Diabetic Female Rats Research Articles

Absence of sex differences in diabetes-induced suppression of KNDy neurons in rats.

Diabetes mellitus disturbs kisspeptin-neurokinin B-dynorphin A (KNDy) neurons in the arcuate nucleus (ARC), which regulate pulsatile luteinizing hormone (LH) secretion in both sexes. However, it remains unclear whether a sex-specific association with the negative effects of diabetes on KNDy neurons exists. Therefore, we examined mRNA expression in KNDy neurons of diabetic male and female rats 7 weeks after streptozotocin (STZ) injection using histochemistry. In gonad-intact rats, the numbers of Kiss1 and Pdyn mRNA-expressing cells in the ARC decreased in an STZ-dose-dependent manner; moreover, no sex-dependent association with STZ treatment was observed. In males, plasma LH and sex steroid levels decreased in diabetic rats. Conversely, those of females did not vary significantly between the control and diabetic rats. Kiss1 expression in the anteroventral periventricular nucleus was slightly affected in diabetic animals, but did not exhibit sex-dependent differences. In gonadectomized rats, the numbers of KNDy mRNA-expressing cells in the ARC and plasma LH levels decreased in diabetic male and female rats; however, sex-dependent differences did not exist. These results demonstrated that a sex-specific association with the negative effects of diabetes on KNDy neurons did not exist. Therefore, the stage of diabetes that induces the suppression of the hypothalamus may not vary according to sex.

Harnessing the therapeutic potential of bone marrow-derived stem cells for sciatic nerve regeneration in diabetic neuropathy

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes that affects the angiogenesis and myelination of peripheral nerves. In this study, we investigated the potential of mesenchymal stem cells (MSCs) transplantation to improve DPN by enhancing angiogenesis and remyelination in the sciatic nerve of streptozotocin (STZ)-induced diabetic female rats. The purpose of this study was to evaluate the therapeutic potential of mesenchymal stem cells as a possiblity for clinical intervention to alleviate the symptoms of diabetic peripheral neuropathy. We examined whether transplanted mesenchymal stem cells can produce new and restored angiogenesis, as well as promoting myelination. Overall, our findings suggest that MSCs transplantation has neuroprotective effects. This is particularly the case for Schwann cells. Transplantation may stimulate angiogenesis as well as remyelination of the sciatic nerve in experimentally-induced diabetic peripheral neuropathy. Behavioral assays, histological analysis, and molecular techniques were used to assess the effects of MSCs transplantation. Our results demonstrate that in diabetic rats signs of neuropathy were reversed following a single administration of bone marrow-derived MSCs. Morphological and morphometric analysis of the sciatic nerve revealed that diabetic rats displayed structural alterations that were attenuated with MSCs transplantation.Immunostaining analysis showed increased expression of S100 and VEGF in the sciatic nerve following MSCs transplantation. Western blotting analysis also revealed elevated levels of VEGF and CD31 in rats treated with MSCs compared to diabetic rats.

Assessed the Liver Injury Biomarker Following Candida Infection in Female Diabetic Rats

Assessed the Liver Injury Biomarker Following Candida Infection in Female Diabetic Rats

Comparative Evaluation of Diabetes Complication Using Liver Function Parameters as Indices between Male and Female Alloxan Induced Diabetic Rats

