Diabetic Pregnant Rats Research Articles

Investigation of diabetes-related molecular changes in embryo-endometrium crosstalk

The primary aim of this study was to explore the impact of diabetes on matrix metalloproteases and tissue inhibitors, crucial factors for successful implantation, and to elucidate the molecular mechanisms that undergo changes in the endometrium and the embryo during diabetic pregnancies. In this investigation, we established a streptozotocin-induced diabetic pregnant rat model. Microarray analysis followed by RT-PCR was utilized to identify gene regions exhibiting expression alterations. Subsequently, we assessed the effects of MMPs and tissue inhibitors using ELISA and immunohistochemistry techniques, in addition to analyzing changes at the genetic level. Diabetes led to the upregulation of MMP3, MMP9, and MMP20 on the 6.5th day of pregnancy, while causing the downregulation of MMP3, MMP9, and MMP11 on the 8.5th day of pregnancy. TIMP1 expression was downregulated on the 8.5th day compared to the control group. No statistically significant differences were observed between the groups regarding other TIMP expressions. KEGG pathway analysis revealed that diabetes induced alterations in the expression of genes associated with certain microRNAs, as well as signaling pathways such as cAMP, calcium, BMP, p53, MAPK, PI3K-Akt, Jak-STAT, Hippo, Wnt, and TNF. Additionally, gene ontology analysis unveiled changes in membrane structures, extracellular matrix, signaling pathways, ion binding, protein binding, cell adhesion molecule binding, and receptor-ligand activity. This study serves as a valuable guide for investigating the mechanisms responsible for complications in diabetic pregnancies. By revealing the early-stage effects of diabetes, it offers insight into the development of new diagnostic and treatment approaches, ultimately contributing to improved patient care.

Eupatilin mitigates Gestational diabetes in streptozotocin-induced diabetic pregnant rats through the Regulation of inflammation and oxidative stress

Gestational diabetes mellitus (GDM) is a common metabolic disease that is typically diagnosed in pregnant women. The current study was aimed at disclosing the salutary activities of eupatilin against streptozotocin (STZ)-induced GDM in rats. The pregnant rats were induced with GDM and then treated with eupatilin for 20 days. The bodyweight, pup numbers and survival, glucose, and insulin levels were estimated. The levels of biochemical markers, antioxidants, and lipid profiles were measured using kits. The histopathological analysis was done on the pancreas and liver tissues. The eupatilin effectively reduced glucose and boosted insulin levels in the GDM rats. The pup numbers and their survival index were increased by the eupatilin treatment. The lipase, creatinine, AST, ALT, and urea levels were effectively reduced by the eupatilin in the GDM rats. Eupatilin treatment also decreased oxidative stress by increasing antioxidant levels and reducing inflammatory cytokine levels in the GDM rats. The cholesterol, LDL, and triglyceride levels were effectively decreased, and HDL was elevated by eupatilin. The results of histopathological analysis of both liver and pancreatic tissues also demonstrated the therapeutic properties of eupatilin. In conclusion, the current results prove that eupatilin can be an effective salutary candidate to treat GDM.

Nerolidol Attenuates Diabetic Embryopathy in Streptozotocin-induced Diabetic Pregnant Rats by Reducing Embryonic and Maternal Oxidative Stress

Background Pregnancy complicated by diabetes leads to congenital disorders, spontaneous abortion, and neonatal morbidity and mortality, which are termed diabetic embryopathy or fetopathy. Objectives In this work, we planned to investigate the therapeutic potentials of nerolidol against streptozotocin (STZ)-induced diabetic embryopathy in rats through attenuating maternal and fetal oxidative stress. Materials and Methods The male and female Wistar rats were allowed to mate for a night at a 1:1 ratio. After the confirmation of pregnancy, the rats were administered 40 mg/kg of STZ (i.p.) to initiate diabetes and treated with 20 and 40 mg/kg of nerolidol. The changes in food intake, body weight, blood glucose, and urine output were regularly monitored. The levels of lipid profiles were estimated using assay kits. The oxidative stress and antioxidant biomarkers in the liver tissues and embryonic fractions were measured using assay kits. Results The nerolidol treatment considerably depleted the blood glucose and urine output and augmented the body weight and diet intake in diabetic rats. The nerolidol suppressed the cholesterol (Ch), triglycerides (TG), and very low density lipoprotein (VLDL) and elevated the high density lipoprotein (HDL) level in diabetic pregnant rats. The maternal and embryonic oxidative stress levels are effectively reduced by the nerolidol treatment by decreasing the malondialdehyde (MDA) and reactive oxygen species (ROS) levels. The levels of antioxidants were also increased by the nerolidol on both liver and embryonic fractions of diabetic pregnant rats. Conclusion Our results exhibited that the nerolidol treatment considerably reduced embryonic and maternal oxidative stress and embryonic deaths. Hence, it can be a hopeful therapeutic candidate to treat diabetic embryopathy.

