Comparative study on the effect of antioxidants alpha-lipoic acid and N-acetyl cysteine on the structure of the renal tubules of diabetic rabbits

Hyperglycemia-induced oxidative stress plays a central role in the pathogenesis of diabetic complications. The therapeutic potential of antioxidants in the prevention and treatment of these complications is an emerging research area. The roles of alpha-lipoic acid [ALA] and N-acetyl cysteine [NAC] in the protection against oxidative stress in alloxan-induced diabetic rabbits were assessed both biochemically and histologically in this study. Thirty-two mature male rabbits were used in this study. They were divided into two groups: the control group [n=8] and the experimental [n=24] group; the experimental group was injected intraperitoneally with alloxan [180mg/ml/kg body weight]. After 3 weeks, this group [diabetic rabbits] was subdivided into three subgroups of eight rabbits each. The first one was left as the untreated diabetic subgroup; rabbits in the second and third subgroups were treated daily for 7 days with ALA and NAC [100 mg/ml/kg body weight], respectively. At the end of the experiment, blood and kidney sections were processed for biochemical and histological studies. The renal tubules showed degenerative and apoptotic changes, which were associated with increased DNA fragmentation and lipid peroxidation in the kidney tissues, as well as reduction in the capacity of the antioxidant defense system. However, treatment of diabetic rabbits with either ALA or NAC ameliorated diabetes-induced oxidative stress. ALA and NAC could be useful in the prevention and treatment of oxidative stress associated with hyperglycemia. This action seems to result mainly from direct scavenging of reactive oxygen species and restoring of the GSH [glutathione] redox state

Pathomorphological effects of alloxan induced acute hypoglycaemia in rabbits

Alloxan is one of the frequently used beta-cytotoxic agents for the induction of Type-1 diabetes mellitus in animal models and is the drug of choice in rabbits. Its beta-cytotoxic action results in a sudden release of insulin leading to severe hypoglycaemia and even mortality if glucose therapy is not given. In the present investigation the pathological effects of alloxan induced acute hypoglycaemia were studied in rabbits. New Zealand White rabbits, 1-1.5 kg body weight, were administered alloxan@100 mg/kg b.w., as a single intravenous dose. Blood glucose levels were monitored [0 h, 20 min, 1 h, and then hourly up to 5 h] and clinical signs noted. Rabbits dead due to hypoglycaemia were necropsied and histopathology performed. Severe histopathological changes were observed especially in the brain [neuronal degeneration and necrosis], kidneys [nephrosis, nephritis] and liver [hepatosis, hepatitis] and also, other organs. Histopathological observation of beta-cytolysis was suggestive that the drug induced hypoglycaemia is insulin mediated. It was concluded that acute hypoglycaemia causes severe pathological changes and the alloxan induced immediate hypoglycaemia if not managed in time, might exacerbate the pathological effects of hyperglycaemia in the induced diabetic models

[Comparison of the toxic effects related to experimental induction of diabetes by Alloxam and Strepytozotocin in rats]

Both Alloxan and Streptozotocin [STZ] are selective substances used to induce experimental diabetes, because they have an important property to damage beta-cells that secrete insulin in Pancreas. But their use has some problems; they have toxic effects on important body organs and also cause some necrosis in tissue. The aim of this study was to clarify the best way of administration, so we examine the acute way which includes giving a single high dose of both the previous materials. Indeed, we also examine a gradual way that includes giving the substances in repeated low doses with intervals last for several days. We measured the changes of weight, the elevation in blood sugar and the mortality for both previous ways. Indeed, a histological study was performed for important body's organ following the administration of the mentioned materials in the gradual way. The findings indicated clearly that the gradual way for both Alloxan and STZ was more safe and effective than acute administration. STZ was best from Alloxan especially in the gradual way concerning the inducing of diabetes and the low mortality. According to these results we recommend to use STZ with the gradual way in the researches that require experimental diabetic animals

Effect of alloxan-induced diabetes mellitus and ethanol on pregnancy outcome in mice / Efeito do diabetes mellitus induzido por aloxana e etanol na gestação de camundongos

