Streptozotocin-induced Diabetic Male Rats Research Articles

Effects of Carica Papaya and Psidium Guajava Extracts on Hepato-Renal Performance of Streptozotocin-Induced Diabetic Male Albino Rats

The growing number of diabetes coupled with the harsh side effects of some synthetic drugs has led to the increasing search for alternative medicine which are relatively cheap with minimum side effects. Objective: To investigate the anti-diabetic effect of ethanolic extract of Carica papaya and Psidium guajava extracts separately and in combination, and the effect of treatment on hepato-renal performance. Methods: Papaya and guava leaves were macerated in 98% ethanol for extraction. Results: The result showed that ethanolic leaf extract of P. guajava and C. papaya significantly (P< 0.05) reduced blood glucose level, Total Cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL) and significant increase in high density lipoprotein (HDL) as compared to diabetic control group. Serum activities of liver enzymes such as aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) was slightly elevated that indicate hepatotoxic nature of plant extracts. The level of gamma-glutamyl transferase (GGT), bilirubin and HbA1C level were restored to normal range. A slight reduction in body weight (P>0.05) of treated groups was observed. Serum urea and creatinine concentration was restored to normal level in treated rats with regeneration of kidney function. Conclusions: The study concluded that individual and combined plant extract show anti-hyperglycemic effect but the combined remedy at this dose show hepatotoxicity.

Antioxidant Activity of the Ethyl Acetate Extract of Potentilla indica on Kidneys of Streptozotocin‐Induced Diabetic Rats

Diabetes mellitus is a chronic-degenerative disease characterized by chronic hyperglycemia. This condition may lead to an increase of the oxidative stress, which contributes to the development of diabetes complications including diabetic kidney disease. Several studies have addressed the antioxidant effects of a wide range of plant extracts in the treatment of diabetes. Potentilla indica is a traditional herbal medicine in Asia, employed in the treatment of several diseases including diabetes, due to its secondary metabolites with bioactive functions such as antioxidant activity. Therefore, we hypothesize that the ethyl acetate extract of Potentilla indica decreases the oxidative stress on kidneys of streptozotocin-Induced diabetic rats improving the diabetic condition. Objective The present study aimed to investigate the antioxidant activity of the ethyl acetate extract of Potentilla indica on kidneys of streptozotocin-induced diabetic male rats. Methods In this research we assessment the antioxidant activity of the ethyl acetate extract of Potentilla indica by employing in vitro assays to measure its protective effect on lipid peroxidation and ferric reducing antioxidant power. We also tasted the extract in male Wistar rats (300-350 g), which were randomly divided into 4 groups: normoglycemic control, diabetic control, normoglycemic treated with the extract and diabetic treated with the extract. All groups were administered orally once daily for 60 days with the vehicle for the control groups and with the ethyl acetate extract of P. indica (25 mg/Kg) for the treated groups, respectively. After 60 days of treatment, rats were euthanized to obtain homogenate and mitochondria of kidney, which were used for the determination of mitochondrial respiratory chain complex activities, reactive oxygen species (ROS) production, lipid peroxidation and catalase activity. Results The ethyl acetate extract of Potentilla indica possessed in vitro antioxidant activity at different concentrations in contrast with Trolox as positive control. Furthermore, in the treated diabetic group, the extract reduced lipid peroxidation, ROS production, and restored mitochondrial respiratory chain complexes and catalase activities when compared with diabetic control group. Conclusion Our data suggest that the ethyl acetate extract of Potentilla indica possessed both in vitro as in vivo antioxidant activity on kidneys of streptozotocin-induced diabetic rats.

Leaf extracts of Glyphaea brevis attenuate high blood glucose and lipids in diabetic rats induced with streptozotocin