Tert-butylhydroquinone Mitigates Renal Dysfunction in Pregnant Diabetic Rats via Attenuation of Oxidative Stress and Modulation of the iNOs/ NFkB/TNF Alpha Signalling Pathway.

The aim of the study was to determine the effect of tert-butylhydroquinone (tBHQ) supplementation on some biochemical parameters in pregnant diabetic rats and the foetus. The global incidence of gestational diabetes mellitus (GDM) has been on the increase despite current interventional therapies, underscoring the need for alternative or complementary therapeutic approaches. The objective is to determine the effect of tBHQ on blood glucose, insulin resistance, body weight, relative liver and kidney weights, serum lipid profile (total cholesterol, triacylglycerol, high-density lipoprotein cholesterol and very low-density lipoprotein cholesterol), liver function (albumin, aspartate and alanine amino transaminases) and kidney function markers (urea, creatinine and uric acid) in the sera, and study maternal and foetal renal levels of oxidative stress and inflammatory markers, foetal weights and histology of the kidney of streptozotocin (STZ)-induced GDM in rats. Twenty female pregnant rats were used, and they were divided into four groups of control (normal pregnancy), disease (diabetic untreated), metformin (received 200 mg/kg metformin dissolved in distilled water) and tBHQ groups (received 25 mg/kg tBHQ in 1% corn oil), respectively, with five rats in each group. GDM was induced in the disease and treated groups by intraperitoneal injection of STZ (45 mg/kg in sodium citrate buffer, pH 4.5). STZ induction in the disease group significantly increased their blood glucose levels (P<0.05), altered their body and foetal weights, relative liver and kidney weights, serum lipid profile, liver and kidney function markers in the sera (relative to the control), inducing oxidative stress and inflammation to the maternal and foetal kidneys and altering the maternal kidney histology, which was found to be improved following supplementation with tBHQ in a manner akin to or even better than metformin. tBHQ was found beneficial in protecting the foetal kidneys against oxidative stress and the foetus against mortality arising from maternal hyperglycaemia. Finally, the study showed the potential of tBHQ in mitigating histological changes in the maternal kidney arising from STZinduced hyperglycemia in rats.

Increased Nuclear FOXP2 Is Related to Reduced Neural Stem Cell Number and Increased Neurogenesis in the Dorsal Telencephalon of Embryos of Diabetic Rats through Histamine H1 Receptors.

Diabetic rat embryos have increased cortical neurogenesis and neuron maturation, and their offspring presented altered neuron polarity, lamination, and diminished neuron excitability. The FOXP2 overexpression results in higher cortical neurogenesis by increasing the transition of radial glia to the intermediate progenitor. Similarly, histamine through H1-receptor activation increases cortical neuron differentiation. Indeed, blocking the H1-receptor by the systemic administration of chlorpheniramine to diabetic pregnant rats prevents increased neurogenesis. Here, we explore the relationship between the H1-receptor and FOXP2 on embryo neurogenesis from diabetic dams. Through qRT-PCR, Western blot, immunohistofluorescence, and flow cytometry, we showed an increased FOXP2 expression and nuclear localization, a reduced Nestin expression and -positive cells number, and a higher PKCα expression in the cortical neuroepithelium of fourteen-day-old embryos from diabetic rats. Interestingly, this scenario was prevented by the chlorpheniramine systemic administration to diabetic pregnant rats at embryo day twelve. These data, together with the bioinformatic analysis, suggest that higher H1-receptor activity in embryos under high glucose increases FOXP2 nuclear translocation, presumably through PKCα phosphorylation, impairing the transition of radial glia to intermediate progenitor and increasing neuron differentiation in embryos of diabetic rats.