INTRODUCTION AND OBJECTIVES: To investigate the effects of ethanol, diabetes mellitus and the combination of both on mouse fetuses. METHODS: We used 24 female Swiss mice, dividing them into four groups of 6 each: control (C), ethanol (E), diabetes (D) (blood glucose > 200 mg/dL) and diabetes + ethanol (DE). Diabetes was induced by alloxan (40 mg/kg) on day 7 of pregnancy. Groups E and DE received 4 g/kg of 25 percent v/v ethanol intraperitoneally, whereas groups C and D received saline. On day 18, all fetuses were harvested. RESULTS: In group DE the following anomalies were found: exencephaly, situs inversus totalis, situs inversus partialis, eyelid skin tag and one animal from group E had pulmonary artery hypoplasia. Ethanol administration partially reverted diabetes-fetal resorption caused by diabetes, yet it induced late fetal death. Both diabetes and ethanol reduced placental diameter and increased its weight. Ethanol had more effect on fetal length in males than in females, however, such bias was not found for diabetes. Ethanol prevented diabetes-induced tail shortening in both genders. CONCLUSIONS: These results show that, although ethanol might improve energy metabolism in early gestation, it causes cell damage that leads to cardiovascular, limb and neural tube defects, late fetal death and reduced placental size.

INTRODUÇÃO E OBJETIVOS: Investigar o efeito do etanol, do diabetes mellitus (DM) e da associação de ambos sobre os fetos de camundongo. MÉTODOS: Foram utilizadas 24 fêmeas de camundongos Swiss divididas em quatro grupos de seis animais cada: controle (C); etanol (E); diabetes (D) (glicemia > 200 mg/dl), e diabetes + etanol (DE). O diabetes foi induzido pela aloxana (40 mg/kg) no dia 7 da gestação. Os animais dos grupos E e DE receberam 4 g/kg de solução a 25 por cento v/v de etanol intraperitoneal (IP), enquanto os animais dos grupos C e D receberam salina. No dia 18, todos os fetos foram coletados. RESULTADOS: Foram encontradas as seguintes anomalias no grupo DE: exencefalia, situs inversus totalis, situs inversus partialis e apêndice cutâneo palpebral. Um animal do grupo E apresentou hipoplasia da artéria pulmonar. A administração de etanol reverteu parcialmente a reabsorção fetal induzida pelo diabetes, porém aumentou a morte fetal tardia. Ambos, diabetes e etanol, reduziram o diâmetro placentário e aumentaram o seu peso. O etanol teve mais efeito no comprimento de fetos machos, contudo isso não ocorreu com o diabetes. O etanol preveniu a redução da cauda induzida pelo diabetes em ambos os sexos. CONCLUSÃO: Esses resultados indicam que, embora o etanol possa melhorar o metabolismo energético no início da gestação, ele causa lesão celular que leva a defeitos cardiovasculares, dos membros e do tubo neural, além de morte fetal tardia e redução do tamanho da placenta.

Hypoglycemic and other related effects of Boswellia glabra in alloxan-induced diabetic rats.

The hypoglycemic effect of the aqueous extract of the leaves and roots of Boswellia glabra was examined using alloxan-induced diabetic rats. A single oral administration of Boswellia glabra leaf and root extract decreased the blood glucose level. The continued use of leaf and root extract for 28 days produced significant hypoglycemic effects; also there was a decrease in serum glucose, cholesterol, triglyceride, urea and creatinine levels and enzyme activities (alkaline phosphatase and glucose-6-phosphatase). Ultra structural studies of beta cell of alloxan-induced diabetic rats treated with root extract showed numerous granulated sacs in comparison to rats treated with leaf extract. Thus, rats treated with root extract showed less degranulated sacs and more number of filled secretory granules in comparison to diabetic rats. Thus the use of aqueous extract of Boswellia glabra increased the synthesis of secretory granules in the beta-cell.

Antioxidant activity of Albizzia lebbeck (Linn.) Benth. in alloxan diabetic rats.

There is an increasing demand for natural anti-diabetic drugs, as continuous oral administration of insulin can culminate in many side effects and toxicity. In our endeavour to formulate some cost-effective herbal medicines for diabetes, we undertook this study to evaluate the antioxidant potential of aqueous extract of Albizzia lebbeck (ALL) in diabetic rats. The oxidative stress in alloxan-induced diabetic rats was determined by estimating the levels of thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and reduced glutathione (GSH) in liver and kidneys. Activities of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione S transferase (GST) were assessed in diabetic as well as rats co-administered with ALL. Oxidative damage in the liver and kidneys of diabetic rats as evidenced by a marked increment in the levels of TBARS and CD, and also a distinct diminution in GSH content was nullified by ALL, as these parameters showed a tendency to retrieve towards normalcy on co-administration of the herbal drug. The antioxidant enzymes registered a decline in activity in diabetic rats thus revealing the damaging effects of free radicals generated due to alloxan exposure. The activities of these enzymes returned to normalcy in ALL-administered rats indicating the antioxidant efficacy of the drug in resisting oxidative insult. The findings provide a rationale for further studies on isolation of active principles and pharmacological evaluation.

