Poly(ADP-ribose) polymerase-1 (PARP-1) gene deficiency alleviates diabetic kidney disease

AbstractPoly(ADP-ribose)polymerase (PARP) inhibitors prevent or alleviate diabetic nephropathy. This study evaluated the role for PARP-1 in diabetic kidney disease using the PARP-1-deficient mouse. PARP-1−/− and the wild-type (129S1/SvImJ) mice were made diabetic with streptozotocin, and were maintained for 12weeks. Final blood glucose concentrations were increased ∼3.7-fold in both diabetic groups. PARP-1 protein expression (Western blot analysis) in the renal cortex was similar in non-diabetic and diabetic wild-type mice (100% and 107%) whereas all knockouts were PARP-1-negative. PARP-1 gene deficiency reduced urinary albumin (ELISA) and protein excretion prevented diabetes-induced kidney hypertrophy, and decreased mesangial expansion and collagen deposition (both assessed by histochemistry) as well as fibronectin expression. Renal podocyte loss (immunohistochemistry) and nitrotyrosine and transforming growth factor-β1 accumulations (both by ELISA) were slightly lower in diabetic PARP-1−/− mice, but the differences with diabetic wild-type group did not achieve statistical significance. In conclusion, PARP-1−/− gene deficiency alleviates although does not completely prevent diabetic kidney disease

High-Fat Diet-Induced Neuropathy of Prediabetes and Obesity: Effect of PMI-5011, an Ethanolic Extract of Artemisia dracunculus L.

Artemisia species are a rich source of herbal remedies with antioxidant and anti-inflammatory properties. We evaluated PMI-5011, an ethanolic extract of Artemisia dracunculus L., on neuropathy in high-sfat diet-fed mice, a model of prediabetes and obesity developing oxidative stress and proinflammatory changes in peripheral nervous system. C57Bl6/J mice fed high-fat diet for 16 weeks developed obesity, moderate nonfasting hyperglycemia, nerve conduction deficit, thermal and mechanical hypoalgesia, and tactile allodynia. They displayed 12/15-lipoxygenase overexpression, 12(S)-hydroxyeicosatetraenoic acid accumulation, and nitrosative stress in peripheral nerve and spinal cord. PMI-5011 (500 mgkg−1d−1, 7 weeks) normalized glycemia, alleviated nerve conduction slowing and sensory neuropathy, and reduced 12/15-lipoxygenase upregulation and nitrated protein expression in peripheral nervous system. PMI-5011, a safe and nontoxic botanical extract, may find use in treatment of neuropathic changes at the earliest stage of disease

Evaluation of α1‐adrenoceptor antagonist on diabetes‐induced changes in peripheral nerve function, metabolism, and antioxidative defense

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154412/1/fsb2fj990803com.pd

An aldose reductase inhibitor reverses early diabetes‐induced changes in peripheral nerve function, metabolism, and antioxidative defense

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154366/1/fsb2fj010603fje-sup-0001.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154366/2/fsb2fj010603fje.pd

Cannabidiol attenuates high glucose-induced endothelial cell inflammatory response and barrier disruption.

A nonpsychoactive cannabinoid cannabidiol (CBD) has been shown to exert potent anti-inflammatory and antioxidant effects and has recently been reported to lower the incidence of diabetes in nonobese diabetic mice and to preserve the blood-retinal barrier in experimental diabetes. In this study we have investigated the effects of CBD on high glucose (HG)-induced, mitochondrial superoxide generation, NF-kappaB activation, nitrotyrosine formation, inducible nitric oxide synthase (iNOS) and adhesion molecules ICAM-1 and VCAM-1 expression, monocyte-endothelial adhesion, transendothelial migration of monocytes, and disruption of endothelial barrier function in human coronary artery endothelial cells (HCAECs). HG markedly increased mitochondrial superoxide generation (measured by flow cytometry using MitoSOX), NF-kappaB activation, nitrotyrosine formation, upregulation of iNOS and adhesion molecules ICAM-1 and VCAM-1, transendothelial migration of monocytes, and monocyte-endothelial adhesion in HCAECs. HG also decreased endothelial barrier function measured by increased permeability and diminished expression of vascular endothelial cadherin in HCAECs. Remarkably, all the above mentioned effects of HG were attenuated by CBD pretreatment. Since a disruption of the endothelial function and integrity by HG is a crucial early event underlying the development of various diabetic complications, our results suggest that CBD, which has recently been approved for the treatment of inflammation, pain, and spasticity associated with multiple sclerosis in humans, may have significant therapeutic benefits against diabetic complications and atherosclerosis

Aldose Reductase Inhibitor Ameliorates Renal Vascular Endothelial Growth Factor Expression in Streptozotocin-Induced Diabetic Rats

