κB mediated inflammation and glomerulosclerosis in rats

Silencing of ANGPTL8 Alleviates Insulin Resistance in Trophoblast Cells

Therapeutic application of nutraceuticals in diabetic nephropathy: Current evidence and future implications

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