Alloxan-treated Rats Research Articles

Berberine hydrochloride-loaded lipid-based nanoparticles ameliorate β-cell function by targeting Nrf2/NF-κB signaling pathway in alloxan-induced diabetes using a murine model: Optimization through full factorial design

Berberine hydrochloride (BH), a naturally occurring alkaloid having pleiotropic biological effects, is characterized by high water solubility, poor bioavailability, and a brief half-life. The objective of this study was to develop a liposomal formulation of BH that is more accessible and to ascertain whether its intraperitoneal administration might mitigate pancreatic tissue damage in rats that have been induced by alloxan. Rats were divided into four groups: control, alloxan, metformin, and BH-liposomes (BH-Lip). Measurements of blood glucose, insulin, pancreatic antioxidant state, and pro-inflammatory mediators were used to assess the severity of pancreatic injury in rats among all groups. According to the results, BH-Lip reduced the extent of alloxan-induced pancreatic tissue damage in rats, as demonstrated by improved HOMA-IR and HOMA-β scores, insulin, total pancreatic antioxidant capacity, and lower blood glucose levels. Furthermore, BH-Lip boosted the antioxidant transcription factor Nrf2 and downregulated the mRNA expression of pancreatic pro-inflammatory mediators, such as NF-κB and NLRP3. Moreover, immuno-histochemical labeling revealed that BH-Lip inhibited the protein transcription of caspase-3 and TNF-α in the pancreatic tissues of alloxan-treated rats. These findings provide BH-Lip as a safe substitute for traditional antidiabetics by reducing pancreatic tissue damage caused by alloxan via targeting the Nrf2/NF-κB pathway.

Symbiotic Antidiabetic Effect of Lactobacillus casei and the Bioactive Extract of Cleome droserifolia (Forssk.) Del. on Mice with Type 2 Diabetes Induced by Alloxan.

The consumption of probiotics protects pancreatic β-cells from oxidative damage, delaying the onset of type 2 diabetes mellitus (T2DM) and preventing microvascular and macrovascular complications. This study aimed to evaluate the antidiabetic activity of CDE fermented by Lactobacillus casei (ATCC 39539) (LC) in alloxan-induced diabetic rats. The oxidative stress identified by catalase (CAT), serum AST, ALT, ALP, creatinine, urea, and uric acid were measured. The chemical profiles of the plant extract and the fermented extract were studied using HPLC/MS. The potential of the compounds towards the binding pockets of aldose reductase and PPAR was discovered by molecular docking. A significant reduction in fasting blood glucose in alloxan-treated rats. The CAT showed a significant decrease in diabetic rats. Also, serum AST, ALT, ALP, creatinine, urea, and uric acid were significantly decreased in the mixture group. Mild histological changes of pancreatic and kidney tissues suggested that the mixture of probiotics and cleome possesses a marked anti-diabetic effect. Overall, the study suggests that the combination of Cleome droserifolia fermented by Lactobacillus casei exhibits significant antidiabetic activity (p-value=0.05), reduces oxidative stress, improves lipid profiles, and shows potential for the treatment of diabetes.

Effect of Some Medicinal Plants Extracts and Chemicals on Enzymes and Tissues Liver of Female Rats

The study was carried out on 45 sexually mature female albino rats at the age of 7-8 weeks and weighing 160-180; nine treatments were used in this study, where five rats were isolated for the control treatment (without infection); the remaining rats were injected (Subcutaneous) with Indian-made Alloxan, which was prepared at the time of injection at a dose of 100 mg/kg of body weight. The results showed a significant decrease in liver enzymes AST and the ALP characteristic in T3, T4, T5, T6, T7, T8, and T9, as well as a significant decrease in the ALT characteristic in T3, T5, T6, T7, and T9. Histological effects We notice severe damage to the liver tissue of alloxan-treated rats compared to the proper treatment, represented in the liver tissue by necrosis of liver cells, the presence of a blood clot, the absence of sinusoids, and the thickening of the nuclei. The results have shown that the aqueous extracts positively affect zymes and tissues in female rats.

