Diabetes Mellitus In Experimental Animals Research Articles

Subtle Intricacies Identified during Streptozotocin-Induced Diabetes in Wistar Rats

Abstract: Aim: This study aimed to establish the dose of streptozotocin required to induce Type -1 diabetes in Wistar rats. Background: Streptozotocin is currently employed worldwide to induce insulin-dependent diabetes mellitus also known as Type 1 diabetes mellitus in experimental animals. Though many reports on the use of streptozotocin induction of diabetes are reported in the literature, they were not reproducible. Moreover, there was no mention of the mortality associated with the same as well as the conditions followed during the study. Materials and Methods: In the present study, the dose, route, and solvent used for streptozotocin were investigated. Various doses of streptozotocin 55, 50, 40, and 35mg/kg dissolved in either freshly prepared cold 10mM sodium citrate buffer (pH 4.5) or normal saline solution was administered intraperitoneally as well as intravenously. For intraperitoneal administration, the dose-volume was 10mL/kg whereas for intravenous administration the dose-volume was 2mL/Kg. Different routes were employed to ascertain the cause of mortality for which an autopsy was performed. Besides mortality rate was also determined. Results and Discussion: The findings of the study revealed that a 35-40mg/kg dose of streptozotocin showed less percentage mortality and successful induction of diabetes. Conclusion: Mortality (10-20%) was observed at a dose of 35-40mg/kg streptozotocin. Therefore, streptozotocin (35-40mg/kg) was confirmed to be safe and effective for the induction of diabetes in Wistar rats. This paper highlights subtle intricacies observed during induction of diabetes in Wistar rats using streptozotocin Keywords: Male Wistar rats, Streptozotocin, Type-1 diabetes, 5% dextrose, Mortality, Normal saline solution.

Histopatologi Organ Pankreas Tikus DM tipe 2 yang diberi Ekstrak Etanol Daun Gedi Merah (Abelmoscus manihot L. Medik)

Gedi Merah leaf (Abelmoschus manihot L.Medik) is a tropical plant used by the community as a traditional medicine to reduce cholesterol, hypertension, and antidiabetic levels. Diabetes mellitus is a disorder of carbohydrate, protein, and fat metabolism due to a lack of the hormone insulin so that glucose in the blood increases which is characterized by changes in the histopathological structure of the pancreatic islets of Langerhans. The purpose of this study was to see the histopathological description of the pancreas in male white rats (Rattus norvegicus) Wistar strain model of type II diabetes mellitus by administering ethanol extract of red gedi leaves (Abelmoschus manihot L.Medik). Modeling of diabetes mellitus in experimental animals was carried out by administering a high-fat diet and intraperitoneal induction of streptozotocin 30 mg/kg. After modeling, male rats were grouped into 6 treatment groups, namely a normal control group, a positive control group, a negative control group, and a group that was given the ethanol extract of red gedi leaves at a dose of 75 mg/kg BW, 150 mg/kg BW 300 mg/kg BW. The results of the histopathological examination of the pancreas and the number of endocrine cells showed that the ethanolic extract of red gedi leaves (Abelmoschus manihot L.Medik) was effective in repairing pancreatic cells and regenerating endocrine cells in the islets of langerhans.

Morphological features of the large intestine in experimental acute generalized peritonitis against the background of streptozotocin-induced diabetes