Visnagin Attenuates Gestational Diabetes Mellitus in Streptozotocin-induced Diabetic Pregnant Rats via Regulating Dyslipidemia, Oxidative Stress, and Inflammatory Response

Background: Gestational diabetes mellitus (GDM) is a condition of glucose intolerance and insulin resistance only diagnosed during pregnancy. GDM has exhibited several adverse effects on both mother and offspring. The current research focuses on discovering visnagin’s beneficial properties against the streptozotocin (STZ)-induced GDM in rats via alleviating the inflammation and oxidative stress. Materials and Methods: GDM was caused in the pregnant rats by the administration of 25 mg/kg of STZ by the intraperitoneal route and then treated with 20 mg/kg of visnagin for 20 consecutive days. The rats’ body weight was measured, and fasting blood glucose (FBG) status was determined using a standard glucometer. The contents of total cholesterol (TCh), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were assessed using kits. The MDA level, total antioxidant capacity (TAC) status, and activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST) were determined using assay kits. Kits also assessed the contents of TNF-α and IL-1β. The contents of TNF-α and IL-1β effectively improved the body weight and decreased the FBG status in the GDM rats. The visnagin also decreased the TCh, TG, and LDL, and elevated the HDL content. The content of MDA was decreased and the visnagin treatment increased SOD, CAT, GST, and GPx, and the visnagin treatment increased SOD, CAT, GST, and GPx activities SOD, CAT, GST, and GPx activities. The visnagin effectively decreased the STZ-induced histopathological alterations in the pancreas. Conclusion: Altogether, our investigation results suggest a beneficial role visnagin against STZ-induced GDM in rats via inhibiting the inflammatory responses. Hence, it can be a talented therapeutic candidate for the successful management of GDM.

Ginger Could Improve Gestational Diabetes by Targeting Genes Involved in Nutrient Metabolism, Oxidative Stress, Inflammation, and the WNT/β-Catenin/GSK3β Signaling Pathway

This study aimed to evaluate the effect in female rats of 6 weeks of ginger consumption on gestational diabetes by assessing glucose and lipid metabolism, oxidative damage, inflammation, and the WNT/β-catenin/glycogen synthase kinase-3 beta (GSK3β) signaling pathway. In this study, 40 adult female rats were divided into 4 equal groups as follows: pregnant rats, pregnant rats with diabetes, pregnant rats consuming ginger, and pregnant rats with diabetes consuming ginger. Induction of diabetes on day 0 of pregnancy was induced by streptozotocin (STZ) injection. Insulin, glucose, and lipid profiles as metabolic factors were measured along with the hepatic expression of glucose transporter type 4 (GLUT4), mechanistic target of rapamycin complex 1 (mTORc1), sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor α (PPAR-α), β-catenin, GSK3β, PPAR-g, nuclear factor-κB (NF-kB), and nuclear factor erythroid 2-related factor 2 (Nrf2). The levels of tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and oxidative parameters were measured in the liver. The level of metabolic factors was significantly impaired in diabetic pregnant rats compared to the control group. However, ginger improved these parameters in the diabetic pregnant—ginger group compared to the diabetic pregnant group. The hepatic expression of genes involved in metabolism, oxidative stress, inflammation, and the wingless and int-1 (WNT) signaling pathway was significantly impaired in diabetic pregnant rats, while ginger improved them in the hepatic tissue of diabetic pregnant rats. It can be concluded that ginger could improve gestational diabetes by genes involved in metabolism, the WNT signaling pathway, oxidative stress, and inflammation. These results suggest that ginger can be an adjunct drug during pregnancy as a metabolic modulator.

Nigericin Abrogates Maternal and Embryonic Oxidative Stress in the Streptozotocin-Induced Diabetic Pregnant Rats.