It is known that diabetes causes liver damage. On the other hand, because most cases of liver damage have been investigated in males, examining the relationship of this disease in both sexes is of great importance. This study was aimed at, comparatively evaluating diabetic complications using histopathological examination and liver function parameters as indices in alloxan-induced diabetic rats. A total of 24 male and female rats divided into four groups of six animals each were used for the experiment. Group A were female control, Group B were male control while group C and D were alloxan induced diabetic female and male rats respectively. Groups A and B were non diabetic rats fed with rat diet all through the experiment. Group C and D were diabetes induced with a single intraperitoneal injection of alloxan (120mg/kg). At the end of the inducement period, the rats were fasted overnight and sacrificed. Blood was collected by ocular puncture for the determination of fasting plasma glucose (FPG) and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TB), direct bilirubin (DB), total protein (TP) and albumin (ALB) using spectrophotometric method. Histology of the liver was determined by H and E technique. The results showed the experimental group C (365.83±43.6mg/dl) and D (368.94±43.93mg/dl) had significantly elevated levels of FPG when compared with the controls group A (116.00±9.11mg/dl) and B (108.33±5.5mg/dl) confirming the induction of diabetes (P=0.000). The liver of both male and female diabetic rats showed ballooning degeneration. In the males, these were arranged in normal sheets and cord around central vein in some areas of the center, on the other hand, the central vein of the female diabetic rats appears slightly enlarged containing blood clots and the arrangement of the hepatocytes in sheets or cords around the central vein was completely distorted. There was no significant difference (p>0.05) in the mean serum levels of ALP, AST, ALT, DB, TP and ALB in female diabetics when compared to male diabetic rats. The mean serum level of TB was significantly reduced (p=0.004) in female diabetics (0.53±0.05) than in the male diabetic albino rats (0.69±0.09). This study showed the liver histology and function are variably altered in diabetes mellitus. Further research on the causes of liver damage will help us to unravel the pathogenesis of diabetes and its complications.

Alcohol promotes liver fibrosis in high fat diet induced diabetic rats.

Type 2 diabetes (T2DM) and alcoholism are considered to be lifestyle-associated independent risk factors in fatty liver diseases (FLD) mediated cirrhosis and hepatocellular carcinoma (HCC). A combined effect of both these conditions may exacerbate the pathological changes and a pre-clinical exploration of this is expected to provide a mechanical detail of the pathophysiology. The present study aims to understand the effect of alcohol on pre- diabetic and type 2 diabetic female Wistar rats. In this experimental study, 12 Wistar rats (180-220 g) were randomly assigned into three groups: Normal (fed normal rat chow), alcohol (20 %) fed diabetic (HFD+STZ), and pre-diabetic rats (HFD alone). After, two months of the experimental period, blood and liver tissues were collected lipid metabolic alteration, liver injury, and fibrosis were determined following biochemical and histological methods. Data were analyzed using one-way ANOVA and Dunnett's Post Hoc test. Significant dyslipidemia was observed in the liver tissues of diabetic and pre-diabetic rats following alcohol ingestion. A significant (p<0.05) increase in lipid peroxidation status, and hepatic marker enzyme activities (p<0.0001) were observed in diabetic animals. In corroborating with these observations, hematoxylin and eosin staining of hepatic tissue revealed the presence of sinusoidal dilation along with heavily damaged hepatocytes and inflammatory cell infiltration. Further, significantly (p<0.001) increased hepatic hydroxyproline content and extended picrosirius red stained areas of collagen in liver tissue indicated initiation of fibrosis in alcohol-fed diabetic rats. Overall, the results indicate that alcohol consumption in T2DM conditions is more deleterious than pre diabetic conditions in progressing to hepatic fibrosis.

The effect of long-term magnesium treatment on changes in hepatic autophagic and apoptotic ability of type 2 diabetic female rats and their offspring

AimWe investigated the role of magnesium sulfate (MgSO4) and insulin administration on improved autophagy and apoptosis to prevent diabetes in high-fat diet (HFD)-diabetic parents and their offspring. MethodsA HFD and a low dose of streptozotocin (STZ) were used to induce diabetes. Animals were assigned to four groups: non-diabetic control (NDC), diabetic control (DC), the diabetic group received insulin (INS), and the diabetic group received magnesium (MG). The duration of the research was 6 months, and offspring were fed a normal diet for 4 months. Blood glucose was determined weekly in rats (parents and offspring). The gene expression of adenosine monophosphate-activated protein kinase (AMPKα1), Bcl-2-interacting myosin-like coiled-coil protein (Becline-1), P62, Microtubule-associated protein 1 light chain 3 (LC3-II), and caspase-9 of liver tissues were assessed using Real-time PCR. ResultThe analysis of maternal gene expression data showed that treatment with MG and INS considerably augmented the AMPKα1 and LC3-II genes expression and diminished P62 and caspase-9 expression. Also, a significant decrease in the expression of AMPKα1, LC3-II, P62, and Becline-1 was observed in the female offspring in the MG and INS groups. Significant alterations in levels of AMPKα1, Beclin-1, P62, and caspase-9 mRNA were not observed between groups in male offspring, but the expression of LC3-II considerably diminished in the groups compared with the DC group. DiscussionOur data demonstrated that MG supplementation strengthened the mother's autophagy and reduced the transmission of damage to the female offspring. In the male offspring, the transmission of damage was generally less, and MG improved the autophagy condition in the male offspring. Our findings support the presence of a link between autophagy induction and MG-modified biomaterials and determine a potential mechanism of MG-mediated diabetes and autophagy.