Hypolipidimic effect of some medicinal plants on diabetic rats

Our aim was to evaluate the hypolipidimic effect of aqueous extract of a famous mixture used in Saudi Arabia folk medicine that consists of Nigella sativa, Commiphora myrrha, Boswellia carterii Birdw, Ferule assa-foetida and Aloe vera and also the extract of each plant alone on alloxan induced diabetic rats. The present study was carried out on 80 adult male albino rats [120 +/- 20 g.b.wt.], the rats were divided randomly into 8 groups, the first group served as control group, the second group as alloxan induced diabetic rats, the third group was diabetic rats treated with mixture of folk medicinal plant [0.01g /100 g b. wt.] ,the fourth group: diabetic rats treated with Nigella sativa [0.01g /100 g b. wt.], the fifth group: diabetic rats treated with Aloe vera [0.005g /100 g b. wt.], the sixth group: diabetic rats treated with Ferule assa-foetida [0.01 g /100 g b. wt.], the seventh: diabetic rats treated with Boswellia carterii Birdw [1ml/100 g b. wt.] and the eighth group: diabetic rats treated with Commiphora myrrha [0.01 g ml/100 g b. wt.]. Serum total lipid, serum total cholesterol, LDL-cholesterol, and triglyceride recorded significant increases in diabetic, Nigella sativa, Commiphora myrrha, Boswellia carterii birdw and Aloe vera treated group. While the mixture and Ferule assa-foetida treated group, showed insignificant changes in serum total lipid, triglyceride, serum total cholesterol and LDL-cholesterol. On other hand, the mixture treated group and Ferule assa-foetida treated group showed significant decreased in the previous parameters. The serum HDL cholesterol was significantly reduced in diabetic group throughout the experimental periods, otherwise, all treated group revealed insignificant changes till the end of experiment when compare with undiabetic rats. The aqueous extract of a mixture consists of Nigella sativa, Commiphora myrrha, Boswellia carterii Birdw, Ferule assa-foetida and Aloe vera are useful for improvement of the lipid profile of alloxan induced diabetic rats from each plant alone

Níveis glicêmicos e de colesterol em ratos com Diabetes mellitus aloxano induzido, tratados com infusäo de Bauhinia candicans ou Syzygium jambolanum / Glucose and cholesterol plasma levels in rats with alloxan-induced Diabetes mellitus treated with infusion of Bauhinia candicans or Syzygium jambolanum

Este estudo verificou a eficiência de infusäo de duas plantas usadas na medicina popular, Syzygium jambolanum (Sj) e Bauhinia candicans (Bc). Sessenta (60) ratos adultos, machos, da linhagem Wistar, pesando entre 220 e 240g, foram submetidos à induçäo de Diabetes mellitus insulino dependente (DMID) com Aloxano. O estudo foi dividido em dois experimentos. No primeiro, 15 ratos receberam a administraçäo de Aloxano na dosagem de 40mg/kg em dose única e no segundo, 60mg/kg uma vez ao dia, durante três dias, ambos por via intraperitonal. A hiperglicemia foi confirmada no terceiro dia de cada experimento. Após esta confirmaçäo, os animais foram divididos aleatoriamente em três grupos de cinco e quinze animais para o primeiro e segundo experimento, respectivamente. O grupo 1 (C) serviu como controle, o grupo 2 (TI) recebeu infusäo de Sj "ad libitum" como fonte líquida e o grupo 3 (TII) recebeu infusäo de Bc, por um período de 21 e 40 dias, para o primeiro e segundo experimento, respectivamente. A colheita de sangue foi realizada por punçäo do plexo venoso retro-orbitário com os animais anestesiados, nos dias 3, 9, 16 e 23 do primeiro experimento e nos dias 3, 16, 24 e 40 do segundo. Após vinte e um dias da fase de tratamento, o grupo TI do primeiro experimento apresentou marcante reduçäo de hiperglicemia (P < 0,001). Esta mesma observaçäo foi verificada no grupo TI do segundo experimento aos dezesseis dias da fase de tratamento (P < 0,004), estendendo-se até os quarenta dias (P < 0,0001), quando comparado ao grupo controle. Simultaneamente, sinais clínicos de DMID, como polifagia e polidipsia foram reduzidos neste grupo. O colesterol plasmático demonstrou aumento moderado somente nos animais do segundo experimento, näo sendo observado o efeito do tratamento com infusäo Sj e Bc sobre a colesterolemia dos animais em estudo. No 40§ dia de ambos os experimentos, os animais foram eutanasiados e foram colhidas amostras de pâncreas e fígado para avaliaçäo histopatológica. A análise histopatológica das amostras de pâncreas e fígado do experimento I näo demonstrou diferença entre os grupos tratados e o grupo C. No entanto, no experimento II, nove em dez amostras do grupo C e cinco em nove amostras do grupo TII apresentaram necrose de células das ilhotas de Langerhans do pâncreas, enquanto que somente duas das nove amostras do grupo TI apresentaram necrose de células das ilhotas de Langerhans. Os resultados obtidos neste estudo permitem concluir que ...