The work is a fragment of the research project “Pathogenetic features of the allergic and inflammatory processes course and their pharmacocorrection”, conducted by the Department of Pathological Physiology, Danylo Halytskyi Lviv National Medical University (state registration No. 0116U004503).
 The aim of the work: to study the morphological features of the colon in the dynamics of the development of experimental acute peritonitis on the background of streptozotocin-induced diabetes mellitus.
 Materials and Methods. The experiment used 48 white male rats. Diabetes mellitus in experimental animals was simulated by a single intraperitoneal injection of streptozotocin (Sigma) at a rate of 60 mg/kg, acute disseminated peritonitis – the introduction of 0.5 ml of 10 % filtered fecal suspension into the abdominal cavity. A morphological study of the colon in animals removed from the experiment on the first, third and seventh days of acute peritonitis on the background of concomitant diabetes mellitus was performed.
 Results and Discussion. Morphological examination of the colon of animals on the first day of experimental acute peritonitis in conditions of concomitant streptozotocin-induced diabetes mellitus revealed an increase in the size of the crypts due to stroma edema and lymphohistiocytic infiltration, slight perivascular edema in the subclavian edema. On the third day, thickening of the mucous membrane of the colon, a sharp increase in the depth of the crypts, uneven blood supply to the vessels in the submucosal layer with a predominance of perivascular edema were verified. On the seventh day, a decrease in the thickness of the mucous membrane due to the expansion of the crypts was visualized. Part of the epitheliocytes was in a phase of increased secretory activity, the other part was dystrophically altered, which stimulated increased lymphocytic and histiocytic infiltration.
 These changes were accompanied by activation of reactive processes and hyperplasia of lymphoid follicles on the first day of peritonitis on the background of streptozotocin-induced diabetes mellitus, and as the severity of purulent inflammation – hypoplasia of the lymphoid tissue and a decrease in local reactivity(the third and seventh days of the development of acute peritoneal burning in conditions of combined pathology).

Relationship between lipid peroxidation and antioxidants in rats with experimental acute generalized peritonitis against the background of streptozotocin-induced diabetes

Introduction. There are evidence that oxidative stress is involved in the pathogenesis of the acute generalized peritonitis and diabetes mellitus.The aim of study was to examine levels of the products of lipid peroxidation and the antioxidants in rats with experimental acute generalized peritonitis against the background of streptozotocin-induced diabetes.Material and methods. The experiment was performed on 66 adult white male rats weighing 220-300 g. Diabetes mellitus in experimental animals was simulated by a single intraperitoneal injection of streptozotocin (Sigma) at the dose of 60 mg/kg. Acute generalized peritonitis was induced with 10% faecal suspension in a dose of 0.5 ml per 100 g of animal weight in the abdominal cavity of laboratory animals by puncture method. The thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOHs), superoxide dismutase (SOD) activity, catalase (CAT) and ceruloplasmin (CP) were estimated and compared.Results. Our results showed that during all stages of development of acute generalized peritonitis on the background of streptozotocin-induced diabetes there is the LOOHs decrease and the TBARS increase. We observed statistically significant inverse correlations between the level of LOOHs and SOD in the animals of subgroup 1 (r = -0.88; p <0.05) and inverse correlations between the TBARS level and the SOD level in the subgroup 3 of animals (r = -0.74; p <0.05). We also found a statistically significant inverse correlation between the CAT level and the TBARS level (r = -0.86; p <0.05) and between the CP level and the TBARS level in the blood of animals in the subgroup 3 (r = -0.87; p <0.05).Conclusion. Negative statistically significant correlations between the TBARS level and the antioxidants (SOD, CAT, CP) in the blood of animals with acute generalized peritonitis on the background of streptozotocin-induced diabetes indicate a predictor role of lipid peroxidation processes in the depletion of antioxidant resources

THE EFFECT OF CHRONIC HYPERGLYCEMIA ON THE STATE OF MUSCULOSKELETAL SYSTEM (LITERATURE REVIEW)