Changes in the hippocampal level of tau but not beta-amyloid may mediate anxiety-like behavior improvement ensuing from exercise in diabetic female rats

BackgroundIn the present study, we investigated the effect of high-intensity interval training (HIIT) on cognitive behaviors in female rats with a high-fat diet + streptozotocin (STZ)-induced type 2 diabetes.MethodsTwenty-four female rats were divided into four groups randomly (n = 6): control (C), control + exercise (Co + EX), diabetes mellitus (type 2) (T2D), and diabetes mellitus + exercise (T2D + EX). Diabetes was induced by a two-month high-fat diet and a single dose of STZ (35 mg/kg) in the T2D and T2D + EX groups. The Co + EX and T2D + EX groups performed HIIT for eight weeks (five sessions per week, running on a treadmill at 80–100% of VMax, 4–10 intervals). Elevated plus maze (EPM) and open field test (OFT) were used for assessing anxiety-like behaviors, and passive avoidance test (PAT) and Morris water maze (MWM) were applied for evaluating learning and memory. The hippocampal levels of beta-amyloid (Aβ) and Tau were also assessed using Western blot.ResultsAn increase in fasting blood glucose (FBG), hippocampal level of Tau, and a decrease in the percentage of open arm time (%OAT) as an index of anxiety-like behavior were seen in the female diabetic rats which could be reversed by HIIT. In addition, T2D led to a significant decrease in rearing and grooming in the OFT. No significant difference among groups was seen for the latency time in the PAT and learning and memory in the MWM.ConclusionsHIIT could improve anxiety-like behavior at least in part through changes in hippocampal levels of Tau.

Protective Effect of Betulin on Streptozotocin-Nicotinamide-Induced Diabetes in Female Rats.

Type 2 diabetes is characterized by hyperglycemia and a relative loss of β-cell function. Our research investigated the antidiabetic potential of betulin, a pentacyclic triterpenoid found primarily in birch bark and, intriguingly, in a few marine organisms. Betulin has been shown to possess diverse biological activities, including antioxidant and antidiabetic activities; however, no studies have fully explored the effects of betulin on the pancreas and pancreatic islets. In this study, we investigated the effect of betulin on streptozotocin-nicotinamide (STZ)-induced diabetes in female Wistar rats. Betulin was prepared as an emulsion, and intragastric treatments were administered at doses of 20 and 50 mg/kg for 28 days. The effect of treatment was assessed by analyzing glucose parameters such as fasting blood glucose, hemoglobin A1C, and glucose tolerance; hepatic and renal biomarkers; lipid peroxidation; antioxidant enzymes; immunohistochemical analysis; and hematological indices. Administration of betulin improved the glycemic response and decreased α-amylase activity in diabetic rats, although insulin levels and homeostatic model assessment for insulin resistance (HOMA-IR) scores remained unchanged. Furthermore, betulin lowered the levels of hepatic biomarkers (aspartate aminotransferase, alanine aminotransferase, and alpha-amylase activities) and renal biomarkers (urea and creatine), in addition to improving glutathione levels and preventing the elevation of lipid peroxidation in diabetic animals. We also found that betulin promoted the regeneration of β-cells in a dose-dependent manner but did not have toxic effects on the pancreas. In conclusion, betulin at a dose of 50 mg/kg exerts a pronounced protective effect against cytolysis, diabetic nephropathy, and damage to the acinar pancreas and may be a potential treatment option for diabetes.

