Dose-dependent and time-dependent metabolic, hemodynamic, and redox disturbances in dexamethasone-treated Wistar rats

Author(s):  
Elvine P. Nguelefack-Mbuyo ◽  
Fernande P. Peyembouo ◽  
Christian K. Fofié ◽  
Télesphore B. Nguelefack

Abstract Objectives Dexamethasone is used experimentally to induce insulin resistance and type 2 diabetes. However, data concerning the dose, the duration of treatment, and the associated comorbidities are inconsistent. The aim of this study was to compare the effects of different doses of dexamethasone and the duration of treatment necessary for the development of a model of insulin resistance that mimics the clinical condition with the associated comorbidities. Methods Dexamethasone was administered intramuscularly to male Wistar rats, at doses of 500 and 1,000 µg/kg/day for the subchronic treatment (eight consecutive days) and at doses of 5, 25, 50, and 100 µg/kg/day in chronic treatment (28 consecutive days). Effects on body weight, metabolism, hemodynamics, renal function, and redox status were evaluated. Results Both treatments induced a progressive body weight loss that was drastic in subchronic treatment, improved glucose tolerance without affecting fasting glycemia. Doses of 1,000 and 100 µg/kg were associated with hypertriglyceridemia, hypertension, and increased heart rate, cardiac and renal hypertrophy. Increased creatinemia associated with reduced creatinuria were observed in sub-chronic treatment while increased proteinuria and reduced creatinuria were noticed in chronic treatment. 1,000 µg/kg dexamethasone caused an increase in hepatic, and renal malondialdehyde (MDA) and glutathione (GSH) coupled with a reduction in catalase activity. The dose of 100 µg/kg induced a rise in GSH and catalase activity but reduced MDA levels in the kidney. Conclusions Doses of 1,000 µg/kg for subchronic and 100 µg/kg for chronic treatment exhibited similar effects and are the best doses to respective time frames to induce the model.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Paula L. Cruz ◽  
Ivana C. Moraes-Silva ◽  
Amanda A. Ribeiro ◽  
Jacqueline F. Machi ◽  
Marcelo Dantas Tavares de Melo ◽  
...  

Abstract Background To evaluate the effect of nicotinamide prior to streptozotocin-induced (STZ) diabetes in baroreflex sensitivity and cardiovascular autonomic modulation, and its association with hemodynamics and metabolic parameters. Methods Methods: Male Wistar rats were divided into control (Cont) and STZ-induced diabetes (Diab). Half of the rats from each group received a single dose of nicotinamide (100 mg/Kg) before STZ injection (Cont+NicA and Diab+NicA). All groups were followed-up for 5 weeks. Results Body weight loss of more than 40% was observed in Diab throughout the period (Diab: 271.00 ± 12.74 g; Diab+NicA: 344.62 ± 17.82). Increased glycemia was seen in Diab rats (541.28 ± 18.68 mg/dl) while Diab+NicA group had a slight decrease (440.87 ± 20.96 mg/dl). However, insulin resistance was observed only in Diab. In relation to Cont, heart rate, mean blood pressure and diastolic function were reduced when compared to Diab, together with parasympathetic modulation and baroreflex sensitivity. All of these parameters were improved in Diab+NicA when compared to Diab. Improved baroreflex sensitivity and parasympathetic modulation were correlated with glycemia, insulin resistance, and body weight mass. Additionally, Diab+NicA group increased survival rate. Conclusions Results suggest that the association of nicotinamide in STZ-induced diabetic rats prevents most of the expected derangements mainly by preserving parasympathetic and baroreflex parameters.


2019 ◽  
Vol 31 (3) ◽  
pp. 208
Author(s):  
Dian Widya Damaiyanti ◽  
Pratiwi Soesilowati ◽  
Ira Arundina ◽  
Rima Parwati Sari

Introduction: Gold sea cucumber (Stichopus hermanii) is a marine organism that contains omega-3 and glycosaminoglycan for enhancing collagen needed in the healing process. This study was aimed to determine the effectiveness of gold sea cucumber extracts in accelerating the healing process of oral traumatic ulcer in Wistar rats, in terms of the correlation between collagen type I expression, ulcer diameter, and body weight loss. Methods: Twenty Wistar rats (Rattus norvegicus) was divided into four groups and treated with gold sea cucumber extracts with the concentration of 80%, 40%, and 20% in the form of 0.1 ml gel daily. The negative control group received no treatment. Ulceration of the lower lip of labial mucosa was induced by a burnisher. The animals were observed for 7 days, during which they were weighed and the ulcers diameter was measured. The rats were then sacrificed after 7 days of treatment. Histometric analysis of collagen type I expression was also performed. Data obtained were analysed for differences between the group with one-way ANOVA test and the correlation was analysed with the Pearson test. Results: The significant differences (p < 0.05) between treatment groups was found in the ulcer diameters and the collagen type I expression. The most decreased ulcer diameter and the highest collagen type I expression detected in the group of treatment with a concentration of 80% — no significant differences found in the weight loss between-groups (p > 0.05). Strong correlation was also found between the expression of collagen type I and diameter of ulcer (Pearson correlation = 0.599, p = 0.05), however, no correlation found between weight loss with the expression of collagen type I (Pearson correlation = -0.102, p = 0.66), and the ulcer diameter (Pearson correlation = 0.022, p = 0.92). Conclusion: Gold sea cucumber had a potential benefit to be used as a traumatic ulcer healing medicament. Water extract of gold sea cucumber able to accelerate traumatic ulcer healing by enhancing the production of collagen type I and reduce the diameter of ulcer. There is a strong correlation between collagen type 1 expression and diameter of ulcer, and a weak correlation found between body weight loss and collagen type I expression, also with reducing ulcer diameter.Keywords: Gold sea cucumber, Stichopus hermanii, healing process, traumatic ulcer.