Diabetes mellitus is a metabolic disorder that today has become a threatening problem for human health. Its prevalence has been constantly increasing throughout the world over the past decades. Diabetes mellitus is regarded as an incurable metabolic disorder characterized by hyperglycemia, which is caused by defects in insulin secretion. This disease annually affects almost 3% of the total population of the planet. Chronic hyperglycemia causes dysfunction of various organs of the body, such as the eyes, kidneys, heart, blood vessels, and nerves. The most common complications of diabetes include lesions of the vessels of the eye, kidneys, lower limbs and nervous system. A high level of glucose in the blood causes the development of a wide range of pathological disorders, which affect bones as well. Recent studies have shown that diseases of the skeletal system are often observed in diabetes mellitus. Speaking about the effect of hyperglycemia on bones, the development of osteopenia and osteoporosis should be noted. In this regard, an important area of research is to study changes in the bone tissue in patients with type 1 diabetes mellitus and the mechanisms that lead to disruption of bone structure and metabolism. The article highlights the pathophysiological mechanisms of hyperglycemia action in type 1 diabetes that explains complex disorders of the organs of the musculoskeletal system. The detrimental effect of hyperglycemia results in marked degenerative changes in bone cells. The pathogenic effect of hyperglycemia on bone tissue is manifested in a decrease in bone mineral density that is due to the lack of insulin and, as a consequence, significant metabolic disorders, a decrease in bone mass, inhibition of bone tissue formation, a significant decrease in the trace element composition of bone. The combination of these factors creates the appropriate pathomorphological basis for the development of diabetic osteopathy. The article highlights the mechanism of action of hyperglycemia on skeletal system in order to stimulate to a more detailed investigation of diabetes mellitus in experimental animals.

Arachidonic Acid Has Anti-Inflammatory and Anti-Diabetic Actions In Vitro and In Vivo

Abstract Objectives To evaluate the effect of arachidonic acid (AA) in the pathobiology of chemical-induced type 1 and type 2 diabetes mellitus in experimental animals. Methods In vitro studies were performed using RIN 5F cells and animal studies in 3–4 week old Wistar rats. Alloxan and streptozotocin (STZ) were used to induce type 1 diabetes and STZ employed to induce type 2 diabetes mellitus. RIN5F cell proliferation was measured using MTT assay. Establishment of alloxan and STZ-induced diabetes in animals was confirmed by measuring plasma glucose levels. Plasma insulin, IL-6, TNF levels were measured by ELISA. Expression of cyclo-oxygenase-2, lipoxiygenase, NF-kB and IkB genes was performed in pancreatic and adipose tissues. Results Alloxan and STZ-induced cytotoxicity to RIN5F cells was inhibited by arachidonic acid that was not blocked by both COX and LOX enzymes. Alloxan and STZ-induced type 1 diabetes mellitus and STZ-induced type 2 diabetes was prevented by arachidonic acid treatment. Plasma levels of glucose, insulin, IL-6 and TNF and expressions of NF-kB, IkB, COX-2, LOX in pancrreatic and adipose tissues and lipocalin-2 in adipose tissue were restored to normal by arachidonic acid treatment. AA treatment enhanced plasma lipoxin A4 (LXA4) levels. LXA4 also prevented both type 1 and type 2 diabetes induction by STZ. Conclusions AA prevented the development of both type 1 and type 2 diabetes mellitus in Wistar rats and protected pancreatic beta cells form the cytotoxicity of alloxan and STZ. AA showed strong anti-inflammatory actions. AA seems to bring about its anti-inflammatory and anti-diabetic actions by enhancing LXA4 formation. Funding Sources None.

Antidiabetic effect of olive leaf extract on streptozotocin-induced diabetes mellitus in experimental animals.

