scholarly journals Nephroprotective Effect of Coenzyme Q10 alone and in Combination with N-acetylcysteine in Diabetic Nephropathy

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
S. Mahajan Manojkumar ◽  
B. Upaganlawar Aman ◽  
D. Upasani Chandrashekar

Abstract Aim Oxidative stress due to chronic hyperglycaemia is a key factor in the development and progression of various microvascular complications including diabetic nephropathy (DN) and associated renal injury. Treatment with antioxidants is one of the strategies to protect the kidney from oxidative tissue damage to improve renal physiology during DN. The investigation, therefore, was designed to assess the nephroprotective effect of coenzyme Q10 (CoQ10) and N-acetylcysteine (NAC), either alone or in combination in streptozotocin (STZ)-nicotinamide (NAD) induced diabetic nephropathy (DN) in rats. Methods T2DM induced by STZ (55 mg/kg, i.p.)-NAD (110 mg/kg, i.p.) in Sprague-Dawley rats (220–250 g) was confirmed by the elevated blood glucose level and glycated haemoglobin. DN was assessed by renal function tests. The diabetic rats were treated with CoQ10 (10 mg/kg, p.o.) and/or NAC (300 mg/kg, p.o.) for 8 weeks after confirmation of DN. Oxidative tissue damage due to STZ-NAD was estimated by malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT), reduced glutathione (GSH), myeloperoxidase (MPO) and nitric oxide (NO) in the renal homogenate. Results Data showed significant alteration in serum and urinary creatinine, total protein, albumin, serum urea, blood urea nitrogen (BUN) and uric acid in diabetic animals as compared to the control rats. CoQ10 and/or NAC effectively alleviated the disturbances in renal function. Diabetic rats showed increased MDA, decreased SOD and CAT activities and decreased GSH along with a significant increase in MPO activity and nitrite content. Treatment with the aforementioned antioxidants and their combination ameliorated the kidney damage as indicated by the reduced OS with improved renal function. Conclusion The investigation suggests that the chronic hyperglycaemia-induced OS leads to the development and progression of DN. The combined treatment with CoQ10 and NAC has shown a remarkable nephroprotective effect suggesting that combined antioxidant therapy with CoQ10 and NAC may be useful in the attenuation of DN.

2021 ◽  
Vol 14 ◽  
Author(s):  
Amal M. Youssef ◽  
Dalia A. Mohamed ◽  
Samia Hussein ◽  
Doaa M. Abdullah ◽  
Shaimaa A. Abdelrahman

Background: Diabetes mellitus (DM) affects the musculoskeletal system through its metabolic perturbations. Exercise modulates blood sugar levels and increases the body’s sensitivity to insulin in patients with DM. Objective: This study aimed to investigate the potential effects of combined quercetin and coenzyme Q10 (CoQ10) supplements with or without exercise on the histological, biochemical and molecular structures of diabetic rat’s skeletal muscle. Method: A total of 64 adult male albino rats were divided into six groups: control, trained nondiabetic, non-trained diabetic, diabetic rats treated with combined CoQ10 and quercetin, diabetic rats with treadmill training, and diabetic rats treated with treadmill training and CoQ10 and quercetin. Blood and skeletal muscle samples were obtained from all groups for routine histological examination and biochemical determination of cytokine levels and protein activities. Quantitative real-time polymerase chain reaction (qRT-PCR) and morphometric analysis of PAS and Bax expressions were also performed. Results: Biochemical analysis revealed improvement in all studied parameters with combined CoQ10 and quercetin than exercise training alone. Combined treatment and exercise showed significant improvement in all parameters especially interleukin 6 and malondialdehyde. Fibronectin type III domain-containing protein 5 (FNDC5) expression and irisin levels increased in all trained groups but combined treatment with exercise significantly increased their levels than exercise alone. Histological analysis revealed improvement after exercise or combined treatment; however, when exercise was combined with CoQ10 and quercetin, marked improvement was observed. Conclusion: the combination of CoQ10 and quercetin could be promising in preserving musculoskeletal function in patients with DM concomitantly with physical exercise.


Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 890-898 ◽  
Author(s):  
Chen Jihua ◽  
Chen Cai ◽  
Bao Xubin ◽  
Yu Yue

AbstractObjectiveTo investigate the effects and mechanisms of dexmedetomidine (Dex) on model rats of diabetic nephropathy (DN).MethodsRats were divided into NC, model, Dex-L (1μg/ kg), Dex-M (5μg/kg) and Dex-H (10μg/kg) groups. Rats in all groups except in the NC group were injected with streptozotocin (STZ) combined with right nephrectomy. Rats in Dex (1, 5 and 10μg/kg) groups received gavage with Dex (1, 5 and 10μg/kg). After 4 weeks, rats were sacrificed and kidneys were collected. HE staining was performed for a renal injury. Masson staining was applied to detect the fibrotic accumulation in rat kidney. Radioimmunoassay was used to test the renal function. Immunohistochemical method was used to detect protein expressions of RhoA, p-MYPT and Nox4 in rat kidney.ResultsCompared with the NC group, the levels of urine microalbumin in protein, α1-MG and β2-MG, renal fibrotic accumulation, RhoA, p-MYPT, Nox4 and α-SMA in model group increased significantly (P<0.001, respectively). Compared with the model group, Dex low, medium and high groups improved the deposition of renal fiber in rats, inhibited the expression levels of microalbumin, α1-MG and β2-MG in urine and decreased expression of RhoA, p-MYPT, Nox4 and α-SMA proteins (P<0.05, P<0.01).ConclusionDex is possible to inhibit the expression of α-SMA and renal fibrous substance deposition in rat kidney via RhoA/ROCK/Nox4 signaling pathway, thereby reducing early kidney damage in model rats.


2008 ◽  
Vol 36 (03) ◽  
pp. 517-540 ◽  
Author(s):  
Viduranga Y. Waisundara ◽  
Annie Hsu ◽  
Dejian Huang ◽  
Benny Kwong-Huat Tan

Oxidative stress is the root cause of diabetic macro- and microvascular complications. Biochemical and epidemiological studies indicate that current treatments for diabetes do not reduce risks of developing complications, suggesting their inability to alleviate the levels of oxidative stress. This study in streptozotocin (STZ)-induced diabetic rats was carried out to investigate the effect of combining the antidiabetic drug, metformin, with an ethanolic extract of Scutellaria baicalensis, a plant whose root is known for its radical scavenging activity. Three groups of STZ-induced diabetic rats were given the following treatments for 30 days: (1) metformin 500 mg/kg, (2) S. baicalensis 400 mg/kg, (3) metformin 500 mg/kg + S. baicalensis extract 400 mg/kg. In addition, vehicle-treated diabetic and nondiabetic controls were used in the experiment. The rats treated with S. baicalensis and metformin + S. baicalensis had elevated hepatic activities of the antioxidant enzymes — superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) compared to the vehicle- and metformin-treated diabetic groups ( p < 0.05). Plasma and hepatic lipid peroxide concentrations in the herb-treated and herb + metformin-treated groups were also significantly reduced ( p < 0.05). In addition, the combined treatment caused significant elevations of plasma and pancreatic insulin levels and reductions of plasma and hepatic triglycerides (TG) and cholesterol levels. The study thus showed that S. baicalensis enhanced the antidiabetic effect of metformin in STZ-induced diabetic rats by improving the antioxidant status. It also increased pancreatic insulin content as well as improved the lipid profile in these rats.


Author(s):  
Alok Shiomurti Tripathi ◽  
Papiya Mitra Mazumder ◽  
Anil Vilasrao Chandewar

AbstractThe present study evaluates the possible mechanism of sildenafil citrate (SIL) for the attenuation of renal failure in diabetic nephropathic (DN) animals.Diabetic nephropathy was induced by a single dose of streptozotocin (STZ) (60 mg/kg, i.p.) and confirmed by assessing the blood and urine biochemical parameters on the 28th day of its induction. The selected DN animals were treated with glimepiride (0.5 mg/kg, p.o.) and SIL (2.5 mg/kg, p.o.) for a period of 6 weeks. Biochemical parameters in blood and urine were estimated after the 29th and 70th day of the protocol for the estimation of the effect of SIL.There were significant alterations in the blood and urine biochemical parameters in STZ-treated groups which confirmed DN. There was a significant decrease in the triglyceride level in the SIL-only-treated group on the 70th day of the protocol. The histopathology study also suggested that SIL treatment results in the improvement in the podocyte count in DN animals.The present study concludes that SIL improves the renal function by decreasing the triglyceride level and improving the podocyte count in DN animals.


