scholarly journals Anion Gap Toxicity in Alloxan Induced Type 2 Diabetic Rats Treated with Antidiabetic Noncytotoxic Bioactive Compounds of Ethanolic Extract of Moringa oleifera

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Maxwell Omabe ◽  
Chibueze Nwudele ◽  
Kenneth Nwobini Omabe ◽  
Albert Egwu Okorocha

Moringa oleifera (MO) is used for a number of therapeutic purposes. This raises the question of safety and possible toxicity. The objective of the study was to ascertain the safety and possible metabolic toxicity in comparison with metformin, a known drug associated with acidosis. Animals confirmed with diabetes were grouped into 2 groups. The control group only received oral dose of PBS while the test group was treated with ethanolic extract of MO orally twice daily for 5-6 days. Data showed that the extract significantly lowered glucose level to normal values and did not cause any significant cytotoxicity compared to the control group (P=0.0698); there was no gain in weight between the MO treated and the control groups (P>0.8115). However, data showed that treatment with an ethanolic extract of MO caused a decrease in bicarbonate (P<0.0001), and more than twofold increase in anion gap (P<0.0001); metformin treatment also decreased bicarbonate (P<0.0001) and resulted in a threefold increase in anion gap (P<0.0001). Conclusively, these data show that while MO appears to have antidiabetic and noncytotoxic properties, it is associated with statistically significant anion gap acidosis in alloxan induced type 2 diabetic rats.

2020 ◽  
Vol 20 (7) ◽  
pp. 1117-1132
Author(s):  
Abdelaziz M. Hussein ◽  
Elsayed A. Eid ◽  
Ismaeel Bin-Jaliah ◽  
Medhat Taha ◽  
Lashin S. Lashin

Background and Aims: In the current work, we studied the effects of exercise and stevia rebaudiana (R) extracts on diabetic cardiomyopathy (DCM) in type 2 diabetic rats and their possible underlying mechanisms. Methods: : Thirty-two male Sprague Dawley rats were randomly allocated into 4 equal groups; a) normal control group, b) DM group, type 2 diabetic rats received 2 ml oral saline daily for 4 weeks, c) DM+ Exercise, type 2 diabetic rats were treated with exercise for 4 weeks and d) DM+ stevia R extracts: type 2 diabetic rats received methanolic stevia R extracts. By the end of the experiment, serum blood glucose, HOMA-IR, insulin and cardiac enzymes (LDH, CK-MB), cardiac histopathology, oxidative stress markers (MDA, GSH and CAT), myocardial fibrosis by Masson trichrome, the expression of p53, caspase-3, α-SMA and tyrosine hydroxylase (TH) by immunostaining in myocardial tissues were measured. Results: T2DM caused a significant increase in blood glucose, HOMA-IR index, serum CK-MB and LDH, myocardial damage and fibrosis, myocardial MDA, myocardial α-SMA, p53, caspase-3, Nrf2 and TH density with a significant decrease in serum insulin and myocardial GSH and CAT (p< 0.05). On the other hand, treatment with either exercise or stevia R extracts significantly improved all studied parameters (p< 0.05). Moreover, the effects of stevia R was more significant than exercise (p< 0.05). Conclusion: Both exercise and methanolic stevia R extracts showed cardioprotective effects against DCM and Stevia R offered more cardioprotective than exercise. This cardioprotective effect of these lines of treatment might be due to attenuation of oxidative stress, apoptosis, sympathetic nerve density and fibrosis and upregulation of the antioxidant transcription factor, Nrf2.


2004 ◽  
Vol 287 (3) ◽  
pp. H1225-H1231 ◽  
Author(s):  
Lucilla D. Monti ◽  
Claudio Landoni ◽  
Emanuela Setola ◽  
Elena Galluccio ◽  
Pietro Lucotti ◽  
...  