Abstract TMP117: Exposure to Single or Recurrent Hypoglycemia Increases Stroke Risk in Insulin-Treated Female Diabetic Rats

Stroke is a serious complication of diabetes. Intensive treatment of diabetes increases the risk of recurrent hypoglycemia (RH). Hypoglycemia exposure causes prothrombotic effects. Earlier, we demonstrated that exposure to single hypoglycemia (SH), 5-day RH (once every day), and twice-a-week RH for 6 weeks increases stroke risk in male insulin-treated diabetic (ITD) rats. In the present study, we determined the effect of SH and RH on stroke risk/thrombosis in female rats. Streptozotocin diabetic female rats were treated for hyperglycemia using insulin pellets (Figure A). Rats were randomly assigned to either hyperinsulinemic euglycemia (ITD+RH+Glucose, control) or hyperinsulinemic hypoglycemia (ITD+RH) groups (3 h duration) (Figure B). Separate groups tested the effect of SH, RH for 5 days, or RH for 6 weeks. Based on the results of the male studies, stroke risk after SH, 5-day RH, and 6-week RH were assessed on days 1, 7, and 3 post-last hypoglycemia, respectively. Groups were balanced (confirmed by Chi square test) in terms of the proportion of animals at different stages of the estrous cycle. To assess the risk of stroke, the carotid artery and jugular vein were linked with a shunt containing a suture, and the weight of the clot accumulated on the suture following 15 min of blood flow was quantified as a measure of stroke risk/thrombosis. The clot weight in the SH-exposed ITD group was significantly higher by 47% (22±3 mg, n=9, p&lt;0.05) when compared to its respective control (15±1 mg, n=8). The clot weight determined 7 days after the 5-day ITD+RH group (18±1 mg, n=7) was significantly (p&lt;0.05) higher than its control group (15±1 mg, n=9). The clot weight in the 6-week ITD+RH group was significantly higher by 47% (20±2 mg, n=9, p&lt;0.01) when compared to its control (14±1 mg, n=7) (Figure C). Our results show that similar to male rats, SH and RH increase stroke risk in female ITD rats. We are currently evaluating the underlying mechanisms. Acknowledgment: NIH (NS122808).

Anti-diabetic impact of ‘Aju Mbaise’ herbal cocktail in streptozotocin-induced diabetic female rats

This study evaluated the hypoglycaemic potential of ‘Aju Mbaise’ herbal mixture. Female Wistar rats of 40 – 50 g and fifty-four (54) in number were obtained and housed at the animal house of the Department of Pharmacology, University of Port Harcourt. They were assembled into 6 groups of 9 rats each. Group I served as the normal control (NC) while the remaining five groups were induced with diabetes type 2 using high-fat diet (HFD) for about 8 weeks and streptozotocin at 35 mg/kg body weight. Group II was the diabetic control (DC) while the other groups (III, IV, V &amp; VI) were administered 7.2 mg/kg metformin and the cocktail extract at three different concentrations of 500 mg/kg, 250 mg/kg, and 100 mg/kg respectively. Biochemical tests were conducted after twelve weeks of treatment. The blood glucose concentration was estimated using the Accu-check glucometer and glucose strips while the rest biomarkers were analyzed using their specific test kits. Diabetes mellitus was confirmed after HFD and STZ administration. Result obtained showed that the normal and metformin control groups recorded significant (p&lt;0.05) lower blood glucose, liver enzymes (AST, ALT, &amp; ALP), urea, and creatinine, as well as higher total protein concentrations when compared to the diabetic control and treated groups. Also, significant (p&lt;0.05) reduction in blood glucose, liver enzymes, urea, and creatinine, as well as increase in total protein concentrations was recorded by the treated groups when compared to the diabetic control group. This study revealed the potential hypoglycaemic effect of ‘Aju Mbaise’ herbal cocktail.

Sex‐related differences in the visual function of an animal model of type 1 diabetes