Evaluation of Hypoglycemic potential of Moringa oleifera bark extracts on normal and Alloxanized diabetic rats

Diabetes Mellitus is a leading community health agony. Although steady new drug evolution to care intended for diabetes, herbal remedy stay a prospective add-on remedy to maintain glucose level in the body. Moringa oleifera (Moringaceae) has been conventionally used to deal with numerous diseases as the anti-oxidant properties it reports. The effect M. oleifera stem bark extracts against diabetes alloxanized diabetic rats were employed in this research. Bark of M. oleifera stem was used. Male Wistar albino rats (150–200g) were employed. Blood samples were accumulated by retro-orbital plexus puncture method and blood glucose of all animals was examined by means of an electronic glucometer. Diabetes commences due to Alloxan during its capability to demolish the insulin-generating beta cells of the pancreas. Three weeks observations indicate drop in blood glucose levels as in Alloxan + glibenclamide (10mg/kg) used as standard from 295mg/dl to 149mg/dl. Alloxan + Methanolic extract of M. oleifera (100mg/kg) from 294 mg/dl to 237mg/dl. Alloxan + Methanolic extract of M. oleifera (200mg/kg) from 295mg/dl to 232mg/dl. Alloxan + Methanolic extract of M. oleifera (400 mg/kg) from 290mg/dl to 229mg/dl. Three weeks of daily treatment of extract of M. oleifera led to a dose dependent fall in blood sugar in three weeks for methanolic extract of M. oleifera. The current research concludes that extracts of M. oleifera bark is able to demonstrate drop in blood glucose level in normal and alloxan treated rats.

Responsivity of lateral septum-mPFC connections in alloxan-induced hyperglycemia

The lateral septal nucleus (LSN) is related to the actions of antidepressants, and the prelimbic cortex (PL) and infralimbic cortex (IL) modulate responses to fear. However, unknown is whether experimental diabetes that is induced by alloxan alters the responsivity of these regions. We used a method in which one forebrain region (LSN) was electrically stimulated while single-unit extracellular recordings were performed in another mPFC region (PL and IL). Several experimental groups were tested: (a) animals that were subjected to long-term (42-day) alloxan-hyperglycemia and protected with insulin, (b) healthy animals that received a low dose of insulin that does not produce changes in glycemia, and (c) animals that received long-term treatment with fluoxetine. Additional healthy groups of animals received insulin or fluoxetine and underwent the forced swim test. Biological measurements indicated the induction of diabetes in alloxan-treated rats. In this group, a shift toward an inhibitory response to LSN stimulation was observed in the PL and IL compared with the control group. A low dose of insulin or fluoxetine produced similar changes in LSN-PL and LSN-IL responsivity. Long-term hyperglycemia increased inhibitory responsivity in the LSN-PL and LSN-IL, but this action was less pronounced than the action that was exerted by insulin and fluoxetine, which produced similar actions. Such similar actions were confirmed in the forced swim test, in which the antidepressant-like effects of insulin partially resembled the effects of fluoxetine. The changes that were observed in the alloxan group appeared to be related to neuronal damage, and a low dose of insulin exerted some antidepressant-like actions.

