Antidiabetic and renoprotective effect of Anogeissus acuminata leaf extract on experimentally induced diabetic nephropathy

2018 ◽  
Vol 29 (4) ◽  
pp. 359-364 ◽  
Author(s):  
Archana M. Navale ◽  
Archana Paranjape

Abstract Background Diabetic nephropathy is the leading cause of end-stage renal disease. Hyperglycemia, oxidative stress, and inflammation are some of the mechanisms involved in renal damage. Anogeissus acuminata (AA) is used in India as an antidiabetic agent and has potent antioxidant activity. However, it has never been evaluated for its effect on diabetic nephropathy. Hence, in the present study we aimed to evaluate its effect on streptozotocin-induced diabetes mellitus and its renal complications. Methods Diabetes mellitus was induced by injecting streptozotocin, 50 mg/kg, i.p. in rats fasted for 6 h. Rats with hyperglycemia were treated with extracts of AA for 8 weeks at doses of 100 and 300 mg/kg, orally. Human NPH insulin (4 IU/kg, s.c.) was used as standard treatment. Plasma glucose levels (at weeks 1, 2, 4, and 8) and oxidative stress parameters (at weeks 2 and 4) were assessed. Effect on diabetic nephropathy was evaluated by recording the urinary volume, urinary protein excretion, kidney weights, serum creatinine, and blood urea nitrogen levels at week 8. Results Methanolic extract of AA leaves produced statistically significant (p<0.05) hypoglycemic and antioxidant effect. It also resulted in improved urinary function, reflected by better urinary volume and reduced protein excretion in urine. AA treatment could prevent the elevation of serum creatinine and blood urea nitrogen level in a dose-dependent manner. Kidney hypertrophy could be attenuated remarkably, as reflected by the significantly lower kidney weight (KW) per 100 g body weight (p<0.05). Conclusions AA leaf extract attenuated the development of diabetic nephropathy and also demonstrated antidiabetic and antioxidant action.

2020 ◽  
Vol 10 ◽  
Author(s):  
Dhrubajyoti Sarkar ◽  
Sekhar Kumar Bose ◽  
Tania Chakraborty ◽  
Souvik Roy

Background: Diabetic nephropathy (DN), a microvascular complication of diabetes has been a significant health issue globally. However, theaflavin enriched black tea extract (BTE-TF) could restrain DN. Objective: The main objective of this exploration was to elucidate the effect of BTE-TF on DN, though the underlying mechanism remains unclear and requires further investigation. Method: The tea leaves were fermented to get black tea extract. Total phenolic content and HPLC were carried out to determine the phenolic content and theaflavin in the extract. Streptozotocin induced diabetic rats were treated with 100, 200, and 400 mg/kg/day BTE-TF extract for 12 weeks. Biochemical parameters like blood glucose, creatinine, blood urea nitrogen (BUN), triglyceride and antioxidant parameters of kidney tissue were measured. Histology, immunohistochemistry and TUNEL assay were performed to observe the effect of the extract with comparison to the standard drug (Metformin 200mg/kg/day). Result: Treated animals exhibited reduced blood glucose levels, blood urea nitrogen (BUN), creatinine, and serum triglycerides. Further, BTE-TF restored the histological alterations in the kidney. Chronic hyperglycaemia resulted in a significant increase in oxidative stress and pro-inflammatory cytokines of NF-kβ pathway. BTE-TF attenuated oxidative stress (p<0.01), inflammation (p<0.05) and apoptosis (p<0.05). Conclusion: This study suggests that BTE-TF exerts a protective role against diabetes-induced renal injury by ameliorating oxidative stress, inflammation, and apoptosis.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Xu Zhou ◽  
Qingni Wu ◽  
Yanping Wang ◽  
Qing Ren ◽  
Weifeng Zhu ◽  
...  

