scholarly journals Metformin and l-glutamine ameliorate pancreatic damage induced by chronic nicotine exposure in adult male albino rats

2019 ◽  
Vol 7 (2) ◽  
pp. 44
Author(s):  
Eman Abdel-Mohsen Abdel-Aziz ◽  
Asmaa Y. A. Hussein ◽  
Heba A Elnoury

Nicotine is a major addictive component of tobacco and cigarettes. It is believed to play a major role in the development of many diseases of pancreas including induction of pancreatitis and pancreatic cancer. This study was designed to assess the ameliorative effect of metformin & L-glutamine administered either individually or in combination on pancreatic damage induced by chronic exposure to nicotine. Fifty-six adult male albino rats were divided into 7 weight matched groups of 8 animals per each group and treated once daily for a period of 10 weeks according to the following protocol; group I (normal control): left without intervention ; they were allowed to free access to balanced diet & distilled water for the end of the experiment, group II (metformin treated group; Met): metformin was administrated to normal rats at a dose of (150 mg/kg /day /orally); group III (glutamine group ; LG): in which L-glutamine was given to normal rats at a dose of 500 mg/kg by oral gavage); group IV (diseased non-treated group ;Nicotine) were injected subcutaneously with nicotine (1.5 mg/kg/day after day) to induce pancreatitis; group V (Nicotine +Met), VI (Nicotine +LG) &VII (Nicotine +Met + LG) were treated by (Nicotine +Met, Nicotine +LG & Nicotine +Met + LG respectively) by the same doses and routs described above. At the end of the experiment the following biochemical parameters were measured (fasting blood glucose, plasma insulin level, serum amylase and lipase level, tumor necrosis factor alpha (TNF-α), heat shock protein 70 (HSP70) & reduced glutathione; GSH) to investigate the protective effect of either or both drugs on pancreas. Additionally, histopathological evaluations of pancreatic tissues were assessed. The current study documented the damaging effect of nicotine on pancreas evidenced by significant increase of (blood glucose level due to decrease in plasma insulin level, serum lipase and amylase & TNF-α levels along with significant reduction of GSH in pancreatic tissue & heat shock protein -70. This was accompanied by histopathological alteration in pancreatic tissue. The previously mentioned parameters illustrate partial significant improvement in concomitant administration of individual or both metformin & L glutamine along with nicotine. In conclusion, co- supplementation of metformin and L glutamine documented to be anti-hyperglycemic, antioxidant and anti-inflammatory which can ameliorate the damaging effect of nicotine on pancreas. The combination use of both drugs produces more protective effect than each other alone.   

2019 ◽  
Vol 11 (12) ◽  
pp. 1155-1160
Author(s):  
Mohammed Al-Hariri ◽  
Tharwat Gamal Eldin ◽  
Mohammed Al-Harbi ◽  
Tarek Hashim ◽  
Rizwan Ahmad

This study was performed to investigate the hypoglycemic properties of Propolis and their possible role on pancreatic's tissue. Diabetes mellitus was induced in 45 adult male albino rats and the animals were divided into three groups; Negative control group received standard diet; Positive group diabetic untreated group; Propolis treated group supplemented with (0.3 g/Kg/day) for 2 weeks after the induction of diabetes by streptozotocin. At the end of the experiment, blood was collected from the abdominal aorta. A heparinized tube was used for collection of plasma for measurement of lipid peroxidation products, insulin, glucagon and fasting blood glucose. Pancreas were isolated and stained with hematoxylin and eosin (HE), histoimmunological and morphometric factors were studied. The results of this study showed that Propolis was able to reduce blood glucose significantly compared with the diabetic untreated group. Hypercellularity and density of B cells increased in pancreatic tissue, islets size and percent of B cells increased significantly in Propolis treated group which may signify regeneration of islets or B cells in Propolis treated rats. In the current study, we have demonstrated that, both structural and functional improvements of pancreas. Further researches are highly needed to clarify the specific molecular and cellular targets of various constituents of Propolis.