Partial recovery from alloxan-induced diabetes by sodium phthalhydrazide in rats

In the commonly used experimental model of diabetes, a cytotoxic glucose analogue alloxan can selectively destruct pancreatic β-cells, with characteristics similar to the type-1 diabetes (T1D) in humans. Treatment of diabetic rats with sodium phthalhydrazide partially reversed diabetogenic pathology in the alloxan-induced diabetes. The alloxan-treated rats with permanent hyperglycemia, which further received i.p. twenty daily doses 2mg/kg b.w. phthalhydrazide, showed at 60days of the experiment a significant amelioration of the diabetes status. Hyperglycemia was decreased by 52%, glycated haemoglobin HbA1c returned to control value, insulin concentration significantly increased from 45,4% (alloxan group) to 59,5% (alloxan+phthalhydrazide) of the control values. Importantly, phthalhydrazide treatment of alloxan-treated diabetic rats markedly decreased the concentrationof interleukin-6 (IL-6) and corticosterone level. Morphometric analysis revealed a marked increase in the number of pancreatic islets/mm2, and a number of cells/mm2 in the pancreatic islets. These changes, including 3-fold increase in the number of insulin-producing cells and 2-fold decrease in blood glucose levels, correlated with the increased proliferative activity of pancreatic β-cells in the diabetic phthalhydrazide-treated animals. Interestingly, the number of CD68+ cells/macrophages in the pancreatic islets, which was relatively high in the alloxan group (63,9+− 16.4/mm2), markedly decreased after the phthalhydrazide treatment (23,6+−7,2/mm2). Taking together with the previous data on the phthalhydrazide-related macrophage silencing, restriction of macrophage quantity in the alloxan-affected pancreatic islets can be possibly one of important events leading to the partial recovery from the β-cell disruption.

Anti-Hyperglycaemic Effect of Cleome Rutidosperma in Alloxan-Induced Diabetic Albino Rats.

The hypoglycaemic and antihyperglycaemic effects of methanol extract of leaves of Cleome rutidosperma (Cr) DC (Family: Capparidaceae) was investigated in Wistar rats. Fifty normoglycaemic male rats (120 g-200 g) were divided into groups A (hypoglycaemic study; n=20) and B (antihyperglycaemic study; n=30). Each experiment had one control group and three groups administered with Cr (100, 200 or 400 mg/kg) respectively. Group B had two additional groups of diabetic-untreated rats and glibenclamide-treated diabetic rats. Diabetes was induced in Group B rats (except control) fasted overnight for 12 h by intraperitoneal injection of Alloxan (100 mg/kg). Fasting blood glucose levels (FBGL) were determined and alloxan-treated rats with BGL >200 mg/dl 48 h post-induction were considered diabetic. Data obtained were analyzed using One-way ANOVA and Duncan Multiple Range Test (p<0.05). Cr-treated rats showed significant decline in BGL with noteworthy decline by day 3 post-treatment at the dose of 200 mg/kg (236.40±14.72 mg/dl) from 336.40±21.06 mg/dl. Cr at the dose of 200 mg/kg (72.20±6.18 mg/dl, 69.20±7.81 mg/dl, 137.80±7.15 mg/dl and 70.60±10.66 mg/dl) showed better glycemic control compared to glibenclamide (194.50±7.75 mg/dl, 253.75±7.20 mg/dl, 284.25±10.56 mg/dl and 156.00±10.80 mg/dl). Cr-treated rats also showed progressive weight gain through the course of the study. This study demonstrated Cr has antihyperglycemic effect with more rapid onset of action and better glycemic control compared to glibenclamide.