Author(s):  
Abayomi O. Ige ◽  
Olubori S. Adekanye ◽  
Elsie O. Adewoye

Abstract Objectives Exposure to light-at-night (LAN) has been reported to impair blood glucose regulation. The liver modulates blood glucose through mechanisms influenced by several factors that include peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1α) and glucose-6-phosphatase (G6Pase). This study investigated the effect of intermittent exposure to green and white LAN on some hepatic glucose regulatory factors in male Wistar rats. Methods Animals were divided into three equal groups. Group I (control) was exposed to normal housing conditions. Groups II and III were each daily exposed to either green or white LAN for 2 h (7–9 pm) for 14 days. Body weight and blood glucose was monitored on days 0, 7, and 14. Thereafter, retro-orbital sinus blood was obtained after light thiopental anaesthesia and serum insulin was determined. Liver samples were also obtained and evaluated for glycogen, PGC-1α, and G6Pase activity. Insulin resistance was estimated using the HOMA-IR equation. Results Body weight and blood glucose on days 7 and 14 increased in groups II and III compared to control. Hepatic PGC-1α and G6Pase increased in group II (2.33 ± 0.31; 2.07 ± 0.22) and III (2.31 ± 0.20; 0.98 ± 0.23) compared to control (1.73 ± 0.21; 0.47 ± 0.11). Hepatic glycogen was 71.8 and 82.4% reduced in groups II and III compared to control. Insulin in group II increased (63.6%) whiles group III values reduced (27.3%) compared to control. Insulin resistance increased in group II (0.29 ± 0.09) compared to control (0.12 ± 0.03) and group III (0.11 ± 0.03), respectively. Conclusions Exposure to 2 h green and white LAN in the early dark phase increases hepatic glycogenolysis and gluconeogenetic activities resulting in increased blood glucose. In male Wistar rats, exposure to green but not white LAN may predispose to insulin resistance.


2010 ◽  
Vol 35 (4) ◽  
pp. 526-533 ◽  
Author(s):  
Eric D.B. Goulet ◽  
Zareen Khursigara ◽  
Réjeanne Gougeon ◽  
José A. Morais

The frailty syndrome is associated with inflammation, hypercortisolemia, and cardiovascular diseases, all of which are linked with insulin resistance. But whether frailty is characterized by insulin resistance is unclear, especially in the postprandial state. The prevalence of underweight with frailty is high. We wondered whether hypermetabolism associated with inflammation and hypercortisolemia could increase the thermic effect of food (TEF) and contribute to the frailty-associated body weight loss. In this study, we determined whether insulin sensitivity and TEF responses differ between frail and healthy elderly persons following a meal. Ten healthy and 13 frail elderly women were recruited and studied during the 5 h following the ingestion of a standardized liquid mixed-meal test. Areas under the curve (AUC) for glucose and insulin, and the product of AUC glucose × AUC insulin × 10−6 (PGI) were used as indices of insulin sensitivity. TEF was measured by indirect calorimetry. Following the meal, glucose and insulin AUCs and PGI were significantly higher in frail than in healthy elderly women and, except for the insulin AUC; these differences remained significant after adjustment for age, body weight, and physical activity. Physical activity, determined by questionnaire, was the single best predictor of PGI, explaining 27% of its variance. There was no difference in TEF between groups, and it did not correlate with any significant variable measured. Our results suggest that postprandial insulin resistance is higher in frail than in healthy elderly women, and TEF is similar, indicating that both processes do not contribute to the propensity for body weight loss.