Objective. This systematic review aims to investigate the efficacy and safety of moxibustion for chronic kidney disease (CKD). Methods. Nine databases were searched to identify relevant evidence up to March 8, 2020. Randomized controlled trials (RCTs) that tested moxibustion + basic treatments versus basic treatments alone for patients with CKD and reported, at least, one of the outcomes of interest were included. In the meta-analyses, the mean differences (MDs) and 95% confidence intervals (CIs) were used to measure the effect size. Results. Twenty-three RCTs (n = 1571) with a moderate to high risk of bias were included. The pooled estimates showed that compared with the controls, patients after moxibustion had a significant reduction in serum creatinine (MD −17.34 μmol/L, 95% CI −28.44 to −6.23; I2 = 87%), 24-hour urine protein excretion (MD −0.75 g/h, 95% CI −1.07 to −0.42; I2 = 84%), and blood urea nitrogen (MD −0.63 mmol/L, 95% CI −1.09 to −0.18; I2 = 37%) and a significant improvement in the quality of life (MD 10.18, 95% CI 3.67 to 16.69; I2 = 57%). Moxibustion did not show a significant effect on the estimated glomerular filtration rate (eGFR), creatinine clearance, or hemoglobin. The subgroup analyses showed that a longer course of moxibustion (>8 weeks) and indirect moxibustion had a greater effect on reducing serum creatinine. The effect of moxibustion on blood urea nitrogen changed to be nonsignificant after excluding RCTs with a high risk of bias (MD −0.96 mmol/L, 95% CI −2.96 to 1.03). Only one adverse event of burn was reported. Conclusions. This systematic review suggests that, as an adjuvant therapy, moxibustion may improve serum creatinine, urinary protein excretion, blood urea nitrogen, and quality of life in patients with CKD. Moxibustion may not have effects on eGFR, creatinine clearance, or hemoglobin. The quality of evidence is weakened by the limitations of risk of bias, heterogeneity, and imprecision.


2018 ◽  
Vol 45 (5) ◽  
pp. 1747-1758 ◽  
Author(s):  
Yingli Jia ◽  
Jinzhao He ◽  
Liang Wang ◽  
Limin Su ◽  
Lei Lei ◽  
...  

Background/Aims: A sodium-glucose co-transporter-2 inhibitor dapagliflozin is widely used for lowering blood glucose and its usage is limited in type 2 diabetes mellitus patients with moderate renal impairment. As its effect on kidney function is discrepant and complicated, the aim of this study is to determine the effect of dapagliflozin on the progression of diabetic nephropathy and related mechanisms. Methods: Twelve-week-old male C57BL/6 wild-type and db/db mice were treated with vehicle or 1 mg/kg dapagliflozin for 12 weeks. Body weight, blood glucose, insulin tolerance, glucose tolerance, pyruvate tolerance and 24-hour urine were measured every 4 weeks. At 24 weeks of age, renal function was evaluated by blood urea nitrogen level, creatinine clearance, urine output, urinary albumin excretion, Periodic Acid-Schiff staining, Masson’s trichrome staining and electron microscopy. Changes in insulin signaling and gluconeogenic key regulatory enzymes were detected using Western blot analysis. Results: Dapagliflozin did not alleviate but instead aggravated diabetic nephropathy manifesting as increased levels of microalbuminuria, blood urea nitrogen, and glomerular and tubular damage in db/db mice. Despite adequate glycemic control by dapagliflozin, urinary glucose excretion increased after administration before 24 weeks of age and was likely associated with renal impairment. Increased urinary glucose excretion was mainly derived from the disturbance of glucose homeostasis with elevated hepatic and renal gluconeogenesis induced by dapagliflozin. Although it had no effect on insulin sensitivity and glucose tolerance, dapagliflozin further induced the expression of gluconeogenic key rate-limiting enzymes through increasing the expression levels of FoxO1 in the kidney and liver. Conclusion: These experimental results indicate that dapagliflozin aggravates diabetes mellitus-induced kidney injury, mostly through increasing gluconeogenesis.


