scholarly journals Cholesterol Contributes to Diabetic Nephropathy through SCAP-SREBP-2 Pathway

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Hong Sun ◽  
Yang Yuan ◽  
Zi-Lin Sun

Diabetic nephropathy (DN) has been associated with the presence of lipid deposition. We hypothesized that the disruption of intracellular cholesterol feedback may contribute to DN. Diabetes was induced by high fat/sucrose diet and low-dose intraperitoneal injection of streptozocin (STZ) in male Sprague-Dawley rats. Then diabetic rats were randomly divided into two groups: untreated diabetic group (DM) and atorvastatin-treated group (DM + AT). We found that the levels of serum blood urea nitrogen and creatinine, as well as 24-hour urine protein and urinary neutrophil gelatinase-associated lipocalin, were significantly increased in diabetic rats. This result indicated that the diabetic rats suffered from functional renal damage. We also observed lipid droplet accumulation and increase in 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR), low density lipoprotein receptor (LDLr), sterol regulatory element binding protein-2 (SREBP-2), and SREBP-cleavage activating protein (SCAP) in the kidneys of diabetic rats. However, atorvastatin ameliorated renal lipid accumulation and improved the renal function of diabetic rats despite an increase in mRNA and protein expressions of HMG-CoAR, LDLr, and SREBP-2. These results demonstrated that intracellular cholesterol feedback regulation is disrupted in rats with type 2 diabetes, thereby causing renal cholesterol accumulation. Atorvastatin ameliorated renal cholesterol accumulation by reducing renal cholesterol synthesis.

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Ochuko L. Erukainure ◽  
Osaretin A. T. Ebuehi ◽  
Folasade O. Adeboyejo ◽  
Olufunmilola O. Oladunmoye ◽  
Muhammad Aliyu ◽  
...  

The effects of fibre-enriched biscuit on biomarkers associated with hepatotoxicity in diabetic rats were investigated. Diabetes was induced by single intraperitoneal injection of alloxan monohydrate. Treatment lasted for 14 days after which the rats were sacrificed by cervical dislocation. Blood serum was analyzed to determine hepatic function enzymes. The liver was also analyzed to determine hepatic lipid profile and antioxidant enzymes. Induction of diabetes led to elevated levels of ALP, AST, and ALT. These were, however, significantly (p<0.05) reduced in the fibre-enriched biscuit fed (treated) group. There was no significant difference in the serum bilirubin and total protein levels of the studied groups. Reduced albumin level was observed in the diabetic group; this was further lowered on feeding with fibre-enriched biscuits. Induction of diabetes led to increased hepatic level of cholesterol, triglyceride (TG), low density lipoprotein (LDL), and lipid peroxidation and decreased activities of glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) and HDL level. These were significantly (p<0.05) reversed on feeding with fibre-enriched biscuit. This study portrays the protective effect of fibre-enriched biscuit on increased oxidative stress and hyperlipidemia in hepatic tissues of alloxan-induced diabetic rats.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1048
Author(s):  
Noha M. Meligi ◽  
Amro K.F. Dyab ◽  
Vesselin N. Paunov

We developed a dual microencapsulation platform for the type 2 diabetes drug metformin (MTF), which is aimed to increase its bioavailability. We report the use of Lycopodium clavatum sporopollenin (LCS), derived from their natural spores, and raw Phoenix dactylifera L. (date palm) pollens (DPP) for MTF microencapsulation. MTF was loaded into LCS and DPP via a vacuum and a novel method of hydration-induced swelling. The loading capacity (LC) and encapsulation efficiency (EE) percentages for MTF-loaded LCS and MTF-loaded DPP microcapsules were 14.9% ± 0.7, 29.8 ± 0.8, and 15.2% ± 0.7, 30.3 ± 1.0, respectively. The release of MTF from MTF-loaded LCS microcapsules was additionally controlled by re-encapsulating the loaded microcapsules into calcium alginate (ALG) microbeads via ionotropic gelation, where the release of MTF was found to be significantly slower and pH-dependent. The pharmacokinetic parameters, obtained from the in vivo study, revealed that the relative bioavailability of the MTF-loaded LCS-ALG beads was 1.215 times higher compared to pure MTF, following oral administration of a single dose equivalent to 25 mg/kg body weight MTF to streptozotocin (STZ)-induced diabetic male Sprague-Dawley rats. Significant hypoglycemic effect was obtained for STZ-induced diabetic rats orally treated with MTF-loaded LCS-ALG beads compared to control diabetic rats. Over a period of 29 days, the STZ-induced diabetic rats treated with MTF-loaded LCS-ALG beads showed a decrease in the aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglycerides, cholesterol, and low-density lipoprotein-cholesterol (LDL-C) levels, as well as an increase in glutathione peroxidase (GPx) and a recovery in the oxidative stress biomarker, lipid peroxidation (LPx). In addition, histopathological studies of liver, pancreas, kidney, and testes suggested that MTF-loaded LCS-ALG beads improved the degenerative changes in organs of diabetic rats. The LCS-ALG platform for dual encapsulation of MTF achieved sustained MTF delivery and enhancement of bioavailability, as well as the improved biochemical and histopathological characteristics in in vivo studies, opening many other intriguing applications in sustained drug delivery.