Aims/Purpose: Recent basic and clinical research evidence suggests that male–female differences may influence retinal function and structure. It is also well‐established that diabetes affects retinal function. This work aimed to assess whether type 1 diabetes differentially affects neuroretinal function in male and female Wistar rats.Methods: To induce type 1 diabetes, male and female Wistar rats were injected (i.p.) with streptozotocin (65 mg/kg). Electroretinograms (ERGs) were recorded before and 1, 2, and 4 weeks after diabetes induction (n = 12–13 animals/group). To assess the effect of chronic hyperglycemia on the content of molecular components of the blood‐retinal barrier (BRB), specific tight junction proteins were assessed by Western Blotting. Neuroinflammation was evaluated by measuring the retinal levels of pro‐inflammatory cytokines.Results: Some sex‐related changes in retinal function were detected in the diabetic animals. Overall, in male diabetic rats, compared to control male rats, the differences found under scotopic conditions were mainly in the positive scotopic threshold response (pSTR), with decreased amplitudes (at weeks 2 and 4), and higher latencies (at weeks 1 and 4). In contrast, diabetic female rats, compared to control females, presented a higher increase in the latency value of the negative STR (nSTR; at weeks 1 and 4), a‐wave (at weeks 1, 2, and 4), and oscillatory potentials 2, 3, and 4 (at weeks 1, 2, and 4). Under photopic conditions, male diabetic rats showed higher implicit time values of the fundamental flicker wave (at week 4) and a decrease in the amplitude of the flicker 2nd harmonic (at week 4) compared to control males. Conversely, in diabetic female rats, there were no differences in these parameters compared to control female rats. Concerning the BRB and neuroinflammation, no changes were found in diabetic males and females compared to their respective controls.Conclusions: Our findings suggest that type 1 diabetes differentially affects the retinal function in male and female Wistar rats.Support: FCT‐Portugal: PEst UIDB/04539/2020 and UIDP/04539/2020; 2020.07432.BD.

Effects of Bee Bread on Serum Lipid Profile in Alloxan Induced Diabetic Female Rats

Introduction: Diabetes Mellitus (DM) represents one of the most frequent public health problems with increasing prevalence worldwide. This condition is caused by increased hepatic glucose production, lower insulin secretion, and impaired insulin action. Subsequently, the lipid is used as an alternative resource of cellular energy, resulting in abnormalities of lipid metabolism.&#x0D; Aim: To determine effects of Bee Bread on Serum Lipid Profile in Alloxan Induced Diabetic rats&#x0D; Methodology: A total thirty female Sprague-Dawley rats were grouped in to five. Gp1: Non-DM, Gp2: DM Naïve, Gp3: DM + 200BB, Gp4: DM + 400BB and Gp5: DM + Metformin. Animals were induced with DM following single injection of freshly prepared alloxan in normal saline. Animals were treated for three weeks before they were sacrificed using chloroform sedation. Blood samples were collected for Serum Lipid Profile analysis.&#x0D; Results: When compared, Serum TC, TG, and LDL-C were significantly higher in the DM group compared to Non-DM, BB administered and DM + Metformin groups.&#x0D; Reduction in these lipids was achieved with the administration of Bee Bread. HDL-C was significantly lower in the DM group, compared to other groups. The study revealed improvements in serum HDL-C with the administration of Bee Bread.&#x0D; Conclusion: Bee Bread causes reduction in lipids and improves HDL-C in Diabetic Rats.

Risk of endothelial dysfunction in streptozotocin-induced diabetic Sprague-Dawley rats: Nitric oxide in focus

Endothelial dysfunction in diabetes manifests in part as reduction of nitric oxide (NO) bioavailability, which leads to inadequate relaxation of the vascular smooth muscle and a disparity between the vasoconstrictive and vasorelaxant intracellular pathways which favours a rise in vasoconstriction. In this current work, we evaluated serum Nitric oxide (NO) concentration and the activity of Nitric oxide synthase (NOS) in streptozotocin-induced diabetic male and female rats' serum. Our results showed initial and final fasting blood glucose concentration 5.30±0.16mmol/l and 5.24±.015mmol/l versus 5.68±0.18mmol/l and 5.43±0.15mmol/l in male and female controls. Among the diabetic rats, the initial and final fasting blood glucose concentration was 17.50±1.91mmol/l and 15.68±2.84mmol/l versus 20.50±4.76mmol/l and 19.40±4.13mmol/l in male and female rats respectively. NO concentration was 106.12±7.23μmol/l and 131.81±12.54 μmol/l in male and female control rats compared to 52.38±3.01μmol/l and 65.29±16.19 μmol/l in male and female diabetic rats respectively. Serum activity of NOS were 133.72±10.92μIU/l and 156.06±18.22 μIU/l in control male and female rats compared to 98.01±1.48 μIU/l, 78.89±8.39μIU/l in diabetic male and female rats respectively. The difference in both NO concentration and NOS activity was significant between diabetics and non-diabetic rats as well as between male and female diabetics rats (p&lt; 0.05). The endothelial dysfunction in diabetic animals regardless of gender may be an initial pointer to upcoming pathogenesis and we recommend routine evaluation of NO concentration and NOS activities among diabetics.