2008 ◽  
Vol 8 (2) ◽  
pp. 131-134 ◽  
Author(s):  
Muhidin Hamamdžić ◽  
Boris Hrabač ◽  
Amer Alić ◽  
Eva Pašić-Juhas ◽  
Aida Hodžić

The aim of the study was to explore the effect of lactate on insulin-stimulated glucose uptake in rats. Thirty Wistar rats, weighing 250 - 300 g. were arbitrarily divided into one of three groups (n =10): insulin (1 IU/kg) treated group, lactate (80 mg/kg), and insulin plus lactate treated groups. Blood glucose levels were measured in venous samples collected from the tail vein over 3 hour period after insulin or/and lactate administration in 30-minute intervals.To estimate the influence of lactate on insulin blood level, a total of 20 rats were divided into 4 groups (n = 5): saline, insulin, lactate, and insulin plus lactate treated group, respectively.Sixty minutes after the appropriate application of the same doses of insulin, lactate, and lactate plus insulin, as in the previous part of the experiment, plasma insulin and blood glucose levels were determined in blood samples drawn from the abdominal aorta. Lactate in combination with insulin, in comparison to insulin application alone, caused a dramatic increase in plasma insulin level (p<0,001) and more profound hypoglicaemia (p<0,001). The results of this investigation indicate that lactate application significantly increases the rate of glucose uptake from peripheral blood caused by exogenous insulin action. The possible involvement of lactate in the mechanism of enhanced glucose uptake due to insulin action after physical exercise is discussed.


Author(s):  
Tongtong Zhao ◽  
Kai Zhang ◽  
Yelei Zhang ◽  
Yating Yang ◽  
Xiaoshuai Ning ◽  
...  

Abstract Rationale and objective Clozapine (CLZ) is the most effective drug for treatment-resistant schizophrenia but is associated with many side effects, including glycometabolism disorders. Immunological mechanisms may be involved in the development of clozapine side effects. Research relating the immunomodulatory effects of clozapine and its early markers to clinically relevant adverse events is needed to reduce the harmful side effects of clozapine. This study aimed to investigate the role of proinflammatory cytokines in clozapine-associated glycometabolism disorders. Methods We measured the effect of a range of doses of clozapine on glycometabolism-related parameters and proinflammatory cytokines levels in mice peripheral blood. We also examined the differences between these indicators in the peripheral blood of clozapine-treated schizophrenia patients and healthy controls. Furthermore, we detected proinflammatory cytokines expression in mice pancreatic tissue. Results Following clozapine administration, glucagon significantly decreased in mouse serum, and proinflammatory cytokine IL-β levels markedly increased. Clozapine reliably increased proinflammatory cytokines (IL-1β, IL-6, and TNF-α) expression in murine pancreatic tissue. Compared with healthy controls, clozapine-treated patients’ BMI, blood glucose, and proinflammatory cytokines (IL-1β, IL-6, and TNF-α) increased significantly. In clozapine-treated patients, a higher clozapine daily dosage was associated with higher levels of the proinflammatory cytokines IL-1β and IL-6, and a significant positive correlation was observed between blood glucose levels and the proinflammatory cytokines IL-6 and TNF-α. Conclusion Findings from animal experiments and clinical trials have shown clear evidence that clozapine has a regulatory effect on immune-related proinflammatory cytokines and influences glycometabolism indicators.