Background: recently, a relationship between diabetic complications and oxidative stress has been emphasized. There have been some studies showing the effect of olive leaf on hyperglycemia and diabetic complications due to its antioxidant properties. In many studies the effect of olive leaf on plasma total antioxidant level has been measured by different methods. Our study represents the first time it has been measured by a new method of total thiol disulfide homeostasis. Aim: chronic exposure to hyperglycemia and hyperlipidemia contributes to the pathogenesis of diabetic complications through oxidative stress mediators. Thiol is one of the most important antioxidant barriers in humans, and thiol disulfide homeostasis is a new oxidative stress marker. We aimed to investigate the effect of olive leaf extract (OLE) obtained from fresh leaves of Olea europaea, var oleaster on diabetic complications through their hypoglycemic and antioxidant effect in diabetic rats. Methods: twenty-eight Wistar albino rats aged 12-13 weeks were used in the study. The rats were divided into a control group (C), a diabetic control group (DC), a diabetic group treated with 200 mg/kg OLE (D+200), and a diabetic group treated with 400 mg/kg OLE (D+400), having 7 rats in each group. The treatment groups received OLE by the gavage method for 21 days. At the end of the study, all rats were sacrificed by cervical dislocation. Blood samples collected from the heart were centrifuged and glucose, total cholesterol, triglyceride, urea, uric acid, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lipid hydroperoxide (LOOH) level, and thiol-disulfide homeostasis were determined. The hemoglobin A1c (HbA1c) analysis was performed on complete blood. In addition, a tail flick test and hot plate modeling were performed to indicate pain perception loss. Results: it was observed that OLE had no effect on serum glucose and HbA1c levels. On the contrary, OLE reduced the levels of total cholesterol (p < 0.01), urea (p < 0.01) and hot plate latency (p < 0.01) in a significant manner. Also, OLE showed a tendency to reduce LOOH levels and to increase thiol levels in a dose-dependent manner (p > 0.05). Conclusion: OLE supplementation for 21 days, at the amounts used, cannot protect against hyperglycemia but may be protective against hypercholesterolemia and tissue damage as caused by diabetes mellitus in rats.

Biochanin A improves insulin sensitivity and controls hyperglycemia in type 2 diabetes

Biochanin A (5,7-Dihydroxy-4′-methoxyisoflavone) is an O-methylated isoflavone known for its anti-inflammatory, lipid lowering and anti-cancer activity. The current study was designed to find out antidiabetic efficacy of Biochanin A in type 2 diabetes in rats.Induction of type 2 diabetes mellitus in experimental animals was carried out by manipulation of diet using high fat diet for fourteen days and then administration of streptozotocin at low dose of 35 mg/kg, i.p. The diabetic animals were treated with 10, 20 and 40 mg/kg of Biochanin A for 28 days. The effect of Biochanin A treatment in diabetic animals was evaluated by measuring changes in body weight, biochemical parameters, insulin sensitivity index, Homeostatic model assessment-Insulin resistance (HOMA-IR), oral glucose tolerance test, glycohaemoglobin and hepatic glycogen level. Changes in histopathological characteristics of pancreatic tissue were also evaluated after treatment with Biochanin A. Immunohistochemical analysis of pancreatic tissue was carried out for the expression of SIRT1.The results showed that the selected doses of (10, 20 and 40 mg/kg) Biochanin A significantly decreased blood glucose (p < 0.001). The higher dose (40 mg/kg) of Biochanin A significantly reduced glucose tolerance (p < 0.001) in diabetic animals. Biochanin A treatment significantly reduced insulin resistance (p < 0.001) and improved inulin sensitivity (p < 0.01 for 10 mg/kg, 20 mg/kg, p < 0.001 for 40 mg/kg) at all selected dose levels. It also improved lipid profile significantly (p < 0.001) at lower, middle and higher dose level. Glycohaemoglobin formation was significantly decreased in diabetic animals (p < 0.001) after treatment with Biochanin A at all three dose levels. Liver glycogen level was also improved significantly after treatment with Biochanin A in diabetic animals at 20 mg/kg and 40 mg/kg dose level. Biochanin A at dose of 40 mg/kg increased SIRT1 expression in pancreatic tissue. In conclusion, Biochanin A has significant effect in type 2 diabetes mellitus which might be linked to its effects on SIRT1.