Background: Diabetes is a non-communicable disease causing impairment of carbohydrate and lipid metabolisms. Previous ethnobotanical surveys showed that leaves of Glyphaea brevis (G. brevis) are used conventionally in the treatment of diabetes with limited scientific evidence. Objective: We aimed to determine the effects of aqueous (AE) and hydroethanolic extracts (HEE) of G. brevis leaves in attenuating diabetes-linked hyperglycemia and hyperlipidemia in an animal model. Materials and Methods: Thirty streptozotocin-induced diabetic male rats were divided into six groups receiving the following daily treatments for 4 weeks orally: control (distilled water), reference (tolbutamide 80 mg/kg) and 4 tests (AE 250 mg/kg, AE 500 mg/kg, HEE 250 mg/kg, and HEE 500 mg/kg). The effects of each treatment on postprandial hyperglycemia were assessed using oral glucose tolerance and oral starch tolerance tests. Blood was collected to assess the effects of treatments on fasting plasma glucose, glycated hemoglobin (HbA1c), and lipid profile. Liver glycogen and gluconeogenic enzyme activity were also measured. Results: AE- and HEE-treated rats had 36%–64% lower fasting blood glucose levels, 34%–73% lower postprandial glycemia, and 15%–75% lower HbA1c than rats from control group (P

Lactucaxanthin protects retinal pigment epithelium from hyperglycemia-regulated hypoxia/ER stress/VEGF pathway mediated angiogenesis in ARPE-19 cell and rat model

Hyperglycemia mediated perturbations in biochemical pathways induce angiogenesis in diabetic retinopathy (DR) pathogenesis. The present study aimed to investigate the protective effects of lactucaxanthin, a predominant lettuce carotenoid, on hyperglycemia-mediated activation of angiogenesis in vitro and in vivo diabetic model. ARPE-19 cells cultured in 30 mM glucose concentration were treated with lactucaxanthin (5 μM and 10 μM) for 48 h. They were assessed for antioxidant enzyme activity, mitochondrial membrane potential, reactive oxygen species, and cell migration. In the animal experiment, streptozotocin-induced diabetic male Wistar rats were gavaged with lactucaxanthin (200 μM) for 8 weeks. Parameters like animal weight gain, feed intake, water intake, urine output, and fasting blood glucose level were monitored. In both models, lutein-treated groups were considered as a positive control. Hyperglycemia-mediated angiogenic marker expressions in ARPE-19 and retina of diabetic rats were quantified through the western blot technique. Expression of hypoxia, endoplasmic reticulum stress markers, and vascular endothelial growth factor were found to be augmented in the hyperglycemia group compared to control (P < 0.05). Hyperglycemia plays a crucial role in increasing cellular migration and reactive oxygen species besides disrupting tight junction protein. Compared to lutein, lactucaxanthin aids retinal pigment epithelium (RPE) function from hyperglycemia-induced stress conditions via downregulating angiogenesis markers expression. Lactucaxanthin potentiality observed in protecting tight junction protein expression via modulating reactive oxygen species found to conserve RPE integrity. Results demonstrate that lactucaxanthin exhibits robust anti-angiogenic activity for the first time and, therefore, would be useful as an alternative therapy to prevent or delay DR progression.

A study of the aphrodisiac properties of Cordyceps militaris in streptozotocin-induced diabetic male rats.

Background and Aim:Cordyceps militaris (CM) is a fungus that has been used to enhance aphrodisiac activity in men, but to date, no studies have focused on its antidiabetic properties. This study aimed to investigate the effects of CM on reproductive performance of streptozotocin (STZ)-induced diabetic male rats.Materials and Methods:Six-week-old Wistar rats were randomly divided into four groups: control Group 1 consisting of healthy rats; Group 2, healthy rats treated with CM (100 mg/kg); Group 3, diabetic untreated rats; and Group 4, diabetic rats treated with CM (100 mg/kg). Rats were orally administered with vehicle or CM for 21 days. The body weight, blood glucose level, food intake, epididymal sperm parameter, sexual behavior, serum testosterone level, and antioxidant parameters were determined.Results:The results indicated that CM treatment in STZ-induced diabetic rats significantly improved the epididymal sperm parameter and serum testosterone level and, in turn, their copulatory behavior. CM treatment in diabetic rats significantly ameliorated malondialdehyde level and significantly improved the glutathione and catalase levels.Conclusion:These results provide new information on the pharmacological properties of CM in ameliorating testicular damage due to oxidative stress and improving sexual performance in diabetic male rats.