2009 ◽  
Vol 28 (11) ◽  
pp. 679-687
Author(s):  
A. Ismail Khan ◽  
S. Yuvaraj ◽  
E. Suthagar ◽  
C. Parthasarathy ◽  
K. Balasubramanian

Many traditional treatments have been recommended in the alternative system of medicine for diabetes mellitus. However, the mode of action of most of the herbals used has not been defined. It has been reported that sex hormones are important regulators of insulin-mediated events in skeletal muscles. In view of this, a novel herbal preparation containing antidiabetic and aphrodisiac plants was used in the present study. Adult male albino rats were divided into following groups after induction of diabetes. Rats were given an intraperitoneal (i.p.) injection of streptozotocin (STZ), at a dose of 65 mg/kg body weight after overnight fasting, to induce diabetic state with blood glucose levels >250 mg/dL. Group 1—Control rats treated with single i.p. injection of vehicle, Group 2—Rats treated with polyherbal preparation (PHP; 500 mg/kg body weight by oral intubation, morning and evening for 30 days), Group 3—STZ-diabetic rats treated orally with equal volumes of vehicle (water) alone and Group 4—STZ-diabetic rats treated with PHP after 10 days of diabetic induction. STZ-diabetes decreased the body weight, serum insulin level and glucose oxidation in liver and skeletal muscles but increased the fasting blood glucose level. After polyherbal treatment, body weight and glucose oxidation were completely restored to control level while serum insulin level was restored partially and the glucose tolerance was significantly improved. There was a significant decrease in total haemoglobin (Hb) level of diabetic rats when compared to control but polyherbal treatment significantly improved the same. However, the other parameters studied (red blood cell [RBC], white blood corpuscle [WBC], packed cell volume [PCV], mean corpuscular volume [MCV] and mean corpuscular haemoglobin [MCH]) were unaltered. In conclusion, the anti-diabetic properties of PHP appear to be mediated through pancreatic β-cell regeneration, resulting in maintenance of optimal blood glucose and its oxidation in liver and skeletal muscles.


Author(s):  
Arsalan Uqaili ◽  
Samia Siddiqui ◽  
Roomi Aijaz ◽  
Yar Muhammad Nizammani ◽  
Navaid Kazi ◽  
...  

Objective: To determine the anti-hyperglycemic effects of interleukin-1 inhibitor (diacerein) in alloxan induced diabetic albino wistar rats. This experimental study was performed at the Department of Animal Husbandry and Veterinary Sciences, Sindh Agriculture University, Tando Jam within 6 months from April 2016 to September 2016. Total of 160 adult Albino Wistar Rats having an average of 200 to 300 grams body weights were selected. Animals were categorized into 4 groups as; Group A (n=15): Control rats – receive 0.9% normal saline as placebo Experimental Groups Group B (n=15): Experimental Control (Diabetic rats) - Alloxan50 mg/kg body weight intraperitoneal. Group C (n=15): Diabetic rats + Diacerein (30 mg/kg/day) orally daily. Group D (n=15): Diabetic rats + Diacerein (50 mg/kg/day) orally daily. Animals were kept and treated as per the NIH Guideline for Use and Care of Laboratory Animals. Diabetes mellitus was induced via a single intraperitoneal injection of 50 milligram/kg alloxan monohydrated dissolved in aseptic 0.9% saline. After 72 hours, blood specimens were taken from the caudal vein of the rats and glucose level>200 mg/dL was taken as diabetes. Experimental rats were given diacerein approximately 30 and 50 mg orally for 6 weeks. At the completion of experiment the body weight was measured of each animal by electronic measuring balance and blood sample was taken from each animal of all groups to assess the blood glucose level and HbA1c level. Data were recorded via self-made proforma and analysis was done by using SPSS version 20. Results: Average body weight of Diabetic control (Group B) was 193.33±22.50 grams, which was lower in contrast to Diacerein treated group C 202.47±25.70 grams and significantly lower as compared to Diacerein treated group D as  212.6±23.43 grams. A significant increase in blood glucose levels 182.07±10.63 mg/dl was noted in the Diabetic control (Group B) compared to Diacerein treated group C (110.13± 8.54 mg/dl) and group D (85.87±8.41 mg/dl) (P=0.001). HbA1c was markedly raised in the Group B- diabetic controls, while diacerein treated diabetic rats (groups C and D) showed a significant decrease in HbA1c (P=0.001). Conclusion: It was concluded that Diacerein achieves the Euglycemic state by reducing the levels of blood glucose and glycated hemoglobin (HbA1c) in Alloxan-Induced diabetes mellitus in Wistar Albino Rats.