PURPOSE: The vascular endothelial growth factor (VEGF) expression of podocyte is one of the well-known major factors in development of diabetic nephropathy. In this study, we investigated the effects of aldose reductase inhibitor, fidarestat on diabetic nephropathy, and renal VEGF expression in a type 1 diabetic rat model. MATERIALS AND METHODS: Twenty four Sprague-Dawley male rats which were performed intraperitoneal injection of streptozotocin and normal six rats were divided into four groups including a normal control group, untreated diabetic control group, aldose reductase (AR) inhibitor (fidarestat, 16 mg kg(-1) day(-1)) treated diabetic group, and angiotensin receptor blocker (losartan, 20 mg kg(-1) day(-1)) treated diabetic group. We checked body weights and blood glucose levels monthly and measured urine albumin-creatinine ratio (ACR) at 8 and 32 weeks. We extracted the kidney to examine the renal morphology and VEGF expressions. RESULTS: The ACR decreased in fidarestat and losartan treated diabetic rat groups than in untreated diabetic group (24.79 +/- 11.12, 16.11 +/- 9.95, and 84.85 +/- 91.19, p < 0.05). The renal VEGF messenger RNA (mRNA) and protein expression were significantly decreased in the fidarestat and losartan treated diabetic rat groups than in the diabetic control group. CONCLUSION: We suggested that aldose reductase inhibitor may have preventive effect on diabetic nephropathy by reducing renal VEGF overexpression.ope

Red Cabbage (Brassica oleracea) Ameliorates Diabetic Nephropathy in Rats

The protective action against oxidative stress of red cabbage (Brassica oleracea) extract was investigated. Diabetes was induced in male Wistar rats using streptozotocin (60 mg/kg body weight). Throughout the experimental period (60 days), diabetic rats exhibited many symptoms including loss of body weight, hyperglycemia, polyuria, polydipsia, renal enlargement and renal dysfunction. Significant increase in malondialdehyde, a lipid peroxidation marker, was observed in diabetic kidney. This was accompanied by a significant increase in reduced glutathione and superoxide dismutase activity and a decrease in catalase activity and in the total antioxidant capacity of the kidneys. Daily oral ingestion (1 g/kg body weight) of B. oleracea extract for 60 days reversed the adverse effect of diabetes in rats. B. oleracea extract lowered blood glucose levels and restored renal function and body weight loss. In addition, B. oleracea extract attenuated the adverse effect of diabetes on malondialdehyde, glutathione and superoxide dismutase activity as well as catalase activity and total antioxidant capacity of diabetic kidneys. In conclusion, the antioxidant and antihyperglycemic properties of B. oleracea extract may offer a potential therapeutic source for the treatment of diabetes

Bone Marrow-Derived Mesenchymal Stem Cells Improve the Functioning of Neurotrophic Factors in a Mouse Model of Diabetic Neuropathy

Diabetic neuropathy is one of the most frequent and troublesome complications of diabetes. Although there has been a continuous increase in the incidence of diabetic neuropathy, treatments have yet to be found that effectively treat diabetic neuropathy. Neurotrophic factors are proteins that promote the survival of specific neuronal populations. They also play key roles in the regeneration of peripheral nervous system. Recent evidence from diabetic animal models and human diabetic subjects suggest that reduced availability of neurotrophic factors may contribute to the pathogenesis of diabetic neuropathy. One way to reverse this effect is to take advantage of the finding that bone marrow derived mesenchymal stem cells (BM-MSCs) promote peripheral nerve repair and the functioning of neurotrophic factors. Therefore, we speculated that treatment with BM-MSCs could be a viable therapeutic strategy for diabetic neuropathy. The present study was designed to examine the possible beneficial effect of BM-MSCs on functions of neurotrophic factors in diabetic neuropathy. To assess this possibility, we used an in vivo streptozotocin-induced diabetic neuropathy mouse model. Quantitative real-time polymerase-chain reacion showed that BM-MSCs significantly increase expression levels of neurotrophic factors. Also, BM-MSCs ameliorated nerve conduction velocity in streptozotocin-treated mice. These results may help to elucidate the mechanism by which BM-MSCs function as a cell therapy agent in diabetic neuropathy

Alterations in the blood glucose, serum lipids and renal oxidative stress in diabetic rats by supplementation of onion (Allium cepa. Linn)

This study examined the anti-diabetic effect of onion (Allium cepa. Linn) in the streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats were divided into normal rats fed control diet or supplemented with onion powder (7% w/w) and diabetic rats fed control diet or supplemented with onion powder. Diabetes was induced by a single injection of STZ (60 mg/kg, ip) in citrate buffer. The animals were fed each of the experimental diet for 5 weeks. Blood glucose levels of rats supplemented with onion were lower than those of rats fed control diet in the diabetic rats. Onion also decreased the total serum lipid, triglyceride, and atherogenic index and increased HDL-cholesterol/total cholesterol ratio in the diabetic rats. Glutathione peroxidase, glutathione reductase and glutathione S-transferase activities were high in the diabetic rats compared to normal rats and reverted to near-control values by onion. These results indicate that onion decreased blood glucose, serum lipid levels and reduced renal oxidative stress in STZ-induced diabetic rats and this effect might exert the anti-diabetic effect of onion