Arachidonic acid and lipoxin A4 as possible endogenous anti-diabetic molecules

In both type 1 and type 2 diabetes mellitus, increased production of pro-inflammatory cytokines and reactive oxygen species (ROS) occurs that induce apoptosis of β cells and cause peripheral insulin resistance respectively though the degree of their increased production is higher in type 1 and less in type 2 diabetes mellitus. Despite this, the exact mechanism(s) that lead to increased production of pro-inflammatory cytokines: interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and ROS is not known. Studies showed that plasma concentrations of arachidonic acid (AA) and lipoxin A4 (LXA4) are low in alloxan-induced type 1 diabetes mellitus in experimental animals and patients with type 2 diabetes mellitus. Prior administration of AA, eicosapentaenoic and docosahexaenoic acids (EPA and DHA, respectively) and transgenic animals that produce increased amounts of EPA and DHA acids were protected from chemical-induced diabetes mellitus that was associated with enhanced formation of LXA4 and resolvins, while protectin D1 ameliorated peripheral insulin resistance. AA, LXA4, resolvins and protectins inhibit IL-6 and TNF-α production and suppress ROS generation. Thus, AA and lipoxins, resolvins and protectins may function as endogenous anti-diabetic molecules implying that their administration could be useful in the prevention and management of both types of diabetes mellitus.

Suppressive effects of natural reduced waters on alloxan-induced apoptosis and type 1 diabetes mellitus

Insulin-producing cells express limited activities of anti-oxidative enzymes. Therefore, reactive oxygen species (ROS) produced in these cells play a crucial role in cytotoxic effects. Furthermore, diabetes mellitus (DM) development is closely linked to higher ROS levels in insulin-producing cells. Hita Tenryosui Water® (Hita T. W., Hita, Japan) and Nordenau water (Nord. W., Nordenau, Germany), referred to as natural reduced waters (NRWs), scavenge ROS in cultured cells, and therefore, might be a possibility as an alternative to conventional pharmacological agents against DM. Therefore, this study aimed to investigate the role of NRWs in alloxan (ALX)-induced β-cell apoptosis as well as in ALX-induced diabetic mice. NRWs equally suppressed DNA fragmentation levels. Hita T. W. and Nord. W. ameliorated ALX-induced sub-G1 phase production from approximately 40% of control levels to 8.5 and 11.8%, respectively. NRWs restored serum insulin levels (p < 0.01) and reduced blood glucose levels (p < 0.01) in ALX-induced mice. Hita T. W. restored tissue superoxide dismutase (SOD) (p < 0.05) activity but not tissue catalase activity. Hita T. W. did not elevate SOD or catalase activity in HIT-T15 cells. Nord. W. restored SOD (p < 0.05) and catalase (p < 0.05) activity in both cultured cells and pancreatic tissue to normal levels. Even though variable efficacies were observed between Hita T. W. and Nord. W., both waters suppressed ALX-induced DM development in CD-1 male mice by administering NRWs for 8 weeks. Our results suggest that Hita T. W. and Nord. W. protect against ALX-induced β-cell apoptosis, and prevent the development of ALX-induced DM in experimental animals by regulating ALX-derived ROS generation and elevating anti-oxidative enzymes. Therefore, the two NRWs tested here are promising candidates for the prevention of DM development.

Prevention of Chemically Induced Diabetes Mellitus in Experimental Animals by Virgin Argan Oil

The argan tree plays an important socioeconomic and ecologic role in South Morocco. Moreover, there is much evidence for the beneficial effects of virgin argan oil (VAO) on human health. Thus, this study investigated whether administering VAO to rats can prevent the development of diabetes. VAO extracted by a traditional method from the almonds of Argania spinosa (2 mL/kg) was administered orally (for 7 consecutive days) to rats before and during intraperitoneal alloxan administration (75 mg/kg for 5 consecutive days). An alloxan diabetic-induced untreated group and treated by table oil were used as control groups. Body mass, blood glucose and hepatic glycogen were evaluated. In the present study, subchronic treatment with VAO at a dose of 2 mL/kg, before the experimental induction of diabetes, prevented the body mass loss, induced a significant reduction of blood glucose and a significant increase of hepatic glycogen level (p < 0.001) compared with the untreated diabetic group. In conclusion, the present study shows that argan oil should be further investigated in a human study to clarify its possible role in reducing weight loss in diabetics, and even in inhibiting the development or progression of diabetes. This antidiabetic effect could be due to the richness of VAO in tocopherols, phenolic compounds and unsaturated fatty acids.

