The induction of insulinomas by X-irradiation to the gastric region in Otsuka Long-Evans Tokushima Fatty rats

The X-ray induction of tumors was examined in five-week-old male Otsuka Long-Evans Tokushima Fatty (OLETF) rats, treated with two 10 Gy doses to the gastric region with a 3-day interval (total 20 Gy). After irradiation, the rats received the commercial diet MF and tap water and were maintained for up to 564 days. The mean serum glucose level in the X-irradiated group was significantly lower than that in the non-irradiated animals at the 18 month time point. The total tumor incidence was 27/30 (87.1%) in the treated rats (islet tumors, gastric tumors, sarcomas, seminomas, adrenal tumors, kidney tumors, papilloma, lymphomas and mammary tumors). Islet tumors, generally showed to be positive for insulin by immunohistochemistry, developed in 19 rats (63.3%), and were associated with low serum glucose. Since spontaneous tumors observed in 6/19 (31.6%) rats (sarcomas, kidney tumors, duodenum tumors, seminoma, adrenal tumor and squamous cell carcinoma) did not include any insulinomas, these are clearly induced by X-irradiation in OLETF rats

Review of the mechanism of cell death resulting from streptozotocin challenge in experimental animals, its practical use and potential risk to humans

AbstractStreptozotocin (STZ) (2-deoxy-2-({[methyl(nitroso)amino]carbonyl}amino)-β-D-glucopyranose) is a naturally occurring diabetogenic compound, produced by the soil bacterium streptomyces achromogenes, that exhibits broad spectrum of antibacterial properties. Streptozotocin functions as a DNA synthesis inhibitor in both bacterial and mammalian cells. In mammalian cells, the actual mechanism and metabolic targets of STZ toxicity that results in cell death is not known. This review identifies four key areas that explain the mechanism of the cytotoxicity of STZ in mammalian cell lines, investigates the practical aspects of using STZ in experimental animals and the potential risks of its exposure to human health.</jats:p

Role of Nicotinamide in DNA Damage, Mutagenesis, and DNA Repair

Nicotinamide is a water-soluble amide form of niacin (nicotinic acid or vitamin B3). Both niacin and nicotinamide are widely available in plant and animal foods, and niacin can also be endogenously synthesized in the liver from dietary tryptophan. Nicotinamide is also commercially available in vitamin supplements and in a range of cosmetic, hair, and skin preparations. Nicotinamide is the primary precursor of nicotinamide adenine dinucleotide (NAD+), an essential coenzyme in ATP production and the sole substrate of the nuclear enzyme poly-ADP-ribose polymerase-1 (PARP-1). Numerous in vitro and in vivo studies have clearly shown that PARP-1 and NAD+ status influence cellular responses to genotoxicity which can lead to mutagenesis and cancer formation. This paper will examine the role of nicotinamide in the protection from carcinogenesis, DNA repair, and maintenance of genomic stability

Apoptosis and Medicine

This book looks at the latest research studies on apoptosis in medicine. It is divided into three sections for convenient and easy reading. The first section which comprises two chapters is an introduction of the subject of apoptosis to the uninitiated. The second section which comprises a single solitary chapter looks at apoptosis in normal physiology during bone resorption under mechanical stress. The third and the final section reviews apoptosis in a number of pathological conditions with an emphasis on cancer

A COMPARATIVE STUDY OF THE ANTI-OXIDATIVE AND ANTI-DIABETIC POTENTIAL OF IN VITRO AND IN VIVO ROOT AND LEAF EXTRACTS OF WITHANIA SOMNIFERA ON STREPTOZOTOCIN INDUCED DIABETIC RATS

Objective: The present investigation explores the possibilities of using the in vitro and in vivo root and leaf extracts of Withania somnifera for anti-diabetic and anti-hyperlipidaemic effects on streptozotocin-induced diabetic rats.Methods: In vitro shoot cultures of Withania somnifera were raised by the axillary proliferation in nodal explants from a garden grown plant using Murashige and Skoog medium then in vitro raised roots and shoots were used for the anti-hyperglycemic and anti-hyperlipidaemic experiment. After 72 h of STZ administration, the fasting blood glucose levels were measured and the rats showing FBG level&gt;220 mg/dl were considered to be diabetic and were used for the hyperglycemic study. In vitro and in vivo methanolic root and leaf extracts were orally administered daily to diabetic rats for eight weeks. After the treatment period, blood glucose and serum enzymes like aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total cholesterol, triglycerides, HDL-c high density lipoprotein-bound cholesterol, LDL-c low density lipoprotein-bound cholesterol, LDH, serum protein level, total phenolics and anti-oxidative analysis (DPPH and FRAP) were determined.Results: The levels of blood glucose, AST, ALT, ALP, LDH, HDL-c significantly increased by the use of in vitro methanolic root extracts compared to normal control rats. However, remarkable loss of total protein, albumin, albumin: globulin (A: G) ratio was reported in streptozotocin-induced diabetic rats by using in vitro root extracts. Methanolic in vitro root extract at the dose levels of 300 mg/kg body weight produced a significant decrease in fasting blood glucose (FBG) level by 102.65 with respect to initial fasting blood glucose level after 30 d of the treatment. In vitro root extract demonstrated highest DPPH and FRAP free radical scavenging activity, i.e. 86.55±1.77 and 48.87±2.55 than other extracts.Conclusion: It may be concluded that methanolic in vitro root extract W. somnifera at the dose (300 mg/kg) has more potent anti-hyperglycaemic activity than the other in vitro and in vivo extracts of leaf and root on streptozotocin induced diabetic rats and was also found to be similar in effect to that of the standard drug ‘Glibenclamide'

