scholarly journals Paradoxical refractoriness developing with the allogeneic transfer of splenic lymphocyte total RNA from animals with treated alloxan diabetes to animals with untreated diabetes

Author(s):  
Н.М. Геворкян ◽  
Н.В. Тишевская ◽  
А.Г. Бабаева

Ранее нами было показано, что препараты аллогенной суммарной РНК, выделенной из лимфоидных и стволовых клеток здоровых животных, вызывают нормализацию уровня глюкозы крови у крыс со стойким аллоксановым сахарным диабетом. Цель исследования -- выяснение влияния суммарной РНК лимфоцитов селезенки крыс, ранее перенесших стойкий аллоксановый диабет, на особенности течения эксперименального аллоксанового диабета у животных. Методика. Эксперимент выполнен на 35 белых беспородных крысах-самках массой 250-280 г: 5 интактных животных, 20 - с экспериментальным аллоксановым сахарным диабетом и 10 животных, ранее перенесших стойкий аллоксановый диабет, у которых уровень глюкозы крови был полностью нормализован введением суммарных РНК клеток костного мозга, селезенки и поджелудочной железы. Диабет у этих животных моделировали однократным подкожным введением полного адъюванта Фрейнда (0,5 мл на крысу) и последующим подкожным введением аллоксана тригидрата в дозе 200 мг/кг. Достигнутая нормогликемия у животных подтверждалась в течение последующих 60 сут. Из селезенок и костного мозга этих животных методом фенол-хлороформной экстракции была выделена суммарная РНК. На 20 крысах с экспериментальным аллоксановым сахарным диабетом изучали эффекты однократного внутрибрюшинного введения полученной суммарной РНК (15 мкг/100 г массы тела животного). Результаты. Обнаружено, что при введении суммарной РНК селезенки крыс, ранее перенесших аллоксановый диабет, животным с аллоксановым диабетом у последних развивалась стойкая и длительная рефрактерность к лечению терапевтическими препаратами РНК. Заключение. 1. Выявлен феномен повышенной чувствительности крыс с аллоксановым диабетом к действию суммарной РНК селезенки животных, ранее перенесших аллоксановый диабет. 2. Предполагаемой причиной рефрактерности является клональный компонент суммарной РНК CD8+ Т-лимфоцитов памяти из селезенки животных, ранее перенесших аллоксановый диабет. 3. Предполагается наличие механизма адресного взаимодействия отдельных компонентов суммарной РНК селезенки крыс, ранее перенесших аллоксановый диабет, с их лимфоцитами-мишенями в организме реципиентов с аллоксановым диабетом. Introduction. Earlier we have shown that preparations of allogenic total RNA from lymphoid and stem cells of healthy animals contribute to normalization of blood glucose levels in white outbred rats with persistent alloxan-induced diabetes mellitus. The aim of this study was to find out whether allogenic total RNA isolated from the spleen of rats treated for alloxan diabetes affects its course, as determined by changes in blood glucose, in animals with persistent alloxan diabetes. Methods. Experiments were performed on 35 white outbred female rats weighing 250-280 g. Rats were divided into intact animals (n=5), rats with experimental alloxan diabetes mellitus (n=20), and rats after persistent alloxan diabetes (n=10) whose blood glucose level had been completely normalized by administrating total RNA of bone marrow, splenic, and pancreatic cells (post-diabetes group). Diabetes mellitus was modeled with a single subcutaneous (s.c.) injection of complete Freund’s adjuvant (0.5 ml) followed by a s.c. injection of alloxan trihydrate (200 mg/kg). Achievement of normoglycemia in animals of the post-diabetes group was confirmed over the next 60 days. Then total RNA was isolated from their spleen and bone marrow by phenol-chloroform extraction, and the effect of a single intraperitoneal injection of total RNA (15 μg/100 g body weight) was studied. Results. Administration of splenic total RNA from rats previously treated for alloxan diabetes to animals with alloxan diabetes resulted in development of stable and prolonged refractoriness of diabetic rats to the treatment with therapeutic RNA preparations [11]. Conclusions. This study discovered a phenomenon of hypersensitivity of rats with alloxan diabetes to the diabetogenic effect of total RNA from animals that had previously had alloxan diabetes. Apparently, this refractoriness was caused by the clonal component of the total RNA of CD8 + T memory lymphocytes from the spleen of post-diabetes animals. A mechanism is proposed for the interaction between individual components of splenic total RNA from post-diabetes rats and their target lymphocytes in recipients with alloxan diabetes.