Protective effect of soy isolate protein against streptozotocin induced gestational diabetes mellitus via TLR4/MyD88/NF-κB signaling pathway

BackgroundGestational diabetes mellitus (GDM) is a serious complication of pregnancy that is characterized by high blood sugar levels that occur due to insulin resistance and dysfunction in glucose metabolism during pregnancy. It usually develops in the second or third trimester of pregnancy and affects about 7 % of all pregnancies worldwide. In this experimental study, we scrutinized the GDM protective effect of soy isolate protein against streptozotocin (STZ) induced GDM in rats and explore the underlying mechanism. Material and methodsSprague-Dawley (SD) rats were used in this experimental study. A 55 mg/kg intraperitoneal injection of streptozotocin (STZ) was administered to induce diabetes in female rats, followed by oral administration of soy isolate protein for 18 days. Body weight, glucose levels, and insulin were measured at different time intervals (0, 9, and 18 days). Lipid profiles, antioxidant levels, inflammatory cytokines, apoptosis parameters, and mRNA expression were also assessed. Pancreatic and liver tissues were collected for histopathological examination during the experimental study. ResultsSoy isolate protein significantly (P < 0.001) reduced the glucose level and enhanced the insulin level and body weight. Soy isolate protein remarkably decreased the placental weight and increased the fetal weight. Soy isolate protein significantly (P < 0.001) decreased the HbA1c, hepatic glycogen, serum C-peptide and increased the level of free fatty acid. Soy isolate protein significantly (P < 0.001) altered the level of lipid, antioxidant and inflammatory cytokines. Soy isolate protein significantly (P < 0.001) improved the level of adiponectin, visfatin and suppressed the level of leptin and ICAM-1. Soy isolate protein significantly (P < 0.001) altered the mRNA expression and also restored the alteration of histopathology. ConclusionBased on the result, soy isolate protein exhibited the GDM protective effect against the STZ induced GDM in rats via alteration of TLR4/MyD88/NF-κB signaling pathway.

Diabetic rats: Hyperlipidemia and role of mango seed

&lt;b&gt;Background:&lt;/b&gt; Diabetes is a hyperglycemic disease caused by a lack of action of insulin, but serum lipids are also strongly affected by insulin. Serum lipid abnormalities (dyslipidemia) are frequently observed in diabetic populations regardless of insulin deficiency or insulin resistance. Hypertriglyceridemia is the greatest common serum lipid abnormality in diabetic populations. To study the effect of mango seeds on dyslipidemia in diabetes-induced rats. There was a noticeable difference in the body weight (BW) of male and female diabetic rats.&lt;br /&gt; &lt;b&gt;Materials and methods:&lt;/b&gt; To investigate effect on BW and the antihyperlipidemic actions of ethanolic extract of mango seed (EEMS) on alloxan-mediated diabetic Sprague-Dawley rats. Antihyperlipidemic in addition antidiabetic properties of an EEMS was planned at 100 and 200 mg/kg BW. The antidiabetic effect of EEMS been matched with tolbutamide 500 mg/kg BW. The lipid levels and BW of male and female rats were examined at consistent periods throughout the research.&lt;br /&gt; &lt;b&gt;Results:&lt;/b&gt; The outcomes displayed that the dyslipidemia was considerably decreased in the different treatment groups, while matched with control, the animals cured with tolbutamide and EEMS control.&lt;br /&gt; &lt;b&gt;Conclusion:&lt;/b&gt; EEMS exhibited a noteworthy antihyperlipidemic actions in addition with marked difference on BW of both male and female in alloxan-induced diabetic rats.

