Deysi Y. Bermúdez-Ocaña

Hypoglycemic effect of Carica papaya leaves in streptozotocin-induced diabetic rats

BackgroundTraditional plant treatment for diabetes has shown a surging interest in the last few decades. Therefore, the purpose of this study was to assess the hypoglycemic effect of the aqueous extract of C. papaya leaves in diabetic rats. Several studies have reported that some parts of the C. papaya plant exert hypoglycemic effects in both animals and humans.MethodsDiabetes was induced in rats by intraperitoneal administration of 60 mg/kg of streptozotocin (STZ). The aqueous extract of C. papaya was administered in three different doses (0.75, 1.5 and 3 g/100 mL) as drinking water to both diabetic and non-diabetic animals during 4 weeks.ResultsThe aqueous extract of Carica papaya (0.75 g and 1.5 g/100 mL) significantly decreased blood glucose levels (p<0.05) in diabetic rats. It also decreased cholesterol, triacylglycerol and amino-transferases blood levels. Low plasma insulin levels did not change after treatment in diabetic rats, but they significantly increased in non-diabetic animals. Pancreatic islet cells were normal in non-diabetic treated animals, whereas in diabetic treated rats, C. papaya could help islet regeneration manifested as preservation of cell size. In the liver of diabetic treated rats, C. papaya prevented hepatocyte disruption, as well as accumulation of glycogen and lipids. Finally, an antioxidant effect of C. papaya extract was also detected in diabetic rats.ConclusionsThis study showed that the aqueous extract of C. papaya exerted a hypoglycemic and antioxidant effect; it also improved the lipid profile in diabetic rats. In addition, the leaf extract positively affected integrity and function of both liver and pancreas.

Prevalence of Anxiety and Depression among Outpatients with Type 2 Diabetes in the Mexican Population

Background Depression and anxiety are common in diabetic patients; however, in recent years the frequency of these symptoms has markedly increased worldwide. Therefore, it is necessary to establish the frequency and factors associated with depression and anxiety, since they can be responsible for premature morbidity, mortality, risk of developing comorbidities, complications, suffering of patients, as well as escalation of costs. We studied the frequency of depression and anxiety in Mexican outpatients with type 2 diabetes and identified the risk factors for depression and anxiety. Methods and Findings We performed a study in 820 patients with type 2 diabetes. The prevalence of depression and anxiety was estimated using the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale, respectively. We calculated the proportions for depression and anxiety and, after adjusting for confounding variables, we performed multivariate analysis using multiple logistic regressions to evaluate the combined effect of the various factors associated with anxiety and depression among persons with type 2 diabetes. The rates for depression and anxiety were 48.27% (95% CI: 44.48–52.06) and 55.10% (95% CI: 51.44–58.93), respectively. Occupation and complications in diabetes were the factors associated with anxiety, whereas glucose level and complications in diabetes were associated with depression. Complications in diabetes was a factor common to depression and anxiety (p<0.0001; OR 1.79, 95% CI 1.29–2.4). Conclusions Our findings demonstrate that a large proportion of diabetic patients present depression and/or anxiety. We also identified a significant association between complications in diabetes with depression and anxiety. Interventions are necessary to hinder the appearance of complications in diabetes and in consequence prevent depression and anxiety.

Spinal nerve ligation reduces nitric oxide synthase activity and expression: Effect of resveratrol

The effect of resveratrol on activity and expression of nitric oxide synthase (NOS) in the spinal cord of neuropathic rats was assessed. Spinal nerve ligation produced tactile allodynia along with a reduction of catalytic activity of the constitutive Ca(2+)-dependent NOS (eNOS and nNOS isoforms) in the ipsilateral dorsal horn, but not contralateral dorsal or ipsilateral or contralateral ventral, spinal cord at 1, 5, 10 and 15 days after surgery compared to naïve and sham-operated animals. Nerve ligation also induced a reduction of nNOS expression in the ipsilateral dorsal horn spinal cord at 10 and 15 days after surgery. Intrathecal resveratrol reduced allodynia and reversed the reduction of constitutive Ca(2+)-dependent NOS activity in the ipsilateral dorsal spinal cord. Moreover, resveratrol significantly reversed the reduction of nNOS expression in the ipsilateral dorsal horn spinal cord. Results show that spinal nerve ligation leads to development of tactile allodynia along with a reduction in constitutive Ca(2+)-dependent NOS activity and nNOS isoform expression in the ipsilateral dorsal horn. Data suggest that resveratrol may reduce tactile allodynia in neuropathic rats by restoring altered NOS activity and expression.

Proglumide enhances the antinociceptive effect of cyclooxygenase inhibitors in diabetic rats in the formalin test

The purpose of this study was to assess the effect of the non-selective cholecystokinin receptor antagonist proglumide on the antinociceptive activity of ketorolac and meloxicam in non-diabetic and diabetic rats. Streptozotocin (60 mg/kg) injection caused hyperglycemia which was maintained for 2 weeks. Formalin-evoked flinching was increased in diabetic rats as compared to non-diabetic rats. Local peripheral ipsilateral, but not contralateral, administration of ketorolac and meloxicam produced antinociception in non-diabetic and diabetic rats. However, the antinociceptive effect of both drugs was significantly reduced in diabetic animals. Proglumide was ineffective by itself and it did not affect the antinociception induced by the cyclooxygenase inhibitors in non-diabetic rats. Contrariwise, proglumide reduced formalin-induced nociception and it increased ketorolac- or meloxicam-induced antinociception in diabetic rats. These results suggest that peripheral cholecystokinin plays an important role in diabetes-induced sensitization as well as in the reduction of the antinociceptive effects of ketorolac and meloxicam in diabetic rats. The combination of cholecystokinin receptor antagonists and ketorolac or meloxicam may be a useful strategy to reduce nociception in diabetic patients.

Isobolographic Analyses of Proglumide–Celecoxib Interaction in Rats with Painful Diabetic Neuropathy

Preclinical Research

Erythropoietin: A potential drug in the management of diabetic neuropathy

Erythropoietin (EPO) is required for promoting the progress of erythroid differentiation. However, the discovery of EPO and the EPO receptor (EPOR) in the nervous system may contribute to new treatment strategies for the use of EPO in neurodegenerative disorders. Diabetic neuropathy is a neurodegenerative disease that affects a large proportion of diabetic patients and results in alterations in functionality, mood and sleep. The pathogenic mechanisms generating diabetic neuropathy involve: Schwannopathy, polyol pathway activity, advanced glycation end-products (AGEs) accumulation, protein kinase C (PKC) activity, increased hexosamine pathway flux, oxidative stress, nitric oxide and inflammation. In this sense, evidence from both clinical and experimental studies indicates that EPO may reverse diabetic neuropathy through an antioxidant action by decreasing pro-inflammatory cytokines, restoring Na+/K+-ATPase activity, and blocking the generation of pro-apoptotic proteins. The aim of this review is to discuss the neuroprotector effect of EPO on pathogenic mechanisms of diabetic neuropathy.