Author(s):  
Dayo Rotimi Omotoso ◽  
Adeniran Oluwadamilare Akinola ◽  
Ibifuro Brown

To assess the effect of methanolic leaf extract of Caladium bicolor on the histomorphology of gastrointestinal tissues of experimental animals. Twenty four Wistar rats (weighing between 175-190 g) were randomly and equally divided into four groups which include one control group (CG) and three treatment groups (TG I, TG II and TG III). The CG was administered with distilled water [2 ml/kg body weight (b.w.)] while TGs I, II and III were administered with 100 ml/kg, 200 ml/kg and 300 ml/kg (b.w.) of C. bicolor extract respectively. All administrations were done orally and once daily for a period of thirty days. The body weight of all animals was recorded at the beginning and end of study. After the period of study, gastric and small intestinal tissues of experimental animals were harvested, processed, converted to tissue blocks and sectioned. Tissue sections were stained using Haematoxylin and Eosin (H&E) technique. Thereafter, stained sections microscopically examined for observable histopathological changes within study tissues. The results of this study showed that exposure to C. bicolor extract causes significant (p < 0.05) body weight loss in TGs I-III compared to CG. In addition, prominent histopathological changes were observed in gastrointestinal tissues of experimental animals in TGs I-III including gastric mucosal surface erosion and intestinal villi degeneration compared to normal gastrointestinal histomorphology of CG animals. These histopathological changes may be associated with toxic effect of phytochemicals constituents of the extract. Therefore, its application for therapeutic purposes needs to be thoroughly re-validated or perhaps disallowed where alternative therapeutic agents with minimal toxic potential exist.


Endocrinology ◽  
2007 ◽  
Vol 148 (11) ◽  
pp. 5238-5247 ◽  
Author(s):  
Miriam García-San Frutos ◽  
Teresa Fernández-Agulló ◽  
Alain J. De Solís ◽  
Antonio Andrés ◽  
Carmen Arribas ◽  
...  

Insulin, like leptin, is considered as a lipostatic signal acting at a central level. Aging and age-associated adiposity have been related to the development of leptin resistance in Wistar rats. In the present article, hypothalamic insulin response during aging has been studied in Wistar rats. Thus, the effects of intracerebroventricular infusion of insulin during a week on food intake and body weight as well as insulin signal transduction after acute intracerebroventricular insulin administration have been studied in 3-, 8-, and 24-month-old rats. To explore the possible role of age-associated adiposity, these experiments were also performed in 8- and 24-month-old rats after 3 months of food restriction to reduce visceral adiposity index to values below those of young animals. Intracerebroventricular administration of insulin during a week was more efficient at reducing food intake and body weight in 3-month-old rats than in 8- and 24-month-old rats. Hypothalamic insulin-stimulated insulin receptor, GSK3, AKT, and p70S6K phosphorylation decreased with aging. Insulin receptor and IRS-2 phosphoserine was increased in 24-month-old rats. Food restriction improved both insulin responsiveness and insulin signaling. These data suggest that Wistar rats develop hypothalamic insulin resistance with aging. This can be explained by alterations of the signal transduction pathway. The fact that food restriction improves central insulin response and signal transduction points to the age-associated adiposity as a key player in the development of central insulin resistance.


2014 ◽  
Vol 58 (4) ◽  
pp. 377-381 ◽  
Author(s):  
Luciana da Conceição Antunes ◽  
Manoela Neves da Jornada ◽  
Jessica Lorenzzi Elkfury ◽  
Kelly Carraro Foletto ◽  
Marcello Casaccia Bertoluci

Objective: The objective of this study was to evaluate the association between insulin-resistance and fasting levels of ghrelin and PYY in Wistar rats. Materials and methods: A total of 25 male Wistar rats, weighing 200-300 g, was included in this study. The animals were maintained in cages with a 12/12h light-dark cycle and fed standard chow and water ad libitum. After 12-h overnight fasting, ghrelin, PYY, insulin and glucose values were determined. Insulin resistance was assessed by means of the HOMA-IR, which was ranked and the median was used as a cut-off value to categorize insulin-resistance. HOMA-IR values equal and above 2.62 were considered insulin-resistant (IR) while values below 2.62 were considered insulin sensitive (IS). Differences between means were determined using the Student t-test. Multiple regression and Pearson’s correlation test were used to evaluate the association between variables. Results: HOMA-IR median IQ range values for IS and IR groups were, respectively, 1.56 (0.89 – 2.16) vs. [4.06 (3.50 – 4.61); p < 0.001]. The IR group presented increased levels of fasting ghrelin, PYY and insulin respectively: [50.35 (25.99 – 74.71) pg/mL vs. 12.33 (8.77 – 15.89) pg/mL; p = 0.001]; [54.38 (37.50 – 71.26) pg/mL vs. 33.17 (22.34 – 43.99) pg/mL; p = 0.016]; [18.04 (14.48 – 21.60) uU/mL vs. 7.09 (4.83 – 9.35) uU/mL; p = 0.001]. Ghrelin, but not PYY, correlated linearly and positively with HOMA-IR: ghrelin vs. HOMA-IR (r = 0.52; p = 0.008), and PYY vs. HOMA-IR (r = 0.22; p = 0.200). This correlation was independent of body weight. Conclusion: Fasting ghrelin and PYY serum levels are increased in lean, relatively insulin resistant Wistar rats, and this increase is independent of weight.


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