Hyperglycemic exposure in diabetic pregnancy can lead to many developmental changes, such as delayed development, fetal malformations, and fetal/embryo death. These detrimental complications are collectively known as diabetic embryopathy or teratogenesis. The current study focuses to discover the therapeutic properties of the nigericin against the STZ-stimulated diabetic embryopathy via alleviation of maternal and embryonic oxidative stress. The male and female rats at a 1:1 ratio were permitted to mate overnight to establish the course of pregnancy. The pregnant rats were distributed into four groups control, diabetic pregnant (via administering 40mg/kg of STZ), and diabetic + 10 and 20mg/kg of nigericin-administered (via oral gavage from days 5 to 12) groups, respectively. The glucose level, urine output, diet intake, and body weight were determined carefully. The embryo and placenta weight and implantation rates were examined, and data were tabulated. The total protein and lipid profiles were assessed using respective kits. The oxidative stress markers and antioxidant enzymes were examined using respective assay kits. The 10 and 20mg/kg of nigericin treatment decreased the glucose level and urine output and improved the diet intake and body weight gain in diabetic pregnant rats. The nigericin also decreased the total protein, cholesterol, triglycerides, and very-low-density lipoprotein (VLDL) and improved the high-density lipoprotein (HDL) in the serum of pregnant rats. The levels of malondialdehyde (MDA), reactive oxygen species (ROS), and protein carbonyls were decreased by the nigericin in both liver and embryos of the pregnant rats. The levels of glutathione (GSH), total thiols, and activities of catalase (CAT), glutathione reductase (GR), superoxide dismutase (SOD), glutathione peroxidase (GPX), and glutathione S-transferase (GST) were improved by the nigericin in the diabetic pregnant rats. Altogether, these results provide evidence that nigericin treatment remarkably attenuates the diabetes-stimulated embryopathy in rats. The nigericin effectively decreased embryo lethality, reduced glucose and dyslipidemia, and relieves oxidative stress via upregulating the antioxidant enzyme activities. Hence, it can be a talented therapeutic agent to treat diabetic pregnancy-associated complications.

Benefits of Vitamin D Supplementation on Pregnancy of Rats with Pregestational Diabetes and Their Offspring.

Studies on vitamin D supplementation have been performed in experimental and clinical investigations considering gestational diabetes and/or vitamin D deficiency in pregnancy. However, the results are controversial and few present the effects and mechanisms of this micronutrient on pregestational diabetes. The objective of this study was to evaluate the effect of vitamin D on the pregnancy of rats with pre-existing diabetes and their fetuses. Pregestational diabetes was induced in Sprague-Dawley rats at birth. The adult diabetic and nondiabetic rats were orally administered with vitamin D (cholecalciferol) throughout the pregnancy. The diabetes status was monitored during pregnancy by an oral glucose tolerance test (OGTT). At the end of the pregnancy, pancreas and blood samples were collected for morphological analyses and lipid peroxidation measurements, respectively. The influence of vitamin D treatment on reproductive outcomes, fetal growth, and development were compared to those of untreated diabetic and nondiabetic pregnant rats. P < 0.05 was considered a significant statistical limit. The diabetic rats given vitamin D had a greater number of insulin-positive cells, contributing to reduced blood glucose levels and thiobarbituric acid reactive substance concentrations (TBARS-an indicator of membrane lipid peroxidation), and increased reduced thiol group levels, contributing to suitable intrauterine conditions for better fetal development, which was confirmed by higher fetal viability rates. Thus, this study shows the effects and mechanisms of vitamin D supplementation on pre-existing diabetes in pregnant rats, confirming its beneficial effects on maternal redox status and glycemic control, and the decline of adverse maternal-fetal repercussions.

Ganoderma lucidum Modulates Glucose, Lipid Peroxidation and Hepatic Metabolism in Streptozotocin-Induced Diabetic Pregnant Rats.