Kigelia Africana Stem Bark Extract Treatment Reverses Type 1 Model of Experimental Diabetes and Associated Reproductive Impairments in Male Wistar Rats

A key hallmark in diabetes is altered reproductive functions. Kigelia africana is reported to offer therapeutic influence in diabetes. However, literature offers nothing concerning its ability to reverse reproductive complications of diabetes. This study investigates the effect of the ethanolic extract of Kigelia africana (EEKA) on reproductive functions in streptozotocin-induced diabetic male rats. Thirty adult male Wistar rats (150-200 g) were randomly divided into five groups; Group 1 (control) received distilled water (vehicle). Group 2 was treated with 250 mg/kg EEKA. Groups 3, 4, and 5 were made diabetic using streptozotocin. Thereafter, groups 4 and 5 were treated with 250 mg/kg EEK and glibenclamide respectively. Treatments were by oral gavage for six weeks. Bodyweight and blood glucose, liver enzymes and proteins, superoxide dismutase (SOD), malondialdehyde activity (MDA), testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), sperm count, and motility was assessed. EEKA treatment significantly reduced blood glucose in diabetic rats. Serum testosterone was significantly reduced in the diabetic group. However, treatment with EEKA significantly modulated the reduction. EEKA treatment in diabetic rats significantly increased serum LH. Therapeutic EEKA treatment in diabetic rats significantly reversed reduced sperm count and motility. EEKA treatment in the diabetic group reduced MDA activity while significantly enhancing SOD activity. The significant increases in serum alanine aminotransferase and aspartate aminotransferase were significantly reduced with EEKA treatment in the diabetic group. Total protein and albumin were significantly reduced in the diabetic group but significantly reversed with EEKA treatment. Therapeutic administration of EEKA reduced hyperglycemia, enhanced sperm count, motility, and serum testosterone levels in diabetic rats. Phytochemical constituents and robust antioxidant activity of EEKA is involved in the modulation and reversal of diabetes and impaired reproductive parameters.

α-Lipoic Acid Increases Collagen Synthesis and Deposition in Nondiabetic and Diabetic Rat Kidneys.

α-Lipoic acid (ALA) is widely used as a nutritional supplement and therapeutic agent in diabetes management. Well-established antioxidant and hypoglycemic effects of ALA were considered to be particularly important in combating diabetic complications including renal injury. The present study evaluated the potential of ALA to affect profibrotic events in kidney that could alter its structure and functioning. ALA was administered intraperitoneally (10 mg/kg) to nondiabetic and streptozotocin-induced diabetic male Wistar rats for 4 and 8 weeks. The effects of ALA were assessed starting from structural/morphological alterations through changes that characterize profibrotic processes, to regulation of collagen gene expression in kidney. Here, we demonstrated that ALA improved systemic glucose and urea level, reduced formation of renal advanced glycation end products (AGEs), and maintained renal structural integrity in diabetic rats. However, profibrotic events provoked in diabetes were not alleviated by ALA since collagen synthesis/deposition and expression of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) remained elevated in ALA-treated diabetic rats, especially after 8 weeks of diabetes onset. Moreover, 8 weeks treatment of nondiabetic rats with ALA led to the development of profibrotic features reflected in increased collagen synthesis/deposition. Besides the TGF-β1 downstream signaling, the additional mechanism underlying the upregulation of collagen IV in nondiabetic rats treated with ALA involves decreased DNA methylation of its promoter that could arise from increased Tet1 expression. These findings emphasize the therapeutic caution in the use of ALA, especially in patients with renal diabetic complication.

High dietary salt intake alleviates fasting blood glucose in streptozotocin-induced diabetic male Wistar rats

High dietary salt intake alleviates fasting blood glucose in streptozotocin-induced diabetic male Wistar rats

Effects of Cultured Cordycep militaris on Sexual Performance and Erectile Function in Streptozotocin-Induced Diabetic Male Rats.