Antihyperglycemic effect of Coscinium fenestratum and Catharanthus roseus in alloxan-induced diabetic rats

Introduction : Diabetes mellitus, the life-threatening endocrine disorder, affects 170 million people worldwide every year. Statistical projections about India suggest that 57 million Indians will be affected by diabetes mellitus by the year 2025, making the country with highest number of diabetics in the world. Alloxan-induced diabetes mellitus in experimental animals is commonly used to evaluate the antidiabetic effect of medicinal plants and their constituents. The present study has investigated the antidiabetic efficacy of ethanolic extract of Coscinium fenestratum stem and Catharanthus roseus leaves in alloxan-induced diabetic rats. Materials and Methods: Diabetes mellitus was induced in overnight fasted (>8 hours) Wistar rats by single intraperitoneal injection of freshly prepared alloxan monohydrate (150 mg/kg bw) solution in physiological saline. The mechanistic pathway for the antidiabetic potential of these plants was evaluated by analyzing the status of glucose, insulin, C-peptide, glycosylated hemoglobin, activities of carbohydrate-metabolizing enzymes, and glycogen content. The antidiabetic effect of these plant products was also compared with the standard reference drug, glibenclamide. Results: The study revealed that the ethanolic extract of C. fenestratum stem and C. roseus leaves have potent antidiabetic efficacy in alloxan-induced diabetic rats. The antidiabetic efficacy was also much comparable with that of glibenclamide. Conclusions: The present study concludes that the ethanolic extract of C. fenestratum stem and C. roseus leaves have potent antihyperglycemic effect in alloxan-induced diabetic rats. C. fenestratum and C. roseus could therefore be used as an alternative remedy for diabetes mellitus and its complications.

Suppressive effects of electrolyzed reduced water on alloxan-induced apoptosis and type 1 diabetes mellitus

Electrolyzed reduced water, which is capable of scavenging reactive oxygen species, is attracting recent attention because it has shown improved efficacy against several types of diseases including diabetes mellitus. Alloxan produces reactive oxygen species and causes type 1 diabetes mellitus in experimental animals by irreversible oxidative damage to insulin-producing β-cells. Here, we showed that electrolyzed reduced water prevented alloxan-induced DNA fragmentation and the production of cells in sub-G1 phase in HIT-T15 pancreatic β-cells. Blood glucose levels in alloxan-induced type 1 diabetes model mice were also significantly suppressed by feeding the mice with electrolyzed reduced water. These results suggest that electrolyzed reduced water can prevent apoptosis of pancreatic β-cells and the development of symptoms in type 1 diabetes model mice by alleviating the alloxan-derived generation of reactive oxygen species.

Alloxan reduces amplitude of ventricular myocyte shortening and intracellular Ca2+ without altering L-type Ca2+ current, sarcoplasmic reticulum Ca2+ content or myofilament sensitivity to Ca2+ in Wistar rats

Alloxan is widely used to induce diabetes mellitus in experimental animals. Recent studies have provided evidence that alloxan has direct actions on cardiac muscle contraction. The aim of this study was to further investigate the mechanisms underlying the effects of alloxan on ventricular myocyte shortening and intracellular Ca(2+) transport. Amplitude of myocyte shortening was reduced in a dose-dependent manner as the concentration of alloxan was increased in the range 10(-7)-10(-4) M. Amplitude of shortening was reduced (56.8 +/- 6.6%, n = 27) by 10(-6) M alloxan and was partially reversed during a 10 min washout. Amplitude of the Ca(2+) transient was also reduced (79.7 +/- 2.9%, n = 29) by 10(-6) M alloxan. Caffeine-evoked sarcoplasmic reticulum Ca(2+) release, fractional release of Ca(2+), assessed by comparing the amplitude of electrically evoked with that of caffeine-evoked Ca(2+) transients, and fura-2-cell length trajectory during the late stages of relaxation of myocyte twitch contraction were not significantly altered by alloxan. The amplitude of L-type Ca(2+) current was not altered by alloxan. Alterations in sarcoplasmic reticulum Ca(2+) transport, myofilament sensitivity to Ca(2+), and L-type Ca(2+) current do not appear to underlie the negative inotropic effects of alloxan.