The consumption of functional foods, such as mushrooms, apparently influences Gestational Diabetes Mellitus (GDM), and brings benefits to maternal-fetal health. Ganoderma lucidum contains a variety of bioactive compounds, such as polysaccharides, proteins and polyphenols that are able to control blood glucose and be used in anti-cancer therapy. We aimed to evaluate the effects of the consumption of Ganoderma lucidum (Gl) on maternal-fetal outcomes in streptozotocin-induced GDM (GDM-STZ). Pregnant rats were exposed to Gl (100 mg/kg/day) before and after the induction of GDM-STZ (single dose 40 mg/kg) on the eighth pregnancy day. Biochemical and oxidative stress parameters, reproductive performance and morphometry of fetuses were assessed. Gl reduced the glycemic response in the oral glucose tolerance test. Moreover, Gl decreased AST and ALT activities. GDM increased lipid peroxidation, which was reverted by Gl. Catalase and glutathione peroxidase activities were decreased in GDM and the administered Gl after the fetus implantation increased catalase activity. Measurements of the fetal head, thorax, craniocaudal and tail showed greater values in fetuses from rats exposed to Gl compared to GDM. Ganoderma lucidum has an encouraging nutritional and medicinal potential against GDM, since it modifies glucose metabolism, reduces lipid peroxidation, and has protective effects in fetuses born from GDM dams.

Effect of swimming exercise, insulin-associated or not, on inflammatory cytokines, apoptosis, and collagen in diabetic rat placentas.

Physical exercise is an important therapeutic agent for women with diabetes during gestation. However, its histophysiological consequences for the placenta remain unclear. In this study, we evaluated the expression of VEGF-A, IL1ß, TNFα, and type I collagen in the placentas of diabetic rats subjected to a swimming program. Thirty rats were divided into the following groups: CG, pregnant nondiabetic rats; CEG, nondiabetic pregnant rats subjected to swimming; DG, pregnant diabetic rats; DEG, pregnant diabetic rats subjected to swimming; DIG, pregnant diabetic rats treated with insulin; DIEG, pregnant diabetic rats treated with insulin and subjected to swimming. Diabetes was induced using streptozotocin [50mg/kg intraperitoneally (i.p.)], and insulin was administered at a dose of 5U/day i.p. (2U at 10am and 3U at 7pm) in the DIG group; in the DIEG group, insulin was administered at a dose of only 2U/day at 7pm. The rats were sacrificed on the 20th day of gestation. There was an increase in the expression of IL-1β, TNF-α, VEGF-A, and type I collagen and a higher apoptotic index in the placentas of the DG and DEG groups, but there was a reduction in glycemia in the latter group. In the DIG and DIEG groups, the levels remained similar to those of the control; however, in these groups the reduction was more significant for all analyzed parameters. Therefore, in rats induced to diabetes during pregnancy, swimming, although reducing glycemic levels, did not prevent immunohistochemical changes in the placenta, suggesting the need for a multidisciplinary protocol associated with traditional pharmacological treatment.

Myrtenol alleviates oxidative stress and inflammation in diabetic pregnant rats via TLR4/MyD88/NF-κB signaling pathway.

Gestational diabetes mellitus (GDM) is a special kind of diabetes that arises only during pregnancy. A woman with GDM has a higher risk of developing type-2 diabetes and other metabolic diseases. In this exploration, we intended to scrutinize the therapeutic actions of Myrtenol against the streptozotocin (STZ)-provoked GDM in rats. GDM was provoked in the pregnant rats via injecting the 1% of STZ (25 mg/kg) and then treated with the 50 mg/kg of myrtenol. The glucose level and bodyweight of animals were noted. The lipid profile, that is, total cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein (HDL) was determined by respective kits. The lipid peroxidation and antioxidants status were examined using assay kits. The status of proinflammatory markers was investigated by assay kits. The messenger RNA (mRNA) expressions of TLR4/MyD88/NF-κB signaling proteins were studied by reverse transcription polymerase chain reaction analysis. The hepatic and pancreatic tissues were examined microscopically. Myrtenol treatment notably decreased the status of blood glucose and lipid profile and improved the HDL in the GDM rats. The status of lipid peroxidation and inflammatory markers were substantially reduced by the myrtenol and it enhanced the antioxidants status of GDM animals. Myrtenol treatment remarkably downregulated the mRNA expressions of TLR4/MyD88/NF-κB signaling proteins. The histological findings also proved the therapeutic actions of myrtenol. Altogether, the findings of this investigation unveiled the therapeutic actions of the myrtenol against the STZ-provoked GDM in rats. Myrtenol could be a promising therapeutic agent to treat GDM in the future.

Adiponectin agonist treatment in diabetic pregnant rats.