English

Diabetes mellitus constitutes a global public health concern and dietary approach is key to the control and prevention of lethal complications. This study investigated the hypoglycemic and anti-hyperglycemic effects of Xanthosoma sagittifolium-incorporated diets in normoglycemic and alloxan-induced diabetic rats. Seventy normoglycemic male Wistar strain albino rats (120 to 200 g) were divided into two groups of thirty-five each. Group 1 was randomly distributed into seven subgroups and each subgroup assigned to 100% rat pellets, X. sagittifolium-incorporated rat pellet (25, 50 and 75%), 100% X. sagittifolium , 100% X. sagittifolium + Glibenclamide (oral hypoglycaemic agent for treatment of diabetes) or 100% rat pellets + Glibenclamide. Diabetes was induced in Group 2 rats fasted for 12 h by intraperitoneal injection of Alloxan (100 mg/kg body weight). Initial fasting blood glucose levels (BGL) were recorded, and alloxan-treated rats with BGL >200 mg/dl 48 h post-induction were considered diabetic and divided into seven subgroups. Dietary treatment was carried out, and blood glucose level (BGL) monitored for 14 days. Data obtained were analyzed using one way analysis of variance (ANOVA) and Tukey’s post-hoc test at p< 0.05. X. sagittifolium caused a significant reduction in the BGL of alloxan-induced diabetic rats (p<0.05) but no hypoglycemic effect in normoglycemic rats. Rats fed 25% (BGL:165.2±16.9 mg/dl), 50% (BGL: 189.2±15.9 mg/dl) and 75% (BGL:152.0±23.0 mg/dl) X. sagittifolium showed better control of BGL by 24 h post-prandial compared with rats administered glibenclamide (BGL: 195.0±18.6 mg/dl) and 100% X. sagittifolium (BGL: 221.0±17.0 mg/dl). Rats fed 75% (BGL: 118.4±11.0 mg/dl) or 100% (BGL: 97.0±17.1 mg/dl) X. sagittifolium had better controlled BGL compared with rats fed pellets and pellets + glibenclamide (BGL: 154.2±19.8 mg/dl) on day 7. X. sagittifolium corm has an antihyperglycemic effect, and its consumption should be encouraged among diabetic patients as a good replacement for other high-calorie diets. Key words: Antihyperglycemic effect, Xanthosoma sagittifolium, diabetes mellitus, albino rat.

HISTOLOGICAL AND BIOMOLECULAR STUDIES OF THE EFFECT OF STEM CELLS THERAPY ON EXPERIMEMTAL PANCREATIC DAMAGE INDUCED BY ALLOXAN IN FEMALE ALBINO RATS

Diabetes mellitus type 1 is an autoimmune disorder that leads to β cell destruction and lowered insulin production. The approach of using stem cells in the clinical field has refocused the objectives of islet transplantation. Accordingly, in the present study experimental rats pancreatic β cells damage was induced using alloxan. Mesenchymal stem cells (MSCs) were separated from bone marrow and differentiated into insulin-producing pancreatic cells. Both undifferentiated mesenchymal stem cells or early differentiated insulin-producing pancreatic cells were injected into the alloxan-treated female albino rats. In addition, alloxan-treated rats were then exposed to 6 Gy γ-radiation prior to cells injection by 24 hours for immunosupression. The rats were monitored for blood glucose levels along the period of the experiment. The results showed that the mean of postprandial blood glucose levels of the diabetic rats with undifferentiated mesenchymal stem cell transplantation or early differentiated insulin-producing pancreatic cells, either exposed to ionizing radiation before cell injection or not, were significantly lower than those of the diabetic rats without cell transplantation. In addition the histological observations showed an amelioration after cell therapy either with or without radiation, as the necrotic cells were just few after 15 days and were absent after 30 days in case of treatment with MSCs. Treatment with early differentiated insulin-producing pancreatic cells after 30 days revealed blood capillary enclosing erythocytes in association with presumably early differentiated pancreatic cells and the migration of these cells into the neighbouring islet tissue. It is concluded that undifferentiated mesenchymal stem cells or early differentiated insulin-producing pancreatic cell therapy have the potential to successfully repair the damage induced by alloxan in rats pancreatic β-cells.

Protective Effect of Abelmoschus esculentus Against Alloxan-induced Diabetes in Wistar Strain Rats

ABSTRACTIncreased oxidative stress has been shown to play an important role in the etiology and pathogenesis of diabetes and its complications. Abelmoschus esculentus (Okra) has been reported to possess many important biological properties. We undertook in vivo studies on male Wistar rats to examine the antioxidative potential of okra in normal and alloxan-treated diabetic rats. Okra extract was administered to control and diabetic rats for 35 consecutive days. Erythrocyte plasma membrane redox system (PMRS) activity (p < 0.05), erythrocytes lipid peroxidation (MDA) (p < 0.01), and advanced oxidation protein products (AOPP) (p < 0.001), increased by 153%, 31%, and 290%, respectively, in response to alloxan treatment, while intracellular reduced glutathione (p < 0.001) and total antioxidant potential of plasma in terms of Ferric reducing ability (FRAP) (p < 0.01) decreased by 75% and 22%, respectively, on alloxan treatment. Okra supplementation provided protection to the rats against alloxan-induced changes. Based on the present results, we hypothesize that okra has strong antioxidative potential and may be used as a dietary supplementation in diabetes for prevention of oxidative stress-mediated complications.