Author(s):  
Н.М. Геворкян ◽  
Н.В. Тишевская ◽  
А.Г. Бабаева

Введение. Как было нами показано ранее, препараты аллогенных суммарных РНК лимфоидных и стволовых клеток способствуют нормализации уровня глюкозы в крови белых беспородных крыс со стойким аллоксановым диабетом. Цель исследования - оценка влияния суммарной РНК, выделенной из селезенки крыс с аллоксановым диабетом, на уровень глюкозы в крови интактных крыс и животных, перенесших стойкий аллоксановый диабет. Методика. Эксперимент выполнен на 34 белых беспородных крысах-самках массой 250-280 г.: 12 интактных животных составили «интактный контроль». У 22 животных моделировали аллоксановый диабет путем однократного подкожного (п/к) введения полного адъюванта Фрейнда (0,5 мл) и последующего подкожного введения аллоксана тригидрата (200 мг/кг) - группа «алоксановый диабет». Селезенка 10 крыс группы «аллоксановый диабет» была использована для получения суммарной РНК. У 12 крыс группы «аллоксановый диабет» уровень глюкозы в крови был стабильно нормализован введением суммарной РНК клеток костного мозга, селезенки и поджелудочной железы - группа «перенесшая диабет». На 45-е сут эксперимента 12 крыс группы «интактный контроль» и 12 крыс группы «перенесшей диабет» использованы в новом опыте (по протоколу «2-й этап работы»). У 6 животных группы «интактный контроль» (впервые) и у 6 животных группы «перенесший диабет» (повторно) моделировали аллоксановый диабет путем подкожного введения аллоксана в дозе 100 мг/кг. Оставшимся 6-ти животным группы «интактный контроль» и 6-ти животным группы «перенесших диабет» вводили внутрибрюшинно суммарную РНК (15 мкг/100 г веса тела), выделенную из селезенок 10 крыс группы «аллоксановый диабет. Результаты. Показано, что исследуемая суммарная РНК в дозе 15 мкг/100 г массы тела вызывала гипергликемию у всех подопытных животных, сравнимую с действием 600-700-кратной дозы самого аллоксана, при этом крысы, ранее перенесшие диабет, реагировали значимо сильнее. Повторный контакт с аллоксаном у крыс, перенесших ранее диабет, так же вызывал значимо более выраженную гипергликемию, чем реакция на аллоксан у интактных крыс. Заключение. Выявлен феномен диабетогенного действия исследуемой суммарной РНК, а также повышенную чувствительность животных, ранее перенесших аллоксановый диабет, к повторному действию повреждающего агента. Полученные эффекты свидетельствуют о принципиальной возможности использовать суммарную РНК лимфоидных клеток для создания моделей заболеваний человека и разработку новых подходов в области персонифицированной медицины. Introduction. As we have shown earlier, preparations of allogenic total RNA from lymphoid and stem cells contribute to normalization of blood glucose levels in white outbred rats with persistent alloxan-induced diabetes. The aim of this study was to evaluate the effect of total RNA from the spleen of rats with alloxan diabetes on blood glucose of intact and post-alloxan diabetic animals. Method. Experiments were performed on 34 white outbred female rats weighing 250-280 g. Rats were divided into intact animals (n=12) and rats with experimental alloxan diabetes mellitus (n=22). Diabetes mellitus was modeled by a single subcutaneous (s.c.) injection of complete Freund’s adjuvant (0.5 ml) followed by a s.c. injection of alloxan trihydrate (200 mg/kg). Spleens from 10 rats with alloxan diabetes were used for obtaining total RNA. In the remaining 12 rats with alloxan diabetes, the level of blood glucose was completely normalized by administration of total RNA from the bone marrow, spleen, and pancreas (post-diabetes group). On day 45 of this experiment, 12 intact rats and 12 post-diabetes rats were used for a new experiment (second stage protocol). Alloxan diabetes was induced in 6 intact rats (for the first time) and 6 post-diabetes rats (for the second time) by a s.c injection of alloxan 100 mg/kg. The remaining 6 rats of the intact control group and 6 rats of the post-diabetes group received an injection of total RNA (15 μg/100 g body weight, i.p.). Results. Administration of total RNA (15 μg/100 g body weight) induced hyperglycemia in all experimental animals, which was comparable with the effect of a 600-700-fold dose of alloxan. Rats that had previously had diabetes responded to the total RNA significantly stronger. Likewise, a repeated exposure to alloxan of post-diabetes rats induced significantly more pronounced hyperglycemia than the response to alloxan of intact rats. Conclusions. This study discovered a phenomenon of hypersensitivity to repeated exposure to alloxan and to the diabetogenic effect of total RNA in animals that had previously had alloxan diabetes. This effect suggests a possibility of using the total RNA of lymphoid cells to create animal models of human diseases and to develop new approaches in personalized medicine.