Gestational diabetes mellitus (GDM) reduces maternal adiponectin and docosahexaenoic acid (DHA) materno-fetal transfer, which may have negative consequences for the offspring. Our aim was to evaluate the effects of the administration of a novel adiponectin agonist (AdipoRon) to GDM rats on the long-term consequences in glycaemia and fatty acids (FA) profile in the offspring. Pregnant rats were randomized to three groups: GDM rats (GDM, n = 8), GDM rats treated with AdipoRon (GDM + ADI, n = 9), and control rats (n = 10). Diabetes was induced with streptozotocin (50 mg/kg) on day 12 of gestation. GDM+ADI received 50 mg/kg/day AdipoRon from day 14 until delivery. Glycaemia and FA profile were determined in mothers and adult offspring (12 weeks old). AdipoRon tended to reduce fasting glucose in diabetic mothers. Diabetic rats presented the foetus with intrauterine growth restriction and higher adiposity, which tried to be counteracted by AdipoRon. In the adult offspring, both GDM + ADI and control animals showed better glucose recovery after oral glucose overload with respect to GDM. DHA in offspring plasma was significantly reduced in both GDM and GDM + ADI compared to controls (P = 0.043). Nevertheless, n-6/n-3 polyunsaturated FA (PUFA) ratio improved in plasma of GDM + ADI adult offspring (GDM: 14.83 ± 0.85a%; GDM + ADI: 11.49 ± 0.58b%; control: 10.03 ± 1.22b%, P = 0.034). Inflammatory markers and oxidative stress were reduced in the adult offspring of AdipoRon-treated mothers. In conclusion, AdipoRon administration to pregnant diabetic rats improved glycaemia in the mothers and long-term glucose tolerance in the offspring. In addition, it tended to reduce excessive foetal fat accumulation and improved n-6/n-3 PUFA ratio significantly in offspring at the adult state.

Quercetin improved histological structure and upregulated adiponectin and adiponectin receptors in the placenta of rats with gestational diabetes mellitus

IntroductionGestational diabetes mellitus (GDM) is a metabolic syndrome among pregnant mothers that increases the risk of developing growth disorders in the fetus and the placenta. Adiponectin is an adipokine, which plays a central role in the regulation of glucose and lipid metabolism, energy homeostasis, and insulin resistance in various tissues. Quercetin is a natural flavonoid with beneficial effects in the diabetic animal model, but data related to its effect on histological change and adiponectin system in the placenta of GDM are limited. In the current study, some histological changes and expression of adiponectin and its two receptors in the placenta of rats with GDM were investigated. MethodsThis study was carried out on placentas from the rodent model. To induce GDM, female rats were treated with a single dose of STZ. Placenta tissue was harvested and stained by PAS method. Protein and mRNA levels of adiponectin and its two receptors were assessed by immunohistochemistry and Real time PCR analysis, respectively. ResultsThe results showed the increased number of glycogen cells and thickness of the labyrinth interhemal membrane (LIM) in the embryonic part of the placenta in diabetic rats, while the use of quercetin significantly prevented their increase in diabetic rats. Treatment of the diabetic group with quercetin caused significantly increased adiponectin expression and decreased its receptors.The immunohistochemical study revealed the expression of AdipoR2 in the cytoplasm of syncytiotrophoblast and cytotrophoblast cells. DiscussionThe results indicated that quercetin in pregnant diabetic rats could attenuate the histological abnormalities and improved adiponectin system dysregulation in the placenta.

Moringa oleifera decrease blood sugar level and blood pressure in pregnant diabetic rats

Abstract It has been known that 10% of pregnancy will undergone diabetes and increases the risk of hypertension, premature birth, intrauterine growth disorders, perinatal death, kidney and liver failure, pre-postpartum hemorrhage, and maternal death. Many treatment regimen had been use however still there were no satisfied result. Recently, Moringa oleifera was popular as miracle tree that had many health properties. Many paper had report its anti-cancer properties, antipyretic, antiepileptic, anti-inflammatory, antiulcer, antispasmodic, diuretic, antihypertensive, antioxidant, antidiabetic, hepatoprotective, antibacterial, antifungal, antiatherosclerotic, heart and blood circulation stimulant. Hence we conduct this research to dig the role of moringa oleifera in diabetic pregnant rat. We used 30 pregnant rats divided into 6 groups of treatment, i.e two control group and others were treatment group of different doses of Moringa powder at 100, 200, 400 and 800 mg/day/kg. Alloxan 150 mg/day/kg was used to induce diabetic animal model. Blood glucose was measure using glucostick methods and blood pressure was measure using the tail-cuff method using CODA blood pressure analyzer. In this study, it can be concluded that the administration of Moringa leaf powder (Moringa oleifera) at a dose of 200 mg/day/kg BW decreased glucose levels and decreased blood pressure at a dose of 400 mg/day/kg BW on in diabetic pregnant animal model.