Therapeutic effects of stem cell on hyperglycemia, hyperlipidemia, and oxidative stress in alloxan-treated rats

Diabetes mellitus is the most common endocrine disorder that affects more than 285 million people worldwide. The purpose of this study was to investigate the effect of mesenchymal stem cells (MSCs) from the bone marrow of albino rats, on hyperglycemia, hyperlipidemia, and oxidative stress induced by intraperitoneal injection (i.p.) of alloxan at a dose of 150 mg/kg in rats. Injection of alloxan into rats resulted in a significant increase in serum glucose, total cholesterol, triglyceride, low density lipoprotein cholesterol, and sialic acid level and a significant decrease in serum insulin, high density lipoprotein-cholesterol, vitamin E, and liver glycogen as compared to their corresponding controls. Also, oxidative stress was noticed in pancreatic tissue as evidenced by a significant decrease in glutathione level, superoxide dismutase, glutathione-S-transferase activities, also a significant increase in malondialdehyde and nitric oxide levels when compared to control group. Treatment of diabetic rats with MSCs stem cells significantly prevented these alterations and attenuated alloxan-induced oxidative stress. In conclusion, rat bone marrow harbors cells that have the capacity to differentiate into functional insulin-producing cells capable of controlling hyperglycemia, hyperlipidemia, and oxidative stress in diabetic rats. This may be helpful in the prevention of diabetic complications associated with oxidative stress.

A Study of Prophylactic Effect Against Diabetes of Two Ayurvedic Drugs ‘Jambadyarista’ and ‘Bohumutrantak Ras’ in Normal as well as Alloxan-induced Diabetic Rats

Aims: The present study was designed to evaluate the anti-diabetic as well as prophylactic activity of Jambadyarista and Bohumutrantak Ras in alloxan-induced diabetic rats. Study Design: Study the prophylactic and antiglycemic effects against diabetes of two Ayurvedic drugs ‘Jambadyarista’ and ‘Bohumutrantak Ras’ in normal as well as alloxan-induced diabetic rats using in vivo models. Place and Duration of Study: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Dhaka, Dhaka-1000, Bangladesh between December 2013 and March 2014. Methodology: To investigate the activity, 70 Long Evans rats divided into seven (A-G) groups were included in this study. Diabetes was induced by single intraperitoneal injection of alloxan (150mg/kg body weight) while the Ayurvedic drugs Jambadyarista and Bohumutrantak Ras were given orally at a dose of 200mg/kg of body weight. Group A was control group. Groups B and E were allowed to fast for 12 hours. Diabetes was induced by intraperitoneal injection of freshly prepared solution of alloxan (150mg/kg) in normal saline after base line glucose level determination. The alloxan-treated rats were allowed to food over night to overcome drug induced hyperglycemia. After 48 hours, blood glucose level was measured with an Accu-Chek glucometer using blood sample from the tail vein of each rat. Diabetes was established in animals when blood glucose level was raised to 11.1-32.6mmol/L. After the establishment of diabetes, the experiments were carried out. Groups D and G were allowed to induce diabetes by single intraperitoneal injection of alloxan (75mg/kg body weight) in normal saline every day for 5 days. Results: In case of alloxan-induced diabetic rats, Jambadyarista and Bohumutrantak Ras showed prophylactic activity against diabetes as well as also reduced blood glucose level. By statistical analysis of results, it was found that Jambadyarista and Bohumutrantak Ras have prophylactic activity against diabetes in normal and alloxan- induced diabetic rats. Conclusion: It can be inferred that the Ayurvedic drug “Jambadyarista and Bohumutrantak Ras” significantly possess prophylactic activity against diabetes. They also showed antidiabetic effect in alloxan-induced diabetic rats. Further comprehensive cellular and molecular investigations are required to characterize the exact mechanism responsible for its prophylactic and antidiabetic effects.