2017 ◽  
Vol 8 (4) ◽  
Author(s):  
Ambily Scaria ◽  
Jagadhish V Kamath ◽  
Manodeep Chakraborty

Objective: The present study aimed to evaluate in vivo the antihyperglycemic, anti oxidant,antihyperlipidemic and nephroprotective effects of Stevioside against Alloxan induced diabetic nephropathy in rats. Materials and Methods: In this model diabetes was induced using Alloxan (125 mg/kg, i.p) and the prophylactic treatment was started 48 hours after Alloxan injection for 28 days. The protective effect of the treatment with standard (Glibenclamide 0.5mg/kg, p.o) and Stevioside (250 mg/kg. p.o) were analyzed by estimating the serum levels of glucose, urea, creatinine, albumin, total protein, total cholesterol (TCH), triglycerides (TG), high density lipoproteins (HDL) and antioxidants like SOD, catalase and lipid peroxidation. Key Findings: This study demonstrates that Stevioside improved hyperglycemia and maintained antioxidant status and reduced total cholesterol, TG, urea, creatinine and albumin and lipid peroxidation levels when compared to toxic control. The protective effect of Stevioside against Alloxan induced diabetic nephropathy in rats was also supported by histopathologic findings.The results of the present study are encouraging for its potential use to delay the onset and progression of diabetic renal complications. However, the translation of therapeutic efficacy in humans requires further studies.


2021 ◽  
Vol 5 (01) ◽  
pp. 19-22
Author(s):  
Miranda Jemyma Mas'ulun ◽  
Arifa Mustika ◽  
Ema Qurnianingsih

Changes in kidney homeostasis due to diabetes can cause oxidative stress which then caused tissue damage that leads to diabetic nephropathy. Clinacanthus nutans extract is known to contain antioxidants that are reported to play an important role in the body’s defense system against oxidative stress to minimize tissue damage. This study aims to know the effect of Clinacanthus nutans leaf extract administration on kidney histopathological features of the diabetic rats model. A total of 35 rats were induced by streptozotocin which then divided into 5 groups and given Clinacanthus nutans extract with a dose of 75 mg/kgBW, 150 mg/kgBW and 300 mg/kgBW then compare with CMC-Na as control and metformin as standard drug for 14 days. The kidney histopathology was evaluated under a light microscope against the damage criteria that occurred in the proximal tubules of the kidney. As the result the least amout of kidney damage was on treatment group at dose 300 mg/kgBW, followed by extract with dose 75 mg/kgBW, 150 mg/kgBW, and metformin. In conclusion Clinacanthus nutans extract with a dose of 75 mg/kgBW, 150 mg/kgBW, and 300 mg/kgBW can improve the kidney histopathological feature of the diabetic rats model. Keywords: diabetes mellitus; histopathology; diabetic nephropathy; Clinacanthus nutans


1995 ◽  
Vol 269 (3) ◽  
pp. F429-F438 ◽  
Author(s):  
H. Trachtman ◽  
S. Futterweit ◽  
J. Maesaka ◽  
C. Ma ◽  
E. Valderrama ◽  
...  

We examined the effect of two endogenous antioxidant agents, taurine and vitamin E, on renal function in experimental diabetes. Male Sprague-Dawley rats, rendered diabetic with streptozocin (STZ), were assigned to one of the following groups: 1) untreated; 2) insulin treatment with 6 U Ultralente insulin/day in two doses; 3) taurine supplementation by 1% taurine in drinking water; and 4) vitamin E supplementation at 100 IU vitamin E/kg chow. Animals were kept for 52 wk. The survival rate was similar (70-90%) in all groups except vitamin E-treated animals, of which 84% died by 6 mo. At 52 wk, glomerular filtration rate was elevated in untreated and taurine-treated STZ rats compared with normal or insulin-treated diabetic rats. Taurine supplementation reduced total proteinuria and albuminuria by nearly 50%. This treatment also prevented glomerular hypertrophy, preserved immunohistochemical staining for type IV collagen in glomeruli, and diminished glomerulosclerosis and tubulointerstitial fibrosis in diabetic animals. The changes in renal function and structure in taurine-treated diabetic rats were associated with normalization of renal cortical malondialdehyde content, lowering of serum free Fe2+ concentration, and decreased formation of the advanced glycooxidation products, pentosidine, and fluorescence in skin collagen. Administration of the vitamin E-enriched diet exacerbated the nephropathy in STZ-diabetic rats. In addition, vitamin E supplementation increased serum free Fe2+ concentration, enhanced renal lipid peroxidation, and accelerated the accumulation of advanced glycosylation end products (AGEs) in skin collagen. We conclude that administration of taurine, but not vitamin E, to rats with STZ-diabetes ameliorates diabetic nephropathy. The beneficial effect of taurine is related to reduced renal oxidant injury with decreased lipid peroxidation and less accumulation of AGEs within the kidney.