Effect of D-400, a herbal formulation, on blood sugar of normal and alloxan-induced diabetic rats.

Blood sugar levels of normal rats treated with D-400 showed significant reduction (P < 0.05) as compared to control groups. The fall was seen at one month and remained so uptill 3 months. Hyperglycemic response to adrenaline was significantly lowered (P < 0.05) following D-400 treatment. D-400 potentiated the hypoglycemia following tolbutamide treatment. Blood sugar remained persistently low in tolbutamide plus D-400 treated group after 3 and 4 hours (P < 0.05). In the alloxan-induced diabetic rats, a significant lowering of blood and urinary sugar was noticed on day 20, 30 and 40 following treatment with D-400 (P < 0.05). Liver glycogen depletion was significantly inhibited in the D-400 treated group (P < 0.025). D-400 has significantly potentiated (P < 0.05) the hypoglycemic action of insulin in alloxan-induced diabetic rats.

Histological and histochemical studies on the effect of alloxan induced diabetes on the skeletal muscles of the rabbit

The present work deals with the histological and histochemical changes in the rabbit gastrocnemius muscle fibers due to alloxan induced diabetes. Thirty healthy male New Zealand rabbits were utilized. The rabbits were divided into two groups; The Animals of the control group [ten rabbits] were injected singly with sterile saline [1 mI/kg body weight] in their ear veins. Each animal of the experimental diabetic group [twenty animals] was injected with a single dose of Alloxan [100 mg dissolved in 1 mI sterile saline/kg body weight] in 1 st ear vein to induce diabetes. The experimental group was further subdivided into two subgroups; [a] Subgroups B: were sacrificed 8 weeks after Alloxan injection. 1b] Subgroup B: they were sacrificed 16 weeks after Alloxan injection. Specimens from gastrocnemius muscles of all animals were prepared for histochemical staining. Other specimens were also prepared for transmission electron microscope examination. The collagen fibers between the muscle fibers were increased in diabetic animals. Electron microscopy revealed a marked decrease in the number of mitochondria, the cristae of which were also diminished or oven lost, moreover, the electron-dense granules in the mitochondrial matrix were increased. Thickening of the basement membrane of the muscle capillaries was also noticed in the diabetic animals. Regarding the histochemical changes of the muscle fibers of diabetic animals; it was found that the glycogen content of these fibers was deceased, while the lipid content was unchanged. The activities of both, Alkaline phosphatase and Acid phosphatase enzymes were increased, but the activity of Succinc dehydrogenase enzyme was markedly diminished. No changes could be detected in the activity of Adenosine triphosphatase enzyme in the diabetic muscle fibers. This work concluded that diabetes mellitus has serious effects of the muscle fibers affecting mainly the mitochondria and the oxidative enzymes resulting in weak contractility and rapid fatigue of the muscles

Histological and histochemical study of alloxan induced diabetes on the liver of rabbit

In the present study thirty rabbits were used and divided into control group [A] and two experimental groups B and C injected with 100mg/kgm body weight of alloxan. The animals of group B were sacrificed eight weeks after injection while those of group [C], were sacrificed after sixteen weeks of injection. The dissected liver was fixed in 10% formal saline and processed for routine paraffin technique. The obtained sections were stained with haematoxylin and eosin. Masson trichrome, PAS technique. Bests carmine and Gomori calcium phosphate for alkaline phosphatse. Examination of the liver sections of control group [A] revealed classical structure of hepatic lobule with great amount of glycogen granules. Alkaline phosphatase activity was weak. Liver sections of diabetic rabbits for 8 weeks showed mild inflammatory reaction with condensation of collagen fibers in the portal tract. Glycogen content decreased and alkaline phosphatase activity was moderate. Sixteen weeks after injection of alloxan vacuolation of liver cells, marked condensation of collagen fibers in portal tract and periportal region and decreased glycogen content were observed. The activity of alkaline phosphatase was moderate. This study concluded that, untreated diabetes mellitus could lead to a destructive effect on liver cells and their enzymes