Modulatory role of Coriandrum sativum (coriander) extract against diabetic complications on the gonads of female rats and their offspring

It is well known that diabetes is associated with impairment of ovarian and testicular structure and function. Coriander (Coriandrum sativum L.) is identified as one of the oldest herbal plants valued for its nutritional and medicinal properties. This work is mainly designed to evaluate the possible modulatory role of dry coriander fruit extract against gonadal impairments associated with diabetes in female rats and their pups. Twenty-four pregnant rats were divided into four groups (n = 6): group I served as control, group II was administered daily with coriander fruit extract (250 mg/kg b.wt), group III was injected interaperitoneally with a single dose of streptozotocin (STZ) (80 mg/kg b.wt), and group IV was injected with single dose of STZ and post administered coriander extract. The experiment was conducted from the 4th day of gestation till the end of weaning. At the end of the experiment, the mothers’ rats and their offspring were weighed, sacrificed, the ovaries from mothers as well as ovaries and testes from offspring were immediately excised, and processed for histological, immunohistochemical and evaluation of apoptosis and transforming growth factorβ (TGF-β). Also, blood samples were collected and analyzed to estimate the levels of sex hormones as well as antioxidants.In STZ induced diabetes in mother's rats and their offspring, the ovarian sections revealed severe histopathological signs included several atretic follicles, dilated and congested blood capillaries. Additionally, the testicular sections of offspring appeared with destructive seminiferous tubules. Immunohistochemically, the ovarian sections displayed weak to negative expression for calretinin marker however the testicular sections showed strong expression for Bax protein (apoptotic marker) and weak to negative expression for Ki67 protein (proliferative marker). Also, the mean % values of positively expressed cells for TGF-β and annexin-v markers (late and early apoptosis indicator) were significantly elevated in the ovarian and testicular tissues of STZ-induced group of mother's rats and their pups if compared with control. Further results revealed that the levels of insulin, FSH, LH, estrogen, SOD and CAT were significantly decreased if compared with control however the levels of MDA and NO were significantly elevated. Administration of coriander fruit extract to diabetic rats successfully alleviated most of the altered histological, immunohistochemical, biochemical, and apoptotic changes induced by diabetes. Coriandrum sativum fruit extract has a powerful ameliorative role against STZ-induced diabetic gonadal dysfunctions in female rats and their offspring.

The Effects of Resveratrol and Melatonin on Cardiac Dysfunction in Diabetic Elderly Female Rats

We aimed to investigate the effects of melatonin and resveratrol on diabetes-related papillary muscle dysfunction and structural heart disorders. The protective effect of resveratrol and melatonin supplementation on cardiac functions was investigated in a diabetic elderly female rat model. 16-month-old rats (n=48) were allocated into 8 groups. Group1: Control, Group2: Resveratrol Control, Group3: Melatonin Control, Group4: Resveratrol and Melatonin Control, Group5: Diabetes, Group6: Diabetes Resveratrol, Group7: Diabetes Melatonin, Group8: Diabetes Resveratrol and Melatonin. Streptozotocin was injected intraperitoneally to the rats for experimental diabetes induction. Thereafter, resveratrol (intraperitoneal) and melatonin (subcutaneous) were administered for 4 weeks. Resveratrol and melatonin had a protective effect on the contractile parameters and structural properties of the papillary muscle, which was impaired by diabetes. it has been presented that diabetes impairs the contractile function of the papillary muscle for each stimulus frequency tested and the responses obtained as a result of Ca+2 uptake and release mechanisms from the Sarcoplasmic reticulum, and it has been observed that these effects are improved with resveratrol and melatonin injection. The decrease in myocardial papillary muscle strength in the diabetic elderly female rat can be reversed with the combination of resveratrol, melatonin and resveratrol+melatonin. Melatonin+resveratrol supplementation is no different from melatonin and/or resveratrol supplementation. Resveratrol and melatonin supplementation may have a protective effect on cardiac functions in a diabetic elderly female rat model.