Nonhuman Primate Models of Type 1 Diabetes Mellitus for Islet Transplantation

Islet transplantation is an attractive treatment of type 1 diabetes mellitus (T1DM). Animal models of diabetes mellitus (DM) contribute a lot to the experimental studies of islet transplantation and to evaluations of isolated islet grafts for future clinical applications. Diabetic nonhuman primates (NHPs) represent the suitable models of DMs to better evaluate the effectiveness of islet transplantation, to assess new strategies for controlling blood glucose (BG), relieving immune rejection, or prolonging islet survival, and eventually to translate the preclinical data into tangible clinical practice. This review introduces some NHP models of DM, clarifies why and how the models should be used, and elucidates the usefulness and limitations of the models in islet transplantation

Evaluation on Anti-Diabetic Effect of Ethanolic Extract of Whole Plant of Nymphaea Pubescens on Streptozotocin Induced Diabetes in Wistar Rats

The present study were Management of Diabetes mellitus is a global problem, successful treatment is very important for preventing or at least delaying the onset of long term diabetic complications like diabetic neuropathy, nephropathy, retinopathy, erectile dysfunction, hypertension and injury caused by ischaemic and reperfusion. Through nature in the form of herbal medicines or drugs with very minimal adverse effects are preferred when compared to the available synthetic drugs to treat such chronic disease and disorders. Herbal drugs as therapeutic agents are a nature’s boon when compared to the severe adverse effects of the allopathic medical practice for diabetes, despite the fact that the search for a complete and permanent cure for the disease is being pursued uncompromisingly by eluding physicians and researchers. These herbal remedies which exemplifies the process of symbiosis still remains unfamiliar up to data technical advances, which has fashioned a marvelous scope for folk lore or traditional medicines .It is supposed that the tradition medicines used for the treatment of diabetes mellitus satisfy the sequence of complication of the disease. Even though, the traditional medicinal plants are used to cure the disease from human origin, scientific validation of such medicinal plants are necessary and also a scientific research to prove its pharmacological and therapeutic efficacy is became vital. Nymphaea pubescens willd is having the anti-diabetic activity. As per the literature review still no anti-diabetic activity has been reported on this whole plant. Hence, this study has been taken to explore the anti-diabetic potential of Nymphaea pubescens willd on streptozotocin induced diabetes in wistar albino rats.DISCUSSION AND CONCLUSION:The ethanolic extract from whole plant of Nymphaea Pubescens were subjected to preliminary phytochemical analysis which shown presence of flavonoids, alkaloids, tannins, proteins, steroids and phenol with absence of saponins and anthroquinones. Acute oral toxicity studies of EENP did not produce any mortality or signs of toxicity at the dose of 2000 mg/kg b.w/p.o, in experimental rats. The anti-hyperglycemic effects of the plants is due to their ability to restore the function of pancreatic tissues by causing an increase in insulin output or inhibit the intestinal absorption of glucose or to the facilitation of metabolites in insulin dependent processes. Hence, treatment with herbal drugs has an effect on protecting b cells and smoothing out fluctuation in glucose levels72 The present study evalulation of anti-diabetic activity of whole plant of Nymphaea pubescens STZ induced diabetic rats. Experimental induction of hyperglycemia with STZ is associated with the characteristic loss of body weight which is due to loss or degradation of structural proteins it leads to increased muscle wasting and due to loss of tissue protein, as the structural proteins are known to contribute to body weight. Diabetic rats treated with glibenclamide and EENP showed increased body weight when compared to untreated diabetic animals. It may be due to increased insulin secretion and glycemic control of EENP. Reduced glucose transport or absorption from the gut, extra pancreatic action probably by stimulation of glucose utilization in peripheral tissues, increase in glycogenic or glycolytic enzyme activities in peripheral tissues, decrease in the secretion of counter-regulatory hormones like glucagon, growth hormones are the possible mechanisms involved with suppressing blood glucose levels. The glibenclamide, stimulating insulin secretion from pancreatic β cells principally by inhibiting ATP sensitive KATP channels in the plasma membrane and decreases the blood glucose level73. Blood glucose level decreased significantly in glibenclamide and EENP treated diabetic rats and the histopathology of pancreas showed normal islets in pancreas with normal anatomy compared with normal rats which may be due to the anti-diabetic activity. Hyperglycaemia is accompanied with dyslipidemia under normal circumstances; insulin activates the enzyme lipoprotein lipase, which hydrolyses triglycerides. However, in diabetic state lipoprotein lipase is not activated due to insulin deficiency, resulting in hyper triglyceridemia, and insulin deficiency is also associated with hyper cholesterolemia due to metabolic abnormalities. The dyslipidemia is characterized by increase in TC, LDL, VLDL, TG and fall in HDL which is observed in STZ induced diabetic rats74. The diabetic rats treated with glibenclamide and EENP showed reduced severity of dyslipidemia with decrease in TC, LDL, VLDL, TG and increase in HDL. Both SGOT and SGPT enzyme levels get elevated during liver damage which is more in diabetic rats75. The diabetic rats treated with glibenclamide and EENP reduced the SGOT and SGPT level. The liver histopathology of STZ induced diabetic rats showed centrilobular necrosis accompanied by fatty changes and ballooning degeneration in the hepatocytes treatment with EENP reversed in diabetic rats treated with glibenclamide and EENP which indicates that the liver damage is reduced in EENP treated group. The diabetic hyperglycaemia induces elevation of the serum levels of creatinine which are significant markers of renal dysfunction, The treatment of EENP in rats showed marked decrease in serum creatinine levels in diabetic animals