Beneficial effects of walnut (Juglans regia L.)\xa0oil-derived polyunsaturated fatty acid prevents a prooxidant status and hyperlipidemia in pregnant rats with diabetes

BackgroundGestational diabetes mellitus has a long-term effect on pregnant women. Walnut (Juglans regia L.) oil-derived polyunsaturated fatty acid (PUFA) possesses multifarious pharmacological activities. This study investigated the beneficial effects of walnut oil-derived PUFA on glucose metabolism, pregnancy outcomes, oxidative stress, and lipid metabolism in gestational diabetes mellitus.MethodsThe GDM rat model was generated by intraperitoneal injection of streptozotocin (40 mg/kg) on gestational day (GD) 6, GD7 and GD8. The differences between groups were estimated using one-way ANOVA followed by the Tukey’s multiple comparison test for post-hoc analysis.ResultsThe results indicated that PUFA could mitigate GDM in pregnant diabetic rats, as embodied by the decrease of fasting blood glucose and the increase of plasma insulin and hepatic glycogen levels. Also, PUFA could suppress oxidative stress in pregnant diabetic rats, as reflected by the decrease of malondialdehyde content, an increase of superoxide dismutase, catalase and gutathione peroxidase activities. PUFA could also mitigate the abnormal changes of lipid profiles in plasma and hepatic tissue. Moreover, the relative mRNA expression of sterol regulatory element-binding transcription factor-1, stearoyl-CoA desaturase-1, fatty acid synthase, and acetyl-coenzyme A carboxylase, was suppressed by PUFA in pregnant diabetic rats.ConclusionsThese results suggested that PUFA supplementation during pregnancy is beneficial in preventing diabetic complications in pregnant rats.

Severity of prepregnancy diabetes on the fetal malformations and viability associated with early embryos in rats†.

Preexisting/pregestational diabetes enhances the risk of birth defects. Several factors have been involved during the implantation process, such as cytokines (granulocyte-macrophage-colony-stimulating factor [GM-CSF]). The objective was to evaluate the effects of two levels of diabetes on the redox status of preimplantation embryos during the implantation process to comprehend how both are involved in embryo and fetal viability against maternal diabetes. Female Sprague-Dawley rats received streptozotocin at birth (mild diabetes [MD]) or at adulthood (severe diabetes [SD]) to obtain two experimental diabetes intensities. After confirming the diabetic status, the nondiabetic and diabetic groups were mated around day 110 of life. At gestational day (GD) 21, fetuses were assessed for viability and malformations and ovaries for embryo loss before implantation. Other pregnant nondiabetic and diabetic rats were sacrificed at GD2-4 for maternal and preimplantation embryo oxidative stress markers, maternal serum insulin, uterine fluid GM-CSF, and preimplantation embryo morphological analysis. MD and SD caused abnormal redox levels, lower GM-CSF and insulin levels during the preimplantation period, and embryonic loss before implantation. SD caused lower fetal viability and higher fetal malformation percentages at GD21. The SD dam-derived preimplantation embryos presented lower glutathione levels and higher thiobarbituric acid reactive substances concentration at GD3 and an increased frequency of abnormal preimplantation embryos at GD4. In conclusion, preexisting diabetes leads to complications in the implantation process. Furthermore, maternal oxidative stress and other metabolic changes alter the redox state and morphological structure of preimplantation embryos, contributing to damaged growth and development in late pregnancy.