Assessment of Alloxan-Induced Diabetic Rats as a Periodontal Disease Model Using a Selective Cyclooxygenase (COX)-2 Inhibitor.

Several recent studies have reported that alloxan-treated rats with long-term hyperglycemia can develop naturally occurring periodontal disease (PD). Our previous studies detected dental caries in the same model. Therefore, these two lesions of different etiologies are expected to occur concurrently. In this study, we evaluated the use of diabetic rats as a PD model by employing a selective COX-2 inhibitor reported to be effective against PD. Six-week-old female F344 rats were divided into 3 groups: intact rats (control), alloxan-induced diabetic rats fed a standard diet (AL) and alloxan-induced diabetic rats fed a diet containing 0.01% etodolac (AL+Et). The animals were euthanized at 26 weeks of age, and their oral tissues were examined histopathologically. Gingivitis, marginal periodontitis and alveolar bone resorption were markedly enhanced along with dental caries in the AL group compared with the control group. However, the COX-2 inhibitor had no effect on periodontal inflammation in the AL+Et group. In addition, in the AL group, periodontitis was notably nonexistent around the normal molars, and gingivitis was scarcely worse than that in the control group. In the diabetic rats, the progression of periodontal inflammation was closely correlated with the severity of adjacent dental caries, and marginal periodontitis was frequently continuous with apical periodontitis. In conclusion, an alloxan-induced diabetic rat is not a model of PD but of dental caries. It is probable that in this model, hyperglycemia may enable crown caries to progress to apical periodontitis, while the associated inflammation may rostrally expand to surrounding periodontal tissue.

Protective effect of Vitamin E (a-tocopherol) on nickel-induced alteration of testicular pathophysiology in alloxan-treated diabetic rats

Background and Aim: Diabetes mellitus is a global problem associated with increased formation of free radicals and decrease in antioxidant potential. Nickel generates free radicals and induces oxidative and nitrosative stress with depletion of antioxidants. Vitamin E is the most effective chain-breaking antioxidant against lipid peroxidation. Therefore, the present study was intended to evaluate the possible protective effect of Vitamin E (α-tocopherol) on oxidative stress in the testis of diabetic rats exposed to nickel. Methods: Diabetes was induced by alloxan monohydrate (15 mg/100 g b.wt, i.p.) in adult male Wistar albino rats. Diabetic rats in respective groups were exposed to nickel sulfate (2.0 mg/100 g b.wt, i.p) and α-tocopherol (10 mg/100 g b.wt, i.m.) alone as well as in combination on alternate days until the tenth doses. Testicular cholesterol and protein, aspartate aminotransferase (AST), alanine aminotransferase (ALT), nitric oxide, and lipid peroxide were evaluated by ultraviolet-visible spectrophotometer. Testicular histopathology was also evaluated. Results: Exposure of diabetes and nickel showed significantly decreased body weight, testicular-somatic index, testicular cholesterol and protein, AST, ALT, nitric oxide, and lipid peroxide levels. Simultaneous α-tocopherol supplementation showed remarkable improvement in all these alterations. We observed damage in testicular architecture with, tortuous seminiferous tubules, foci of congestion, necrosis, loss of spermatogenesis > 75% and loss of germ cell layer in diabetic and nickel-exposed diabetic rats. Testis of simultaneous α-tocopherol supplemented diabetic rats showed many normal seminiferous tubules and normal spermatogenesis (≥50%). Conclusion: Vitamin E (α-tocopherol) supplementation could exert a protective effect on the testis of diabetic rats exposed to nickel by suppressing the increased oxidative stress.

Antidiabetic effect of Sida cordata in alloxan induced diabetic rats.