Author(s):  
Preethi G Pai ◽  
Ahsan Shoeb ◽  
P Gokul ◽  
Srinivas Teerthanath

AIM: The present study was undertaken to evaluate noni fruit juice for its protective effects on gentamicin-induced nephrotoxicity in rats. METHODS:Wistar albino rats of either sex, weighing 150-200g were divided into 4 groups; normal saline, gentamicin 80 mg/kg, i.p.,i for 8 days, noni fruit juice 5 and 10 mg/kg, p.o., for 8 days, noni fruit juice 3 days prior and concurrently with gentamicin for 5 days. Blood urea, serum creatinine, serum uric acid and blood urea nitrogen analyses and microscopic examination of kidney were performed after the treatment. RESULTS: Gentamicin treatment caused nephrotoxicity as evidenced by marked elevation in blood urea and serum creatinine. Serum urea, serum uric acid, serum creatinine and blood urea nitrogen were increased with gentamicin compared to saline-treated animals (162.33 ± 9.92mg/dl, 3.13 ± 0.12 mg/dl, 6.85 ± 0.35 mg/dl and 75.86 ± 4.64 mg/dl respectively).Co-administration of noni fruit juice with gentamicin decreased the rise in in these parameters in a dose dependent manner. Study of renal morphology by light microscope showed epithelial loss with intense granular degeneration involving >50% renal cortex in gentamicin treated rats, whereas in noni fruit juice plus gentamicin treated rat revealed insignificant changes in tubular epithelium. CONCLUSION: To conclude, our data suggest that supplementation of noni fruit juice may be useful in reducing gentamicin nephrotoxicity in rats.


2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Preethi G. Pai ◽  
Savindika Chamari Nawarathna ◽  
Avdhooth Kulkarni ◽  
Umma Habeeba ◽  
Sudarshan Reddy C. ◽  
...  

The present study evaluates the nephroprotective effects of ursolic acid in a murine model of gentamicin induced renal damage. Wistar albino rats of either sex, weighing 150–200 g were divided into 5 groups; normal saline, gentamicin 80 mg/kg, intraperitoneally for 8 days, ursolic acid at 2, 5, and 10 mg/kg, per oral for 8 days, ursolic acid administered 3 days prior and concurrently with gentamicin for 5 days. Blood urea, serum creatinine, uric acid and blood urea nitrogen analyses and microscopic examination of kidney were performed. Gentamicin treatment caused nephrotoxicity as evidenced by marked elevation in serum urea, serum uric acid, serum creatinine and blood urea nitrogen (162.33 ± 9.92 mg/dL, 3.13 ± 0.12 mg/dL, 6.85 ± 0.35 mg/dL and 75.86 ± 4.64 mg/dL; resp.) when compared to the saline treated groups. Co-administration of ursolic acid with gentamicin decreased the rise in these parameters in a dose dependent manner. Histopathological analysis revealed epithelial loss with intense granular degeneration in gentamicin treated rats, whereas ursolic acid mitigated the severity of gentamicin-induced renal damage. To conclude, our data suggest that ursolic acid exhibits renoprotective effect in gentamicin induced renal damage and further studies on its mechanis of action are warranted.


2021 ◽  
Vol 11 ◽  
Author(s):  
Qian Zhang ◽  
Xinhua Xiao ◽  
Jia Zheng ◽  
Ming Li ◽  
Miao Yu ◽  
...  

Diabetic nephropathy is a severe microvascular complication of diabetes. Qishen Yiqi dripping pill (QYDP) has been reported to be a renal protective drug. However, the mechanisms remain unclear. This study was performed to investigate the mechanisms. In this study, Sprague-Dawley rats were injected with streptozotocin to generate a diabetes model. Diabetic rats were administered 150 or 300 mg/kg/day QYDP. After 8 weeks of treatment, serum creatinine, serum blood urea nitrogen, and 24-h urinary albumin were measured. Kidney histological staining and immunostaining were analyzed. Then, the renal tissue was analyzed with a genome expression array. The results showed that QYDP treatment reduced serum creatinine, blood urea nitrogen, and 24-h urinary albumin and improved kidney histology and fibrosis. The gene array revealed that the expression of 189 genes was increased, and that of 127 genes was decreased in the high dosage QYDP group compared with the diabetic group. Pathway and gene ontology analyses showed that the differentially expressed genes were involved in the Wnt/β-catenin and transforming growth factor-β (TGF-β)/Smad2 signaling pathways. QYDP reduced the renal Wnt1, catenin β1, Tgfb1, and Smad2 gene expression and β-catenin, TGF-β, Smad2, collagen I, α-smooth muscle actin, and fibronectin protein expression in diabetic rats. Our results provide the first evidence that QYDP performs its renal-protective function by inhibiting the Wnt/β-catenin and TGF-β/Smad2 signaling pathways in diabetic rats.