1997 ◽  
Vol 56 (3) ◽  
pp. 209-213 ◽  
Author(s):  
Claudio Coimbra Teixeira ◽  
Luciano Pilla Pinto ◽  
Felix Henrique Paim Kessler ◽  
Lia Knijnik ◽  
Cristiano Pilla Pinto ◽  
...  

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Shih-Yi Kao ◽  
Jia-Fwu Shyu ◽  
Hwai-Shi Wang ◽  
Chi-Hung Lin ◽  
Cheng-Hsi Su ◽  
...  

Background. Type 1 diabetes mellitus results from autoimmune destruction ofβ-cells. Insulin-producing cells (IPCs) differentiated from mesenchymal stem cells (MSCs) in human tissues decrease blood glucose levels and improve survival in diabetic rats. We compared the differential ability and the curative effect of IPCs from three types of human tissue to determine the ideal source of cell therapy for diabetes.Methods. We induced MSCs from Wharton’s jelly (WJ), bone marrow (BM), and surgically resected pancreatic tissue to differentiate into IPCs. Thein vitrodifferential function of these IPCs was compared by insulin-to-DNA ratios and C-peptide levels after glucose challenge.In vivocurative effects of IPCs transplanted into diabetic rats were monitored by weekly blood glucose measurement.Results. WJ-MSCs showed better proliferation and differentiation potential than pancreatic MSCs and BM-MSCs.In vivo, WJ-IPCs significantly reduced blood glucose levels at first week after transplantation and maintained significant decrease till week 8. BM-IPCs reduced blood glucose levels at first week but gradually increased since week 3. In resected pancreas-IPCs group, blood glucose levels were significantly reduced till two weeks after transplantation and gradually increased since week 4.Conclusion. WJ-MSCs are the most promising stem cell source forβ-cell regeneration in diabetes treatment.


2021 ◽  
Vol 67 (2) ◽  
pp. 9-16
Author(s):  
Mgs Irsan Saleh ◽  
Rachmat Hidayat ◽  
Geri Febriyanto ◽  
Nita Parisa

Summary Introduction: Karamunting (Rhodomyrtus tomentosa) is Indonesian native plant that contains high anti-oxidant compounds with the potential to suppress oxidative stress activity in cells. This study is the first research to specifically explore the role of the karamunting fraction in protecting kidney damage due to the formation of AGEs in the renal glomerulus in diabetes mellitus. Objective: This study aims to assess the impact of karamunting on blood glucose profile, HbA1c, insulin profile and kidney condition (AGEs expression, TNF-α and kidney histology) in diabetic rats. Methods: The karamunting extraction process was carried out by maceration with ethanol. Induction of diabetes mellitus was carried out using streptozotocin. Thirty male rats (Rattus norvegicus), Wistar strain weighing between 200–250 grams were the subject in this study. HbA1c, insulin, TNF-α, AGEs levels were evaluated in the kidney tissue. Histological assessment of the kidney was carried out. Results: Karamunting can improve blood glucose levels in diabetic rats. This improvement in blood glucose levels causes an improvement in the level of HbA1c. Administration of karamunting fraction can prevent AGEs deposition in renal tissue, which in turn will inhibits the inflammation and prevents further damage of kidneys. Conclusion: Karamunting fraction can improve blood glucose regulation so that it can prevent further damage and complications of kidney organs in diabetic rats.