Medicinal plants are efficient ameliorator of oxidative stress associated with diabetes mellitus. In this study, ethyl acetate fraction (SCEE) of Sida cordata was investigated for scientific validation of its folk use in diabetes. Antidiabetic effect of SCEE was confirmed by antihyperglycemic activity in normal glucose loaded and diabetic glucose loaded animals as well as normal off feed animals. Confirmation of antidiabetic activity and toxicity ameliorative role of S. cordata was investigated in a chronic multiple dose treatment study of fifteen days. A single dose of alloxan (120 mg/kg) produced a decrease in insulin level, hyperglycemia, elevated total lipids, triglycerides, and cholesterol and decreased the high-density lipoproteins. Concurrent with these changes, there was an increase in the concentration of lipid peroxidation (TBARS), H2O2, and nitrite in pancreas, liver, and testis. This oxidative stress was related to a decrease in glutathione content (GSH) and antioxidant enzymes. Administration of SCEE for 15 days after diabetes induction ameliorated hyperglycemia, restored lipid profile, blunted the increase in TBARS, H2O2, and nitrite content, and stimulated the GSH production in the organs of alloxan-treated rats. We suggested that SCEE could be used as antidiabetic component in case of diabetes mellitus. This may be related to its antioxidative properties.

Diabetes mellitus triggers oxidative stress in the liver of alloxan-treated rats: a mechanism for diabetic chronic liver disease

To investigate whether Diabetes mellitus chemically induced by alloxan is capable of changing, in the long term, the oxidative balance in the liver tissue of rats. Sixty male Wistar rats, weighing 250-280 g, were randomly distributed into two experimental groups: NG - 30 non-diabetic control rats; DG - 30 alloxan- induced diabetic rats without any treatment for the disease. Each group was further divided into three subgroups containing ten rats each, which were sacrificed after one, three and six months of follow-up, respectively. Blood glucose, urinary glucose, glycosylated hemoglobin and insulin were determined in the plasma of all animals at the beginning of the experiment and prior to all sacrifice periods. The concentrations of lipid hydroperoxides (HP) and the activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were also measured in the liver tissue of all animals. Rats from the DG group showed high levels of blood glucose, urinary glucose, and glycosylated hemoglobin, with significantly lower plasma insulin levels than those observed in NG rats (p<0.001). Diabetic animals also showed increased concentration of HP free radicals in the liver tissue as compared to those shown by NG animals after one, three and six months of follow-up. In contrast, the antioxidant activity of the enzymes SOD, CAT and GSH-Px was significantly reduced in all follow-up periods (p<0.01). Diabetes determines oxidative stress in the liver, which is characterized by increased concentration of reactive oxygen species (ROS) in tissue and significant reduction in their antioxidant defenses. Such oxidative unbalance in the liver cells may play a relevant role in the genesis of the diabetic chronic liver disease, including the non-alcoholic fatty liver disease and its occasional progression to steatohepatitis and cirrhosis.

Nano-titanium dioxide induced cardiac injury in rat under oxidative stress

Heart diseases, which are related to oxidative stress (OS), negatively affect millions of people from kids to the elderly. Titanium dioxide (TiO2) has widespread applications in our daily life, especially nanoscale TiO2. Compared to the high risk of particulate matter (≤2.5μm) in air to heart disease patients, related research of TiO2 on diseased body is still unknown, which suggest us to explore the potential effects of nanoscale and microscale TiO2 to heart under OS conditions. Here, we used alloxan to induce OS conditions in rat, and investigated the response of heart tissue to TiO2 in healthy and alloxan treated rats. Compared with NMs treatment only, the synergistic interaction between OS conditions and nano-TiO2 significantly reduced the heart-related function indexes, inducing pathological changes of myocardium with significantly increased levels of cardiac troponin I and creatine kinase-MB. In contrast with the void response of micro-TiO2 to heart functions in alloxan treated rats, aggravation of OS conditions might play an important role in cardiac injury after alloxan and nano-TiO2 dual exposure. Our results demonstrated that OS conditions enhanced the adverse effects of nano-TiO2 to heart, suggesting that the use of NMs in stressed conditions (e.g., drug delivery) needs to be carefully monitored.