2018 ◽  
Vol 314 (3) ◽  
pp. F462-F470 ◽  
Author(s):  
Yoshifumi Kurosaki ◽  
Akemi Imoto ◽  
Fumitaka Kawakami ◽  
Masanori Yokoba ◽  
Tsuneo Takenaka ◽  
...  

Megalin, an endocytic receptor expressed in proximal tubule cells, plays a critical role in renal tubular protein reabsorption and is associated with the albuminuria observed in diabetic nephropathy. We have previously reported increased oxidant production in the renal cortex during the normoalbuminuric stage of diabetes mellitus (DM); however, the relationship between oxidative stress and renal megalin expression during the normoalbuminuric stage of DM remains unclear. In the present study, we evaluated whether oxidative stress affects megalin expression in the normoalbuminuric stage of DM in a streptozotocin-induced diabetic rat model and in immortalized human proximal tubular cells (HK-2). We demonstrated that increased expression of renal megalin accompanies oxidative stress during the early stage of DM, before albuminuria development. Telmisartan treatment prevented the diabetes-induced elevation in megalin level, possibly through an oxidative stress-dependent mechanism. In HK-2 cells, hydrogen peroxide significantly increased megalin levels in a dose- and time-dependent manner; however, the elevation in megalin expression was decreased following prolonged exposure to severe oxidative stress induced by 0.4 mmol/l hydrogen peroxide. High-glucose treatment also significantly increased megalin expression in HK-2 cells. Concurrent administration of the antioxidant N-acetyl-cysteine blocked the effects of high glucose on megalin expression. Furthermore, the hydrogen peroxide-induced increase in megalin expression was blocked by treatment with phosphatidylinositol 3-kinase and Akt inhibitors. Increase of phosphorylated Akt expression was also seen in the renal cortex of diabetic rats. Taken together, our results indicate that mild oxidative stress increases renal megalin expression through the phosphatidylinositol 3-kinase-Akt pathway in the normoalbuminuric stage of DM.


Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3373
Author(s):  
Arnold Markovics ◽  
Attila Biró ◽  
Andrea Kun-Nemes ◽  
Mónika Éva Fazekas ◽  
Anna Anita Rácz ◽  
...  

Diabetes mellitus (DM)-related morbidity and mortality are steadily rising worldwide, affecting about half a billion people worldwide. A significant proportion of diabetic cases are in the elderly, which is concerning given the increasing aging population. Proper nutrition is an important component in the effective management of diabetes in the elderly. A plethora of active substances of plant origin exhibit potency to target the pathogenesis of diabetes mellitus. The nutraceutical and pharmaceutical effects of anthocyanins have been extensively studied. In this study, the effect of Hungarian sour cherry, which is rich in anthocyanins, on hyperglycemia-induced endothelial dysfunction was tested using human umbilical cord vein endothelial cells (HUVECs). HUVECs were maintained under both normoglycemic (5 mM) and hyperglycemic (30 mM) conditions with or without two concentrations (1.50 ng/µL) of anthocyanin-rich sour cherry extract. Hyperglycemia-induced oxidative stress and inflammatory response and damaged vasorelaxation processes were investigated by evaluating the level of reactive oxygen species (ROS) and gene expression of four proinflammatory cytokines, namely, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1α (IL-1α), as well as the gene expression of nitric oxide synthase (NOS) endothelin-1 (ET-1) and endothelin-converting enzyme-1 (ECE-1). It was found that hyperglycemia-induced oxidative stress was significantly suppressed by anthocyanin-rich sour cherry extract in a concentration-dependent manner. The gene expression of the tested proinflammatory cytokines increased under hyperglycemic conditions but was significantly reduced by both 1 and 50 ng/µL anthocyanin-rich sour cherry extract. Further, although increased ET-1 and ECE-1 expression due to hyperglycemia was reduced by anthocyanin-rich sour cherry extract, NOS expression was increased by the extract. Collectively, these data suggest that anthocyanin-rich sour cherry extract could alleviate hyperglycemia-induced endothelial dysfunction due to its antioxidant, anti-inflammatory, and vasorelaxant effects.