Author(s):  
Mugdha Rajeeva Padhye ◽  
Sangita Devrao Jogdand

Background: Diabetes mellitus is a chronic metabolic disorder of glucose metabolism characterised by hyperglycaemia. Long standing diabetes mellitus leads to various complications affecting multiple organ systems. Management of diabetes mellitus includes lifestyle modification and pharmacotherapy. Pharmacotherapy of diabetes mellitus includes a wide variety of drugs that help in achieving adequate glycaemic control. Anti-diabetic medications are however associated with several adverse effects. Phytochemicals are being used extensively for the treatment of various diseases. Use of phytochemicals would minimize adverse effects due to various anti-diabetic drugs and improve patient compliance. In the present study, authors studied the effect of turmeric on alloxan induced diabetes mellitus in albino rats.Methods: Albino Wistar rats of either sex weighing 180 - 250grams were utilized for the present study. Diabetes mellitus was induced by intraperitoneal administration of alloxan. Ethanolic extract of turmeric was administered to diabetic rats daily orally for duration of 28 days. Blood glucose levels were monitored using glucometer before and after intervention with turmeric.Results: Statistically significant reduction in mean blood glucose levels (p value <0.05) was seen after intervention with turmeric in diabetic rats. There was a significant reduction in mean blood glucose levels.Conclusions: Ethanolic extract of turmeric showed antihyperglycemic effect in diabetic rats.


1988 ◽  
Vol 16 (4) ◽  
pp. 300-304 ◽  
Author(s):  
T. Katoh ◽  
Y. Maeda ◽  
H. Yamato ◽  
T. Hirai ◽  
T. Fujii ◽  
...  

The results are presented of a controlled study in male Wistar rats into the effects of 24 R,25-dihydroxyvitamin D3 on blood glucose levels, bone calcium content and ADP-induced platelet aggregation in streptozocin-induced diabetes mellitus. Blood glucose levels were shown to be decreased by 10 μg/kg 24 R,25-dihydroxyvitamin D3. The reduced bone calcium content associated with diabetes mellitus was returned to normal levels with both 1 and 10 μg/kg 24 R,25-dihydroxyvitamin D3. It was also shown to exhibit dose-dependent anti-platelet activity. The data suggest that 24 R,25-dihydroxyvitamin D3 might have potential as a mild therapeutic agent in the treatment of osteoporosis and platelet hyperactivity associated with diabetes mellitus.


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
S. A. Sheweita ◽  
S. Mashaly ◽  
A. A. Newairy ◽  
H. M. Abdou ◽  
S. M. Eweda

Alhagi maurorum(camel thorn plant) is a promising medicinal plant due to the presence of flavonoids and phenolic compounds as major contents of its constituents. No previous study has been conducted before onA. maurorum extractsas an antioxidative stress and/or antidiabetic herb in STZ-induced DM in rats. Therefore, four groups of rats were allocated as control (C), STZ-induced DM (D), and STZ-induced DM supplemented with 300 mg/kg BW of either aqueous extract (WE) or ethanolic extract (EE) ofA. maurorum. The plasma levels of glucose, TG, TC, LDL-C and VLDL-C, MDA, and bilirubin and the activities of transaminases and GR were significantly increased in the diabetic group. Also, diabetic rats showed severe glucose intolerance and histopathological changes in their livers. In addition, levels of insulin, total proteins, GSH, and HDL-C and the activities of SOD, GPx, and GST were significantly decreased in the diabetic rats compared to those of the control group. The ingestion ofA. maurorumextracts lowered the blood glucose levels during the OGTT compared to the diabetic rats and restored all tested parameters to their normal levels with the exception of insulin level that could not be restored. It is concluded thatA. maurorumextracts decreased elevated blood glucose levels and hyperlipidemia and suppressed oxidative stress caused by diabetes mellitus in rats.