The direct effects of streptozotocin and alloxan on contractile function in rat heart

Streptozotocin (STZ) and alloxan (ALX) are widely used to induce diabetes mellitus in experimental animals. The direct effects of STZ and ALX on the amplitude and time course of ventricular myocyte shortening and on cardiac action potentials were investigated. STZ and ALX (10 −5 M) were dissolved in normal Tyrode (NT), maintained at pH 7.4 and 37 °C and stored for either 15 or 60–120 min. Both compounds reduced the amplitude of myocyte shortening. Compared to NT the amplitude of shortening was 34.7 ± 5.0% and 35.2 ± 6.8% with STZ and 41.0 ± 5.5% and 37.3 ± 5.7% with ALX stored for 15 and 60–120 min, respectively. During a 10 min NT washout STZ myocytes recovered to 56.2 ± 8.3% and 60.5 ± 8.2% and ALX myocytes recovered to 88.9 ± 10.0% and 83.7 ± 9.9% after storage of compounds for 15 and 60–120 min, respectively. Perfusion of the whole heart with ALX induced bradycardia but had no effects on the duration of action potential repolarization at 50% and 70% from peak action potential. The negative inotropic effects of STZ and ALX were not altered by storage. The results suggest that some of the effects on heart reported in STZ- and ALX-induced diabetes may be partly attributed to direct action of these compounds.

Differential effect of saturated, monounsaturated, and polyunsaturated fatty acids on alloxan-induced diabetes mellitus

Earlier, we reported that oils rich in ω-3 eicosapentaenoic acid and docosahexaenoic acid and ω-6 γ-linolenic acid and arachidonic acid prevented the development of alloxan-induced diabetes mellitus in experimental animals. Here we report the results of our studies with pure saturated stearic acid (SA), monounsaturated oleic acid (OA) and ω-6 arachidonic acid (AA) on alloxan-induced diabetes mellitus in Wistar male rats. Prior oral supplementation with AA prevented alloxan-induced diabetes mellitus, whereas both SA and OA were ineffective. Cyclo-oxygenase (COX) and lipoxygenase (LO) inhibitors did not block this protective action of AA against alloxan-induced diabetes, suggesting that both prostaglandins and leukotrienes are not involved, and that AA by itself is effective. Furthermore, AA restored the anti-oxidant status to normal range in various tissues. These results suggest that AA protects pancreatic β cells against alloxan-induced diabetes in experimental animals by attenuating oxidant stress.

Effect of prostaglandins against alloxan-induced diabetes mellitus

Previously, we observed that alloxan-induced in vitro cytotoxicity and apoptosis in an insulin secreting rat insulinoma, RIN, cells was prevented by prior exposure to prostaglandin (PG) E 1, PGE 2, PGI 2, PGF 1 α , and PGF 3 α ( P < 0.05 compared to alloxan), whereas thromboxane B 2 (TXB 2) and 6-keto-PGF 1 α were ineffective. In an extension of these studies, we now report that prior intraperitoneal administration of PGE 1, PGE 2, PGF 1 α , and PGF 3 α prevented alloxan-induced diabetes mellitus in male Wistar rats, whereas PGI 2, TXB 2, and 6-keto PGF 1 α were not that effective. PGE 1, PGE 2, PGF 1 α , and PGF 3 α not only attenuated chemical-induced diabetes mellitus but also restored the antioxidant status to normal range in red blood cells and pancreas. These results suggest that PGE 1, PGE 2, PGF 1 α , and PGF 3 α can abrogate chemically induced diabetes mellitus in experimental animals and attenuate the oxidant stress that occurs in diabetes mellitus.