We evaluated the influence of chronic hypertriglyceridemia and endothelial dysfunction on myocardial glucose uptake (MGU) in Type 2 diabetic patients without coronary heart disease. Patients were divided into two groups according to fasting triglyceride (TG) levels: 5.4 ± 1.1 and 1.5 ± 0.3 mmol/l for high- and normal-TG groups, respectively. Five subjects were assigned to the high-TG group and 11 to the normal-TG group. Age, gender, body mass index, systolic and diastolic blood pressure, glucose, insulin, HbA1c, cholesterol, and HDL cholesterol were similar in the two groups, whereas free fatty acid (FFA) levels were higher in the high-TG group basally and at the end of the clamp. Furthermore, five healthy subjects were subjected to the same protocol and used as the control group. MGU was assessed by using 18F-labeled 2-fluoro-2-deoxy-d-glucose under hyperglycemic-hyperinsulinemic conditions. Basal endothelin-1 and nitric oxide levels were significantly higher in the high-TG group than in the normal-TG and control groups, and cGMP and maximal postischemic vasodilation were significantly decreased in the high-TG group compared with the normal-TG and control groups. However, significant alterations were found in the same parameters in the normal-TG group compared with the control group. By the end of the hyperglycemic clamp, in the high-TG group, MGU was ∼40 and 65% of that in the normal-TG and control groups. MGU negatively correlated with TG, FFA, and endothelin-1, whereas a positive correlation was found with cGMP and maximal postischemic vasodilation. In conclusion, increased TG and FFA levels are risks, in addition to Type 2 diabetes mellitus, for myocardial insulin resistance, endothelial dysfunction, and alteration of nitric oxide/cGMP levels.


2010 ◽  
Vol 38 (04) ◽  
pp. 713-725 ◽  
Author(s):  
Yun-Xia Lu ◽  
Qiu Zhang ◽  
Jun Li ◽  
Yu-Xiu Sun ◽  
Ling-Yun Wang ◽  
...  

This study was initiated to determine the possible antidiabetic effects of total flavonoids of Litsea Coreana leve (TFLC), an alcohol extract from the dried leaves of Litsea Coreana leve, on type 2 diabetic rats. Male Sprague-Dawley rats ( n = 40, 160–180 g) were divided into two groups and fed with normal chow diet (Normal Control group) or high-fat diet (HFD) for a period of 4 weeks. After 4 weeks of dietary manipulation, the HFD-fed rats were injected with 30 mg/kg streptozocin (STZ) to induce diabetes 72 hours after STZ injection. These diabetic rats were randomly divided into 3 groups ( n = 10): Diabetic Control group, Diabetic + TFLC group and Diabetic + PIO group. Diabetic + TFLC group and Diabetic + PIO group were orally administered with 400 mg/kg TFLC or 10 mg/kg pioglitazone (all suspended in 0.5% CMC-Na) respectively for 6 weeks. All rats were examined for body weight, serum and hepatic biochemical indices, content of malondialdehyde (MDA), activities of superoxide dismutase (SOD) and pathological changes in liver and pancreas, as well as protein tyrosine phosphatase 1B (PTP1B) expression in liver. The diabetic rats became obese, insulin resistant, hyperglycemic and hyperlipidemic. Treatment with TFLC showed a significant increase in insulin sensitivity, serum HDL-C level and SOD activities, meanwhile marked decrease in body weight, serum FFA, TC, TG, LDL-C, CRP, MDA content. TFLC also attenuated pathologic alterations in liver and pancreatic islet. Furthermore, TFLC was found to decrease the expression of PTP1B in diabetic rat liver. These results suggested that TFLC could ameliorate hyperglycemia, hyperlipoidemia, inflammation and oxidation stress, as well as insulin resistance of type 2 diabetic rats.


Author(s):  
Shailendra Mishra ◽  
Quazi Shahir Ahmed ◽  
Kauser Sayedda

Background: Dyslipidaemia is an important risk factor for development of macrovascular complications in type 2 diabetes mellitus. Ocimum sanctum (OS) and metformin have shown to have antihyperlipidaemic effects. The present study was undertaken  to evaluate the effects of  OS and Metformin on body weight & plasma lipid  levels of high fat diet fed diabetic ratsMethods: Total of 30 male wistar  rats (100-150gm) were obtained. Animals were fed with a high fat diet throughout the study (6 weeks). Diabetes was induced by using single intra-peritoneal injection of Streptozotocin 50mg/kg at the end of 4 weeks.  Diabetic rats were divided into groups of 6 each and treated as follows: Group 1- Diabetic control, was given vehicle orally. Group 2- O.S. ethanolic extract 100mg/kg body weight orally for 14 days. Group 3- O.S. ethanolic extract  200mg/kg body weight orally for 14 days. Group 4-  Metformin 100mg/day for 14 daysResults: At the end of 4 weeks, body weight of rats were significantly increased (p <0.05). Maximum weight gain was seen in control group whereas weight gain was least in O.S. 200mg/kg group (p >0.05). Decrease in body weight was seen in metformin group. Abdominal circumference of rats also showed similar pattern (p >0.05).  OS 200 caused significant reduction in serum LDL levels (p <0.05) and significant rise of serum HDL levels (p <0.05) as compared to control group. Metformin also favourably affected the lipid profile and its effects were not significantly different from effects of OS 200 (p> 0.05).Conclusions: Present study revealed that Ocimum Sanctum caused significant reduction in serum lipid levels in high fat diet fed diabetic rats. Metformin  also exhibited antihyperlipidaemic activity. So, it is concluded that OS or metformin alone or in combination  could be a novel adjunct to diet and life style modification for the management of dyslipidaemia in type 2 diabetes.  Further studies are required to confirm the antidyslipidaemic activities of individual phytoconstituents of Ocimum sanctum.