2016 ◽  
Vol 41 (3) ◽  
pp. 125-130
Author(s):  
Mahbuba Shirin ◽  
Mofazzal Sharif ◽  
Ayeshna Gurung ◽  
Anindita Datta

Diabetes mellitus is one of the systemic diseases affecting the kidneys. Diabetic nephropathy is a serious microvascular complication of diabetes mellitus. It is the most important cause of death in type I diabetic patients, of whom 30%-40% eventually develop end-stage renal failure and 40% of type II diabetics are at risk of developing diabetic nephropathy. So, diagnosis of diabetic nephropathy is paramount for the survivability of the diabetic patients not only because of the consequences of renal progression but also because of the strong association with the risk of developing cardiovascular disease. A total number of 53 subjects were enrolled in this present cross sectional study in the department of Radiology and Imaging, Bangabandhu Sheikh Mujib Medical University (BSMMU) in collaboration of Nephrology and Medicine of the same institution during two years (2011-13) aim to evaluate the diagnostic usefulness of renal resistive index (RI) by duplex Doppler ultrasonography for detection of renal dysfunction in diabetic patients. Clinically diagnosed diabetic patients having diabetic nephropathy referred to the department of Radiology and Imaging in BSMMU for ultrasonography of Kidneys, Ureters and Bladder (KUB) region or whole abdomen were selected as sample. Biochemical reports (Serum creatinine and Urinary albumin) and the RI value of intrarenal artery were correlated and analyzed. Only those patients biochemically were diagnosed as having diabetic nephropathy was included. Those with incomplete data, hydro nephrosis and renal calculus were excluded. Both the kidneys were visualized by commercially available real time scanner (GE Voluson) equipped with a curvilinear transducer operating at 3.5 MHz First Gray scale ultrasonography was done followed by Color Doppler of intra renal artery and then RI was measured. Majority (45.3%) patients were in 6th decade with the mean age was of 52.66±7.4 years and ranging from 38 to 65 years in patients. Male was found to be 54.7% of diabetic patients with male to female ratio 1.2:1. Resistive index of (? 0.7) was found in 73.6% patients with diabetes with the mean resistive index of 0.71±0.04. Positive correction between resistive index with serum creatinine (r=0.581, p<0.01) and albuminuria (r=0.725, p<0.01) were observed. It can be concluded that Resistive Index measured by duplex Doppler ultrasonography is useful diagnostic modality for detection of renal dysfunction in diabetic nephropathy patients. Resistive Index has value in identifying diabetic patients who are developing nephropathy and can be used as an additional diagnostic tool. Also it is well correlated with Serum Creatinine and Albuminuria which are the biochemical parameters to diagnose diabetic nephropathy.


2008 ◽  
Vol 27 (3) ◽  
pp. 376-382 ◽  
Author(s):  
Tatjana Cvetković ◽  
Predrag Vlahović ◽  
Vidosava đorđević ◽  
Lilika Zvezdanović ◽  
Dušica Pavlović ◽  
...  

The Significance of Urinary Markers in the Evaluation of Diabetic Nephropathy Oxidative stress is considered to be a unifying link between diabetes mellitus (DM) and its complications, including nephropathy (DN). The aim of this study was to determine the parameters of oxidative injury of lipids and proteins as well as the activity of ectoenzymes in the urine of DN patients. The study included 40 individuals: 10 patients with type 2 diabetes mellitus and microalbuminuria (DMT2-MIA), 10 type 2 diabetic patients with macroalbuminuria (DMT2-MAA), 10 patients with type 1 diabetes and microalbuminuria (DMT1-MIA) and 10 age- and sex-matched healthy subjects (control). In the urine we determined TBA reactive substances (TBARS), reactive carbonyl groups (RCG), and the activity of ectoenzymes N-acetyl-β-d-glucosaminidase (NAG), plasma cell differentiation antigen (PC-1), aminopeptidase N (APN) and dipeptidyl peptidase IV (DPP IV). A higher concentration of TBARS in the urine was found in DMT2-MIA and DMT1-MIA, compared to the control group (p<0.001 and P<0.05). The urine concentration of RCD shows similar results with a significant elevation in the groups with DMT2-MAA and DMT1-MIA, compared to the DMT2-MIA (p<0.001) and control group (p<0.001). Activities of NAG, APN and DPPIV were significantly higher in the urine of DMT2-MAA, compared to the control (p<0.01). The activity of PC-1 was slightly increased in that group, but not significantly. In conclusion, the level of oxidative stress markers and activities of brush border ectoenzymes in the urine may be a useful non-invasive and easily repeatable test in DN.


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