Long-chain polyunsaturated fatty acids and chemically induced diabetes mellitus: Effect of ω-3 fatty acids

In a previous study, we showed that prior oral feeding of oils rich in ω-3 eicosapentaenoic acid and docosahexaenoic acid and ω-6 γ-linolenic acid and arachidonic acid prevent the development of alloxan-induced diabetes mellitus in experimental animals. We also observed that 99% pure ω-6 fatty acids γ-linolenic acid and arachidonic acid protect against chemically induced diabetes mellitus. Here we report the results of our studies with ω-3 fatty acids. Alloxan-induced in vitro cytotoxicity and apoptosis in an insulin-secreting rat insulinoma cell line, RIN, was prevented by prior exposure of these cells to α-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid. Prior oral supplementation with α-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid prevented alloxan-induced diabetes mellitus. α-Linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid not only attenuated chemical-induced diabetes mellitus but also restored the anti-oxidant status to normal range in various tissues. These results suggested that ω-3 fatty acids can abrogate chemically induced diabetes in experimental animals and attenuate the oxidant stress that occurs in diabetes mellitus.

Long-chain polyunsaturated fatty acids and chemically induced diabetes mellitus: Effect of ω-6 fatty acids

Objectives We previously showed that prior oral supplementation of oils rich in ω-3, eicosapentaenoic acid and docosahexaenoic acid, and ω-6, γ-linolenic acid and arachidonic acid, can prevent the development of alloxan-induced diabetes mellitus in experimental animals. But the effect of individual fatty acids on chemically induced diabetes mellitus is not known. We report the results of our studies with ω-6 fatty acids. Methods Alloxan-induced in vitro cytotoxicity and apoptosis in an insulin-secreting rat insulinoma cell line, RIN, was prevented by prior exposure of these cells to linoleic acid, γ-linolenic acid, and arachidonic acid (AA) but not to dihomo-γ-linolenic acid. Cyclo-oxygenase and lipoxygenase inhibitors did not block this protective action of AA. Prior oral supplementation with γ-linolenic acid and pre- and simultaneous treatments with AA prevented alloxan-induced diabetes mellitus. Results Even though pretreatment with linoleic acid and dihomo-γ-linolenic acid and simultaneous treatment with linoleic acid, γ-linolenic acid, and dihomo-γ-linolenic acid did not prevent the development of diabetes mellitus, the severity of diabetes was much less. The saturated fatty acid stearic acid and the monounsaturated fatty acid oleic acid were ineffective in preventing alloxan-induced diabetes mellitus. γ-Linolenic acid and AA not only attenuated chemically induced diabetes mellitus but also restored the antioxidant status to normal range in various tissues. Changes in the concentrations of various fatty acids of the phospholipid fraction of plasma that occurred as a result of alloxan-induced diabetes mellitus also reverted to normal in the AA-treated animals. Conclusions These results suggest that polyunsaturated fatty acids can prevent chemically induced diabetes in experimental animals and attenuate the oxidant stress that occurs in diabetes mellitus.

Genotoxicity of streptozotocin.

Streptozotocin (Streptozocin, STZ, CAS No. 18883-66-4) is a monofunctional nitrosourea derivative isolated from Streptomyces achromogenes. It has broad spectrum antibiotic activity and antineoplastic properties and is often used to induce diabetes mellitus in experimental animals through its toxic effects on pancreatic beta cells. STZ is a potent alkylating agent known to directly methylate DNA and is highly genotoxic, producing DNA strand breaks, alkali-labile sites, unscheduled DNA synthesis, DNA adducts, chromosomal aberrations, micronuclei, sister chromatid exchanges, and cell death. This antibiotic was found to be mutagenic in bacterial assays and eukaryotic cells. STZ is also carcinogenic; a single administration induces tumors in rat kidney, liver, and pancreas. Several lines of evidence indicate that free radicals are involved in the production of DNA and chromosome damage by this compound. Because of the use of STZ as an antineoplastic agent, the study of its genotoxicity has considerable practical significance. The purpose of this review is to present our current knowledge regarding the genotoxicity of STZ.