2012 ◽  
Vol 40 (04) ◽  
pp. 721-733 ◽  
Author(s):  
Wenfan Huang ◽  
Jie Yu ◽  
Xuming Jia ◽  
Liang Xiong ◽  
Ningxu Li ◽  
...  

Forkhead box O1 (FOXO1) plays an important role in glucose metabolism at the gene transcription level. Increased FOXO1 activity results in hyperglycemia by promoting the expression of gluconeogenic enzymes such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), and inhibiting glucokinase (GK). This study evaluates the effect of Zhenqing Recipe (ZQR), a Chinese herbal medicine, on hyperglycemia and its molecular mechanisms. Type 2 diabetic rats, developed by high-fat diet combined with low-dose STZ injections, were randomly divided into untreated diabetic, ZQR and metformin group. Normal rats served as control. After an eight-week treatment, fasting blood glucose was significantly decreased and insulin sensitivity index was obviously increased in the ZQR group. ZQR also improved the oral glucose tolerance. Compared with the control group, the mRNA levels of PEPCK and G6Pase were significantly elevated, while GK mRNA expression was decreased in the liver of untreated diabetic rats. ZQR significantly reduced the mRNA levels of PEPCK and G6Pase, and increased GK mRNA expression. The hepatic mRNA and protein expression of FOXO1 in the untreated diabetic group was markedly increased compared to controls. The administration of ZQR significantly decreased the mRNA and protein levels of hepatic FOXO1. The data suggest that ZQR improves glucose metabolism and insulin sensitivity, which is accompanied with regulating mRNA expression of GK and gluconeogenic genes. This anti-diabetic effect of ZQR is due to its ability to repress hepatic FOXO1 at the mRNA and protein level.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Li-ping Han ◽  
Chun-jun Li ◽  
Bei Sun ◽  
Yun Xie ◽  
Yue Guan ◽  
...  

Immune and inflammatory pathways play a central role in the pathogenesis of diabetic liver injury. Celastrol is a potent immunosuppressive and anti-inflammatory agent. So far, there is no evidence regarding the mechanism of innate immune alterations of celastrol on diabetic liver injury in type 2 diabetic animal models. The present study was aimed at investigating protective effects of celastrol on the liver injury in diabetic rats and at elucidating the possible involved mechanisms. We analyzed the liver histopathological and biochemical changes and the expressions of TLR4 mediated signaling pathway. Compared to the normal control group, diabetic rats were found to have obvious steatohepatitis and proinflammatory cytokine activities were significantly upregulated. Celastrol-treated diabetic rats show reduced hepatic inflammation and macrophages infiltration. The expressions of TLR4, MyD88, NF-κB, and downstream inflammatory factors IL-1βand TNFαin the hepatic tissue of treated rats were downregulated in a dose-dependent manner. We firstly found that celastrol treatment could delay the progression of diabetic liver disease in type 2 diabetic rats via inhibition of TLR4/MyD88/NF-κB signaling cascade pathways and its downstream inflammatory effectors.