Protective effects of syringin against oxidative stress and inflammation in diabetic pregnant rats via TLR4/MyD88/NF-κB signaling pathway

Gestational diabetes (GDM) is common in pregnancies due to the inflammation and oxidative stress-mediated insulin resistance. In the present study, GDM was induced in the Wistar rats by administering the streptozotocin to elucidate whether the administration of syringin (50 mg/kg/day) during pregnancy could improve maternal glycemia and protect against the complications of GDM. The animals were assessed for their morphological changes in the β-islets of Langerhans and their insulin-producing ability, inflammatory cytokine markers, and the involvement of TLR4/MyD88/NF-κB signaling pathway using RT-PCR. The results demonstrated that the onset of GDM demonstrated pancreatic tissue degeneration in the islets of Langerhans with a significant increase in oxidative stress and reduced antioxidant enzymes. Besides, the mRNA expression levels of TLR4, MyD88, NF-Kβ p65; NLRP3 mRNA were profoundly increased in GDM rats compared to normal pregnant rats. On the other hand, syringin administered GDM rats abrogated the oxidative stress and attenuated the level of the inflammatory cytokines. Intriguingly, the decrease in TLR4 expression and the downstream molecules of MyD88, NF-κB, and NLRP3 were also observed in syringin administered GDM rats that indicate the insulin secretion stimulatory actions of syringin through the suppression of TLR4 signaling. These novel findings of the study provide evidence that syringin could be a probable candidate to be used in the treatment of gestational diabetes in the future.

Effect of Diabetes Mellitus on Uterine contractility in Pregnant Rat Model: Possible Role of L ̵ carnitine

Objective: to detect the changes induced by STZ induced diabetes on uterine contractility and expression of connexin 43 in pregnant rat and the possible role of L carnitine to detect the role of L Carnitine in a model of diabetic pregnant rat. Method:40 female Sprague Dawley rats were subdivided into four groups; G I (NC): normal pregnant rats, G II (DI): in which rats received single i.p injection of 40 mg/kg b.wt STZ at day 1 of pregnancy, G III (DI+CAR): in which rats received STZ as above, and then at day 3 of pregnancy, diabetic pregnant rats received daily i.p L carnitine injection at a dose of 100 mg/kg b.wt till end of pregnancy, and G IV (DI+INS): in which rats received STZ as above, and then at day 3 of pregnancy, diabetic pregnant rats received daily i.p insulin injection at a dose of 1 IU/100 g b.wt (till end of pregnancy. Plasma glucose and insulin level, uterine contractility, pathological changes were assessed at the end of the experiment and scarifying of rats. Results: STZ induced DM caused significant increase in plasma glucose level, decreased plasma insulin level, impaired uterine contractility, pathological changes in diabetic group compared to normal control group. L Carnitine caused significant improvement in the studied parameters.

Betaine alleviated hepatic and renal injury in diabetic pregnant rats: biochemical and histopathological evidences.

Pregnancy is the most intense physiological alteration in energy metabolism that women experience in their lifetime. Liver and kidney are the two most susceptible organs to energy metabolism. Diabetes is well-defined as a syndrome interfering with energy metabolism triggered by impaired blood glucose adjustment. Herein, protective effects of betaine on liver and kidney were evaluated in animal model of diabetic pregnancy. 32 dams were assigned into 4 equal groups: Control (C), Betaine (B, 1.5% w/w of total diet daily), Diabetic pregnancy (D), and Diabetic pregnancy treated with betaine (D + B). After physiological delivery, HbA1c concentration in whole blood, serum hepatic and renal biomarkers such as AST, ALT, ALP, urea and creatinine were measured. Also, liver and kidney tissue samples were examined under a light microscope. Diabetic pregnancy was found to be accompanied by increased HbA1c level, concentration of hepatic and renal biomarkers in blood samples, and a gamut of alterations such as apoptotic cells, biliary hyperplasia, sinusoidal dilation, basement membrane thickening, and Bowman's capsule dilation as observed in histopathological sections of the D group. Betaine supplementation significantly decreased AST, ALT, urea and creatinine in the D + B group compared to D group. Also, most of pathologic microscopic alterations were attenuated under betaine treatment in D + B group compared to D group. Findings of the current paper, for the first time, provided evidence regarding protective effects of betaine on liver and kidney function against maternal diabetes in an animal model of STZ-induced diabetic pregnancy.