2019 ◽  
Vol 9 (4-A) ◽  
pp. 126-136 ◽  
Author(s):  
Karunanithi Kalaivani ◽  
Chandrasekaran Sankaranarayanan

The present study investigates the effect of isopulegol on adipokine secretion and dyslipidemia in high fat diet and streptozotocin (HFD/STZ) induced diabetic rats. Animals were made diabetic by feeding HFD for 4 wks followed by single intraperitoneal injection of STZ (35mg/kg b.w; 0.1M citrate buffer; pH 4.0). Diabetic rats showed increased levels of total cholesterol, triglycerides, free fatty acids, phospholipids, low density lipoprotein-C (LDL-C), very low density lipoprotein -C (VLDL-C) and decreased high density lipoprotein-C levels (HDL-C). Similarly, the activity of HMG-CoA reductase, was increased while lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT) activities were significantly decreased. Furthermore, the expression of sterol regulatory element binding protein-1C (SREBP-1C), adiponectin, peroxisome proliferator activated receptor gamma (PPARγ) were significantly down regulated, whereas leptin expression was upregulated in diabetic rats. Administration of isopulegol (100 mg/kg b.w) for 28 days significantly restored lipid levels in plasma and liver tissue by modulating adipokine secretion in diabetic treated rats. From this we conclude that isopulegol exhibited significant antihyperlipidemic effect in HFD/STZ induced diabetic rats. Keywords: Dyslipidemia, Diabetes mellitus, Adiponectin, Leptin, PPARγ, SREBP-1C


2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Shou-Chieh Wang ◽  
Shiow-Fen Lee ◽  
Chau-Jong Wang ◽  
Chao-Hsin Lee ◽  
Wen-Chin Lee ◽  
...  

Several studies point out that oxidative stress maybe a major culprit in diabetic nephropathy. Aqueous extract ofHibiscus sabdariffaL. (HSE) has been demonstrated as having beneficial effects on anti-oxidation and lipid-lowering in experimental studies. This study aimed at investigating the effects ofHibiscus sabdariffaL. on diabetic nephropathy in streptozotocin induced type 1 diabetic rats. Our results show that HSE is capable of reducing lipid peroxidation, increasing catalase and glutathione activities significantly in diabetic kidney, and decreasing the plasma levels of triglyceride, low-density lipoprotein (LDL) and increasing high-density lipoprotein (HDL) value. In histological examination, HSE improves hyperglycemia-caused osmotic diuresis in renal proximal convoluted tubules (defined as hydropic change) in diabetic rats. The study also reveals that up-regulation of Akt/Bad/14-3-3γand NF-κB-mediated transcription might be involved. In conclusion, our results show that HSE possesses the potential effects to ameliorate diabetic nephropathy via improving oxidative status and regulating Akt/Bad/14-3-3γsignaling.


Author(s):  
Ayoub Amssayef ◽  
Bouchra Azzaou ◽  
Mohammed Ajebli ◽  
Mohamed Eddouks

Aims: The study aimed to evaluate the antihyperlipidemic and antioxidant activities of Matricaria pubescens. Background: Matricaria pubescens (Desf.) Shultz belongs to Asteraceae family and it is commonly used traditionally for handling diabetes mellitus. Objective: The objective of this study was to assess the antioxidant activity of Matricaria pubescens (Desf.) Shultz and its effect on lipid and lipoprotein profile in normal and streptozotocin-induced diabetic rats. Methods: The effect of repeated (7 days of treatment) oral administration of the aqueous extract of aerial part of Matricaria pubescens (MPAE) at a dose of 40 mg/kg on lipid and lipoprotein profile was examined in normal and streptozotocin-induced diabetic rats. Furthermore, a preliminary phytochemical screening and the quantification of phenolic, flavonoid and tannin contents as well as the antioxidant activity using two methods (FRAP and ABTS) were carried out. Results: MPAE demonstrated a potent antidyslipidemic effect in diabetic rats by reducing serum levels of triglycerides, total cholesterol and low-density lipoprotein (LDL). In addition, the results showed that the extract is rich in several phytochemical compounds and revealed an important antioxidant activity. Conclusion: In summary, this study proved that Matricaria pubescens (Desf.) Shultz. has a favorable effect on diabetic dyslipidemia.


2019 ◽  
Vol 8 (6) ◽  
pp. 964-971 ◽  
Author(s):  
Songling Jiang ◽  
Do Van Quan ◽  
Jae Hyuck Sung ◽  
Moo-Yeol Lee ◽  
Hunjoo Ha

Abstract Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease. Epidemiological studies have demonstrated that cigarette smoke or nicotine is a risk factor for the progression of chronic kidney injury. The present study analyzed the kidney toxicity of cigarette smoke in experimental rats with DKD. Experimental diabetes was induced in 7-week-old Sprague-Dawley rats by a single intraperitoneal injection of streptozotocin (60 mg kg−1). Four weeks after the induction of diabetes, rats were exposed to cigarette smoke (200 μg L−1), 4 h daily, and 5 days per week for 4 weeks. Cigarette smoke did not affect the levels of plasma glucose, hemoglobin A1c, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol or non-esterified fatty acids in both control and diabetic rats under the experimental conditions. Cigarette smoke, however, significantly increased diabetes-induced glomerular hypertrophy and urinary kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) excretion, suggesting exacerbation of diabetic kidney injury. Cigarette smoke promoted macrophage infiltration and fibrosis in the diabetic kidney. As expected, cigarette smoke increased oxidative stress in both control and diabetic rats. These data demonstrated that four weeks of exposure to cigarette smoke aggravated the progression of DKD in rats.


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