2020 ◽  
Vol 16 (1) ◽  
pp. 68
Author(s):  
Ismawati Ismawati ◽  
Ilhami Romus ◽  
Dhea Ayu Kartini Surya Putri

Kelainan pulau Langerhans (isletopathy) merupakan salah satu komplikasi DM tipe 2. Penelitian mengenai  efek asam alfa lipoat (ALA) terhadap matriks ekstraseluler pankreas (ECM) pada DM tipe 2 masih  terbatas. Penelitian ini bertujuan untuk mengetahui efek ALA terhadap ketebalan kolagen ECM sel β pankreas pada tikus diabetes melitus tipe 2. Penelitian eksperimental dengan design post test only control group design  ini menggunakan 15 ekor tikus Rattus novergicus galur Wistar jantan yang dibagi menjadi tiga kelompok, yaitu kelompok kontrol, kelompok diabetes melitus tipe 2, dan kelompok diabetes melitus tipe 2 yang diberi ALA. Induksi diabetes melitus tipe 2 dilakukan dengan pemberian streptozotosin (50 mg/kgBB) diikuti nikotinamid (110 mg/kgBB) intraperitoneal. Dosis ALA yang digunakan 60 mg/kgBB/hari diberikan selama 3 minggu. Ketebalan kolagen matriks ekstraseluler sel β pankreas dinilai dengan pewarnaan Verhoeff's van Gieson (VvG) dengan sistem skoring. Hasil penelitian menunjukkan ketebalan kolagen matriks ekstraseluler pulau Langerhans pankreas tetap normal pada semua kelompok penelitian. Pemberian ALA 60 mg/kgbb selama 3 minggu pada tikus DM tipe 2 tidak memiliki efek terhadap ketebalan kolagen ECM pankreas. Dengan demikian perlu dilakukan penelitian lanjutan mengenai efek ALA terhadap kolagen matriks ekstra seluler pankreas DM tipe 2 tahap lanjut.


Author(s):  
SARIKA KS ◽  
VANDANA BALAKRISHNAN ◽  
HARISH KUMAR ◽  
ANAND KUMAR ◽  
KR SUNDARAM

Objective: This study aims in understanding the effects of Integrated Amrita Meditation (IAM), a type of mindfulness meditation, on the autonomic balance of type 2 diabetic patients through assessment of heart rate variability (HRV). Methods: After the initial screening of 30 type 2 diabetic subjects, 10 type 2 diabetic subjects between the age group of 30 and 65 years were randomized into two groups, diabetic test (n=5) and diabetic control group (n=5). Diabetic test group practiced IAM technique under the guidance of a trained practitioner. Both the groups continued the same dietary pattern and medications during the 6-month study period. HRV was taken for all subjects at baseline and after 6 months. In our study, we have focused on the power spectral analysis of HRV which include normalized units of high frequency (nHF), low frequency (nLF), and low frequency-high frequency ratio (LF/HF ratio). Results: Mean percentage change in nHF, nLF, and LFHF ratio showed significant changes in between-group comparison (p<0.05). Normalized units of HF increased (p=0.049) while LF (p=0.036) and LFHF ratio (p=0.024) decreased significantly within test group after 6 months of IAM practice suggesting the potential of IAM in improving the parasympathetic tone, thereby tuning the mind and body to calm down during stress. Conclusion: Our study has shown demonstrable improvement in autonomic function which reflects reduced stress after the practice of IAM in diabetic patients.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Lishan Zhou ◽  
Hui Dong ◽  
Yi Huang ◽  
Lijun Xu ◽  
Xin Zou ◽  
...  

Hu-Lu-Ba-Wan (HLBW) is a Chinese herbal prescription used to treat kidney deficiency. The aim of this study was to explore the effect and mechanism of HLBW on diabetic nephropathy (DN) in type 2 diabetic rats. The rat model of DN was established by being fed a high-fat diet and intravenous injection of streptozotocin. Then, HLBW decoction was administered for 16 weeks. Blood glucose level, lipid profile, renal function, 24-hour total urinary protein, and albumin content were examined. Renal morphology and superoxide anion levels were evaluated. The activity of nicotinamide-adenine dinucleotide phosphate (NADPH) and protein kinase C-alpha (PKC-α) related genes expression in renal tissue were also determined. Our data demonstrated that HLBW significantly improved hyperglycemia, hyperlipidemia, and proteinuria in diabetic rats compared with those of control group. HLBW also alleviated glomerular expansion and fibrosis, extracellular matrix accumulation and effacement of the foot processes. Additionally, HLBW reduced superoxide anion level, NADPH oxidase activity, the protein and mRNA expressions of p47phox, and the protein expression of phosphorylated PKC-αin renal tissue. These results suggest that HLBW is effective in the treatment of DN in rats. The underlying mechanism may be related to the attenuation of renal oxidative stress via PKC-α/NADPH oxidase signaling pathway.


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