2012 ◽  
Vol 23 (2) ◽  
pp. 443-449 ◽  
Author(s):  
Haseena Banu Hedayathullah Khan ◽  
Kanchana Karvannan ◽  
G. Deepa ◽  
Shanthi Palanivelu ◽  
Sachdanandam Panchanadham

Author(s):  
Jamal Amri ◽  
Mona Alaee ◽  
Seyed Amirhossein Latifi ◽  
Abbas Alimoradian ◽  
Mehdi Salehi

Abstract Objectives Type 1 diabetes is one of the most important causes of microvascular complications such as nephropathy. On other hand, the use of herbal medicines is more affordable and has fewer side effects. Therefore, this study was conducted to assessment the therapeutic effect of saffron in diabetic nephropathy by regulating the expression of CTGF and RAGE genes as well as oxidative stress in rats with type 1 diabetes. Methods In this study, we used 24 Wistar rats in four groups. To induce diabetes, we used a 55 mg/kg.bw dose of streptozotocin intraperitoneally. Type 1 diabetic rats were administered saffron (20 and 40 mg/kg/day) by gavage once daily for 42 days. Finally, serum urea, creatinine, albumin and SOD, MDA levels in kidney tissue were measured using spectrophotometric methods and CTGF and RAGE gene expression in kidney tissue was measured using real-time PCR method. Results Diabetes significantly increases serum FBG, urea, creatinine and decreases albumin (p<0.001). AS well as increased the CTGF and RAGE genes expression, MDA level and decreased the SOD activity in the kidney tissue (p<0.001). Serum urea, creatinine, albumin was significantly ameliorated by saffron (p<0.001). It was shown the saffron significantly decrease the kidney expression CTGF and RAGE genes and MDA level and increased the SOD activity (p<0.001). Also, it was found that the beneficial effects of the saffron were dose-dependent (p<0.05). Conclusions The results of this study suggest that saffron as an adjunct therapy may prevent development and treatment of diabetic nephropathy by regulating the expression of the CTGF and RAGE genes and oxidative stress.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fangfang Sun ◽  
Deqi Jiang ◽  
Juanjuan Cai

Abstract Background Diabetic nephropathy (DN) is one of the most serious microvascular complications of diabetes, valsartan and α-lipoic acid alone or in combination has been used for the treatment of patients with DN. However, some results in these clinical reports were still controversial. The purpose of this study was to evaluate the efficacy of valsartan combined with α-lipoic acid on renal function in patients with DN. Methods We searched the electronic databases including PubMed, Sciencedirect, EMBASE, Cochrane library, Chinese national knowledge infrastructure (CNKI) and Wanfang databases, and the publication deadline was limited to January 2020. Randomized controlled trials (RCTs) evaluating the effects of valsartan combined with α-lipoic acid in DN patients were included. Pooled estimates were conducted using a fixed or random effect model. The outcomes included urinary albumin excretion rate (UAER), and the level of urinary albumin, β2-microglobulin (β2-MG), hypersensitive C-reactive protein (hs-CRP) and oxidative stress. Results 11 studies with 1294 participants were included in this study. The pooled analysis indicated that α-lipoic acid combined with valsartan could remarkably reduce UAER (P < 0.00001, SMD = -1.95, 95%CI = -2.55 to − 1.20; P = 0.03, SMD = -0.85, 95%CI = -1.59 to − 0.1) and the level of urinary albumin (P = 0.001, SMD = -1.48, 95%CI = − 2.38 to − 0.58; P = 0.01, SMD = -1.67, 95%CI = -3.00 to − 0.33), β2-MG (P < 0.001,SMD = − 2.59, 95%CI = -3.78 to − 1.40; P = 0.03, SMD = -0.48, 95%CI = -0.93 to − 0.04) when compared with valsartan or lipoic acid monotherapy in patients with DN. However, there was no significant difference in the level of hs-CRP among the three therapies (P = 0.06, SMD = -2.80, 95%CI = -5.67 to 0.07; P = 0.10, SMD = -0.42, 95%CI = − 0.92 to 0.08). In addition, α-lipoic acid combined with valsartan markedly increased the level of SOD (P = 0.03, SMD = 1.24, 95%CI = 0.32 to 1.03; P = 0.0002, SMD = 0.68, 95%CI = 0.32 to 1.03) and T-AOC (P < 0.00001, SMD = 0.89, 95%CI = 0.62 to 1.16; P = 0.02, SMD = 0.58, 95%CI = 0.10 to1.07), and reduced the level of MDA(P = 0.0002, SMD = -1.99, 95%CI = -3.02 to − 0.96; P = 0.0001, SMD = -0.69, 95%CI = -1.04 to − 0.34). Conclusions α-lipoic acid combined with valsartan could significantly reduce the level of urinary albumin and oxidative stress, increase antioxidant capacity and alleviate renal function damage in patients with DN, and this will provide a reference for the selection of treatment drugs for DN.


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