2019 ◽  
Author(s):  
Randa H. Ainosah ◽  
Magda M. Hagras ◽  
Sameer Alharthi ◽  
Omar I. Saadah

Abstract Background: Cholestasis is a condition in which there is impairment of bile flow from the liver to the small bowel. It is a common complication of bacterial infection and sepsis. Treatment is usually directed towards the eradication of bacterial infection and consequences of sepsis. Ursodeoxycholic acid (UDCA) has been under investigation as a possible therapeutic option for the treatments of sepsis-associated cholestasis.Methods: Sixty male albino rats (weighing 100–150g) were subjected to daily doses of UDCA (100 mg/kg, p.o.) for 10 days before or after lipopolysaccharides (LPS) induction of cholestasis. Then, the following liver enzyme activity was assessed: plasma aspartate transferase (AST), plasma alkaline transferase (ALT), plasma alkaline phosphatase (ALP), total bilirubin (TBIL). Hepatocyte apoptosis and immunomodulatory activity were assessed by flow cytometric analysis. Plasma pro-inflammatory cytokines (TNF-, IL-1 and IL-4) were measured by ELISA. Liver histology changes were assessed by hematoxylin and eosin (H&E) staining.Results: Our results showed that LPS-induced cholestasis resulted in a significant rise in the TBIL and liver enzymes including GGT, ALP, AST, and hepatocytes death. UDCA improves serum liver chemistries and halts bile acid cytotoxicity when it was used either as a treatment or prevention, compared to the LPS group. Moreover, UDCA has immunomodulatory properties: the effect of UDCA on the percentage of natural killer (NK) cells did not change in either the treatment or prevention group when compared to LPS induced cholestasis. However, significant decrease in the CD3 has been found in the treatment group as compared to the LPS group, and an unexpected increase in the prevention group compared to the LPS treated group. UDCA failed to ameliorate the increase in plasma TNF-α concentration in the treatment group. On the other hand, UDCA caused reduction in plasma TNF-α in the prevention group. We also found significant reduction in the liver tissue apoptosis in the UDCA treated groups. Conclusion: Prophylactic treatment and treatment with UDCA appear to exert a beneficial effect against the damaging effect of hydrophobic bile acids by LPS-induced secretary failure. This involved multiple mechanisms of action.


2020 ◽  
Author(s):  
Hanom Husni Syam ◽  
Tono Djuwantono ◽  
Jusuf S. Effendi ◽  
Ponpon S. Idjradinata ◽  
Tita H. Madjid ◽  
...  

Abstract Background The leakage of hydrosalpinx fluid from the tube into the uterine cavity is likely to interfere with normal implantation. Hydrosalpinx fluids contain tumor necrosis factor-α (TNF-α), which induces caspase-9 signal transduction, leading to apoptosis. Endometrial cells inhibit apoptosis by synthesizing heat shock protein 70 (Hsp70). The TNF-α, caspase-9 and Hsp70 factors are closely related to apoptosis. In women with hydrosalpinx, the endometrial receptivity of embryonic implantation processes is low. Endometrial receptivity can be assessed by leukemia inhibitory factor (LIF). TNF-α, caspase-9 and Hsp70 expression plays an important role in endometrial receptivity disorders in women with hydrosalpinx.Materials and Methods These is an analytic observational, cross-sectional and categorical comparative study was conducted in 44 subjects with and without hydrosalpinx. The present study was performed in Dr. Hasan Sadikin Hospital, Grha Bunda-, Limijati-Maternity and Children Hospital (May-June 2017). Immunohistochemistry was performed with a cutoff based on the ROC. The Mann-Whitney analysis was performed on TNF-α, caspase-9, Hsp70 and LIF in both groups, whereas a correlation regression test was performed to observe the correlation among these protein.Results The present study used the histoscore as a tool to evaluate the expression of variable between study groups. The comparison of the histoscore for parameters between hydrosalpinx and non-hydrosalpinx subjects was TNF-α (12 vs 9; p<0,001), caspase-9 (12 vs 8,5; p<0,001), Hsp70 (6 vs 8; p<0,001), and LIF (9 vs 12; p<0,05), respectively.Conclusion The results showed a significant difference in TNF-α, caspase-9, Hsp70 and LIF (p <0.05) between hydrosalpinx and non-hydrosalpinx patients. Caspase-9 and Hsp70 are inter-connected and related to LIF as a marker in the endometrium receptivity by hydrosalpinx patients.