Melatonin protects retinal tissue damage in streptozotocin-induced aged rats

ObjectivesThe aim of this study was to investigate how melatonin administration affects retinal oxidative damage and retinal SIRT1 gene activation in diabetic elderly female rat model. Methods16-months-old female rats were used in the study. A total of 24 rats were divided into 4 groups in equal numbers: Group 1. Control, Group 2. Control + Melatonin, Group 3. Diabetes, Group 4. Diabetes + Melatonin. In group 3 and 4 rats, diabetes was induced by intraperitoneal (IP) injection of streptozotocin. Groups 2 and 4 were given ip melatonin for 4 weeks. SIRT-1 gene expression was determined by PCR method and GSH and MDA levels by ELISA in retinal tissue samples taken from animals sacrificed under general anesthesia. ResultsIn our study, the highest retinal SIRT1 expression values were obtained in the diabetes + melatonin (G4) group. The retinal SIRT1 expression values of the diabetes group (G3) were lower than group 4 and higher than the general control (G1) and control + melatonin (G2) groups. Again in our study, the highest retinal MDA values were obtained in the diabetes group (G3). The highest retinal GSH values were obtained in the Diabetes + melatonin group (G4). ConclusionThe results of our study showed that melatonin supplementation has a protective effect on retinal tissue in a diabetic elderly female rat model. This protective effect of melatonin supplementation occurs by increasing both retinal antioxidant activity and retinal SIRT1 gene expression.

PROPERTIES OF FATIGUE BETWEEN SLOW AND FAST MUSCLES OF MALE AND FEMALE DIABETIC RATS

Background: The metabolic disorder of Type 2 Diabetes Mellitus (T2DM) has deleterious effects on skeletal muscle contractile functions. This study aimed to compare parameters of fatigue between slow and fast skeletal muscles of male and female type 2 diabetic Sprague-Dawley rats. Methodology: This was a quasi experimental study conducted at Army Medical College Rawalpindi and National Institute of Health, Islamabad. Forty Sprague Dawley rats in good health were split into groups I (Control) and II (Diabetics) of 20 rats each. Each group had 10 male and 10 female rats. Diabetic groups were given intra-peritoneal streptozotocin (STZ), 35 mg/Kg body weight on 15th day. Control groups were fed a normal diet and diabetic rats were given diet with high fat. On 21st day body weight, blood glucose and triglyceride/high density lipoprotein ratio were estimated to confirm extraction of type 2 diabetes mellitus. Intact Soleus and Extensor Digitorium Longus muscles were removed and fixed in organ bath system having Krebs-Ringer buffer solution and connected to data acquisition unit (iWorx®) to study their fatigability parameters. Independent samples t-test was used for statistical analysis. Results: Slow and fast skeletal muscles in diabetic rats showed reduction in resistance to and recovery from fatigue. Fatigue parameters between male and female diabetic rats revealed no significant differences. Conclusion: Fatigue parameters do not differ between male and female diabetic rats. Pak J Physiol 2023;19(1):7?10

Abstract 108: Stroke Amplifies Cerebrovascular Matrix Metalloproteinase-3 (MMP3) Activity In Diabetes: Potential Sex Differences And Impact On Endothelial To Mesenchymal Transition (EndMT)

Both female sex and diabetes increase the risk of poor stroke recovery, but underlying mechanisms are unclear. We reported that inhibition of MMP3 with UK356618 prevents hemorrhagic transformation (HT) in male diabetic rats, and female diabetic rats develop greater HT than males. Emerging evidence suggests that MMP3 may contribute to the regulation of EndMT, a process associated with scarring and impaired healing. We tested the hypotheses that: 1) MMP3 activity is amplified to a greater extent in the cerebrovasculature of female diabetic rats, especially after stroke; 2) EndMT occurs in female brain endothelial cells (BMVECs), and 3) MMP3 inhibition in stroke and diabetes-like conditions improves cell integrity/survival in female BMVECs. Methods: Cerebral microvascular homogenates were prepared from control and diabetic male and female rats subjected to sham or 60-min middle cerebral artery occlusion. MMP3 expression/activity was measured. EndMT /endothelial integrity were assessed by immunoblotting in male and female BMVECs cultured in normal, diabetes or ischemia-like conditions. Results (Table): Cerebrovascular MMP3 expression/activity is higher in females. TGF-β, a major EndMT inducer, significantly decreased VE-Cadherin and increased EndMT markers αSMA and p-SMAD2 to a greater extent in female cells. Ongoing studies suggested that MMP3 inhibitor UK356618 improved the expression of tight junction protein occludin and cell survival, which was associated with a decrease in transforming growth factor receptor-1 (TGFβR1). Conclusions: The impact of long-term MMP3 inhibition on EndMT, neurovascular restoration, and post-stroke recovery in females and diabetes needs to be further explored.