Hypoglycemic effect of oral crude tea flower polysaccharides on alloxan modeling Sprague–Dawley rats and the possible mechanism

This article mainly focused on the hypoglycemic effects of green tea flower polysaccharides (TFPS) and their possible mechanisms about regulating concentration of blood glucose. An alloxan-induced Sprague–Dawley (SD) rat model was used to observe the change in blood glucose. Inhibition rate of α-amylase and α-glucosidase, and antioxidant ability of TFPS were also tested to explain the possible mechanism. The results showed that TFPS could reduce blood glucose in alloxan-treated rats. TFPS had strong hydrogen donor ability and could protect cell membrane from overoxidation. TFPS could also inhibit the activity of α-amylase and α-glucosidase in vitro. But the inhibition of α-amylase by TFPS was comparatively low. It suggested that TFPS could protect against rapid blood glucose rise in alloxan-induced SD rats. The possible mechanism was that TFPS not only could donate hydrogen to protect SD rats from oxidative damage, but also inhibit digestive enzymes activities.

Evaluation of the Hypoglycemic Activity of Cucumis metuliferus (Cucurbitaceae) Fruit Pulp Extract in Normoglycemic AlloxanInduced Hyperglycemic Rats

The hypoglycemic effects of the fruit extract of C. metuliferus was investigated in normoglycemic and alloxan-induced hyperglycemic rats. The results showed that there was an insignificant (P > 0.05) decrease in the blood glucose concentration of normoglycemic rats treated with oral doses of 1000 and 1500 mg/kg of the extract. On the other hand, 500 mg/kg of the fruit extract produced an insignificant (P > 0.05) decrease in blood glucose levels of alloxan-treated rats, while 1000 and 1500 mg/kg oral dose points produced a significant (P < 0.05) decrease in the blood glucose concentration of hyperglycemic rats comparable to that produced by tolbutamide. From this study, the data suggested that the fruit extract did not alter the BGC level in normoglycemic rats, but had a potential hypoglycemic property in alloxan-induced hyperglycemic rats.

Expression pattern of thermogenesis-related factors in interscapular brown adipose tissue of alloxan-treated rats: Beneficial effect of l-arginine

Metabolic abnormalities underlying diabetes can be abrogated by l-arginine. Here we examined the molecular basis of disturbed interscapular brown adipose tissue (IBAT) thermogenesis and the possible role of nitric oxide (NO) in the IBAT of diabetic rats. To induce diabetes, adult Mill Hill hybrid hooded male rats were given a single alloxan dose (120 mg/kg). Both non-diabetic and diabetic groups were further divided into three subgroups receiving: (i) l-arginine·HCl (2.25%) or (ii) N ω-nitro- l-arginine methyl ester ( l-NAME·HCl, 0.01%) for 12 days in drinking water and (iii) untreated controls. Treatment of the diabetic animals started after diabetes induction (glucose level ⩾12 mmol/L). Diabetes led to a decrease in the mRNA levels of uncoupling protein 1 (UCP1), peroxisomal proliferator activator receptor gamma (PPARγ) and endothelial NO synthase (eNOS) as revealed by RT-PCR. The diabetic rats had reduced eNOS and inducible NOS (iNOS) protein contents accompanied by low tissue vascularization, a parameter directly related to tissue thermogenic state. Downregulation of glutathione peroxidase (GSH-Px) and catalase (CAT) transcripts were also observed in diabetes. In contrast, the expression level of PPARγ coactivator-1α (PGC-1α) mRNA was elevated. Supplementation with l-arginine not only restored diabetes-induced changes in the expressions of these molecules important for IBAT regulation, but also increased the vascularity. Interestingly, l-NAME induced similar patterns of changes in vascularity and PGC-1α mRNA level as did l-arginine. In summary, our results provide insight into the molecular basis underlying diabetes-induced metabolic and functional disturbances in the IBAT and suggest a beneficial role for the l-arginine–NO production pathway.