Author(s):  
Archita C. Joshi ◽  
Chetna R. Patel ◽  
Naresh D. Kantharia

Background: Diabetes mellitus is known to cause cognitive impairment that can be possibly attributed to deficient levels of leptin in diabetic animals. This study was undertaken to study the effect of administration of leptin on spatial learning, memory and blood glucose levels in diabetic rats.Methods: Rats were divided into three groups. The first group was the control group. Diabetes was induced in groups 2 and 3 by streptozotocin (STZ) injection (60 mg/kg) intraperitoneally. Group 2 received saline while group 3 received leptin (0.1 mg/kg) subcutaneously for 10 days from 4th day of STZ administration. Behavioural assessment was done in T maze after 21 days of the last injection of leptin. Blood glucose levels were also analysed.Results: The number of correct arm entries decreased while time spent being immobile and time spent to reach the correct arm increased in the diabetic group when compared to the control group and correct arm entries increased while time spent immobile and time spent to reach the correct arm decreased with leptin treatment when compared to the diabetic control rats. Blood glucose levels increased in the diabetic rats while leptin administration reduced blood glucose levels in the group 3.Conclusions: Our study suggests that leptin can improve learning and memory while also producing a slight reduction in the blood glucose levels in diabetic rats.


2019 ◽  
Vol 88 (3) ◽  
pp. 349-354 ◽  
Author(s):  
Rahil Parsamehr ◽  
Somayeh Bohlouli

Diabetes mellitus is a metabolic disease characterized by elevated blood glucose levels. Medicinal plant Ferulago angulata has anti-oxidant properties. The aim of the present research was to evaluate the effect of a hydroalcoholic extract of F. angulata on the blood glucose level and liver enzyme activity in diabetic male rats. Forty-eight male rats were randomly divided into eight groups, including normal and diabetic groups. Diabetes was induced by a single intraperitoneal injection of streptozotocin at 40 mg·kg-1 body weight. Rats were treated with an intraperitoneal injection of the extract for three weeks. At the end of the experimental period, fasting blood samples were collected, and blood glucose and liver enzyme activity were measured. This study demonstrated that serum glucose levels in diabetic groups treated with F. angulata were significantly lower than those in diabetic rats (P < 0.001). Alanine aminotransferase levels in diabetic rats treated with F. angulata were significantly decreased compared to diabetic rats (P < 0.001). Aspartate aminotransferase levels in diabetic rats treated with 200 and 400 mg·kg-1 F. angulata were significantly decreased compared to diabetic rats (P < 0.001). No significant differences were observed in the serum levels of blood glucose and liver enzymes in the normal group treated with different doses of the extract. These results show that the hydroalcoholic extract of F. angulata might be effective in the treatment of diabetes and consequently alleviate the liver damage caused by streptozotocin-induced diabetes mellitus. This effect might be due to the presence of flavonoids and their antioxidant features.


2015 ◽  
Vol 34 (9) ◽  
pp. 859-868 ◽  
Author(s):  
H Elbe ◽  
M Esrefoglu ◽  
N Vardi ◽  
E Taslidere ◽  
E Ozerol ◽  
...  

In this study, effects of melatonin, quercetin and resveratrol on hepatocellular injury in streptozotocin (STZ)-induced experimental diabetes were aimed to be investigated by histological and biochemical methods. Thirty-five male Wistar albino rats were divided into five groups, namely, control, diabetes (STZ 45 mg/kg/single dose/intraperitoneally (ip)), diabetes + melatonin (10 mg/kg/30 days/ip), diabetes + quercetin (25 mg/kg/30 days/ip) and diabetes + resveratrol (10 mg/kg/30 days/ip). Initial and final blood glucose levels and body weights (BWs) were measured. At the end of the experimentation, following routine tissue processing procedure, sections were stained with haematoxylin–eosin (H-E), periodic acid Schiff and Masson’s trichrome. Tissue malondialdehyde (MDA) and glutathione (GSH) levels and superoxide dismutase (SOD) and catalase (CAT) activities were examined. The diabetic rats had significantly higher blood glucose levels than those of control rats ( p = 0.0001). Mean BWs of diabetic rats were significantly decreased when compared with the control rats ( p = 0.0013). Histopathological alterations including cellular glycogen depletion, congestion, sinusoidal dilatation, inflammation and fibrosis were detected in diabetes group. On the other hand, histopathological changes markedly reduced in all of the treatment groups ( p = 0.001). Mean tissue MDA level was increased but mean tissue CAT and SOD activities and GSH levels were decreased in the diabetes group. Melatonin, quercetin and resveratrol administered diabetic rats showed an increase in CAT activities and GSH levels and a decrease in MDA levels ( p < 0.05, for all). Melatonin, quercetin and resveratrol administrations markedly reduced hepatocellular injury in STZ-induced experimental diabetes.


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