2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Tarek Kamal Abouzed ◽  
Eman Abd Elrahman Sherif ◽  
Mohamed El Sayed Barakat ◽  
Kadry Mohamed Sadek ◽  
Adil Aldhahrani ◽  
...  

Abstract Background Gentamicin (GM) is a low-cost, low-resistance antibiotic commonly used to treat gram-negative bacterial diseases. Cisplatin (Csp) is a platinum-derived anti-neoplastic agent. This experiment aimed to identify the early signs of gentamicin and cisplatin-induced nephrotoxicity in rats. Thirty Wistar rats were divided into three groups of 10: a control group, which received no treatment; a gentamicin group administered by a dose of (100 mg/kg, IP) for 7 consecutive days, and a cisplatin group was administered intraperitoneal in a dose of (1.5 mg/kg body weight) repeated twice a week for 3 weeks. Results Both experimental groups exhibited increased levels of creatinine, urea, and uric acid, with the cisplatin-treated group showing higher levels than the gentamicin group. Experimental groups also exhibited significantly increased Malondialdehyde (MDA), reduced glutathione (GSH), and glutathione peroxidase (GSH-Px) with more pronounced effects in the cisplatin-treated group. Further, both experimental groups exhibited significant up-regulation of Tumor Necrosis Factor α (TNF-α), caspase-3, and Bax and down regulation of Bcl-2. Conclusion These findings confirm the use of necrotic, apoptotic genes as early biomarkers in the detection of tubular kidney damage. Further, cisplatin was shown to have a greater nephrotoxic effect than gentamicin; therefore, its use should be constrained accordingly when co-administered with gentamicin.


1998 ◽  
Vol 66 (8) ◽  
pp. 3959-3963 ◽  
Author(s):  
Neide M. Silva ◽  
Ricardo T. Gazzinelli ◽  
Deise A. O. Silva ◽  
Eloisa A. V. Ferro ◽  
Lloyd H. Kasper ◽  
...  

ABSTRACT Stage conversion between bradyzoites and tachyzoites was investigated in C57BL/6 mice chronically infected with the ME-49 strain of Toxoplasma gondii. In order to promote bradyzoite-tachyzoite conversion, mice were treated in vivo with neutralizing doses of anti-gamma interferon (IFN-γ) or anti-tumor necrosis factor alpha (TNF-α) antibodies. Expression of parasite-specific antigens SAG-1, SAG-2, and heat shock protein 70 (Hsp-70) was visualized in the central nervous system by immunocytochemistry and measured by photometric assay. The immunosuppressive effect of anti-IFN-γ or anti-TNF-α treatment was immediate, leading to parasite stage conversion as indicated by the increased expression of tachyzoite-specific antigens (SAG-1 and SAG-2) and by rapid parasite replication. We also observed expression of high levels of Hsp-70 during a short period of conversion of bradyzoites to tachyzoites. Our data suggest that Hsp-70 may have an important role in the process of bradyzoite-tachyzoite conversion during the reactivation of chronic toxoplasmosis.


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