Cordyceps militaris (CM), a valuable edible and medicinal fungus, has been used as traditional medicine to treat health conditions, as well as hyposexuality in Asian societies for over a century. Due to the high demand, several artificial cultivation methods have been developed for their biological activities. In this study, CM was cultured on medium that contained white rice and silkworm pupae, and the levels of cordycepin and adenosine, as well as its aphrodisiac effects in diabetes-induced erectile dysfunction (DIED), were evaluated. Diabetic rats were induced by streptozotocin (STZ) injection and administered orally with CM (0.1, 0.5, and 1.0 g/kg BW/day) for 3 weeks. Diabetic rats in negative and positive control groups received vehicle and sildenafil citrate (5 mg/kg), respectively. Results showed the changes in mating behaviour in which mount latency and intromission latency were significantly increased in diabetic rats, compared with the normal control group. Diabetic rats also showed a significant reduction in intracavernosal pressure (ICP) response to cavernous nerve stimulation, sperm count, testosterone level, penile nitric oxide synthase (NOS), and testicular superoxide dismutase (SOD) activities, when compared to the normal control group. Administration of CM (0.1, 0.5, and 1.0 g/kg BW/day) reversed the effects of diabetes on the mating behaviour, and the ICP responses to electrical stimulation. Moreover, the levels of penile NOS, testicular SOD activities, testosterone, and sperm count were significantly increased, and testicular malondialdehyde (MDA) levels were significantly decreased in these treated diabetic rats. Diabetic rats treated with sildenafil showed a significant induction in intromission frequency and NOS and SOD activities, as well as a marked increase in ICP responses. These results suggest that CCM exerts its aphrodisiac effect, possibly through activating testosterone production and suppressing oxidative stress to enhance erectile function in diabetic rats.

ANNONA MURICATA LINN. ETHANOLIC LEAF EXTRACT AMELIORATES REPRODUCTIVE COMPLICATIONS IN STREPTOZOTOCIN-INDUCED DIABETIC WISTAR RATS

Diabetes mellitus is an endocrine and metabolic disorder of humans and animals characterized by hyperglycemia and low blood insulin levels or insensitivity of target organs to insulin and it’s a major health problem affecting patient’s quality of life due to its many complications. Infertility is one of the major secondary complications in diabetes. Although numerous drugs have been used for intervention studies on diabetes-induced infertility worldwide, there are currently no treatments for diabetes associated infertility in humans. This study was performed to investigate the effects of Annona muricata ethanolic leaf extract (AMELE) on fertility of male diabetic rats and levels of blood glucose. Twenty male Wistar rats (150-200g) were randomly distributed into 4 groups (n=5) treated thus: CTRL (control), DNT, DT1 and DT2 (diabetic, single intraperitoneal injection, streptozotocin, 60 mg/kg). Group DT1 and DT2 received AMELE orally at 100 mg/kg and 200 mg/kg respectively daily for fourteen days. Data were analysed using ANOVA at α0.05. The animals were sacrificed after 2 weeks via thiopental injection and testicular weights were recorded. Fasting blood glucose was determined using a digital glucometer. Sperm count, motility, viability and morphology were assessed microscopically. Testes were histologically evaluated. The results showed that oral administration of AMELE at 100 mg/kg and 200 mg/kg to diabetic male rats for fourteen days significantly decreased blood glucose level and also ameliorated diabetes-induced decreases in sperm functions in streptozotocin-induced diabetic male rats.&#x0D; &#x0D;

Aqueous extract of Azadirachta indica leaves favorably alters the course of streptozotocin-induced diabetes in rats: A comparative prospective cohort study

Introduction: Azadirachta indica (neem) is one of the plants commonly used in African traditional medicine for the treatment and management of diabetes mellitus. The present study was undertaken to evaluate the effect of aqueous extract of A. indica leaves on hematology, lipid profile and organ-system function of streptozotocin-induced diabetic male rats.&#x0D; Methods: Thirty albino rats of Wistar strain, weighing between 120 and 150 g, were randomly divided into 6 groups (A-F) and used for the study. Group A was used as a healthy normal control. Groups B-F were induced with diabetes using 50 mg/kg bodyweight (bw.) of streptozotocin. Group B was diabetic untreated; Group C was treated with 100 mg/kg bw. metformin; Groups D to F were treated with 100, 200 and 400 mg/kg bw. of the aqueous extract, respectively. The treatment was carried out daily for a period of 28 days. At the end of the experimental period, the hematological parameters were analyzed using auto haematology analyser. Lipid profiles and histopathological investigations were performed using standard methods.&#x0D; Results: The results obtained showed that aqueous extract of A. indica significantly (p &lt; 0.05) increased the hemoglobin concentration, packed cell volume, red blood cell count, and platelet count of the streptozotocin-induced diabetic rats compared with those of the diabetic-untreated rats. The mean hemoglobin concentrations for groups A, B, C, D, E and F were 11.78, 8.200, 15.18, 13.88, 14.03 and 14.93, respectively. Treatment with the graded doses of the aqueous extract of A. indica significantly (p &lt; 0.05) reduced the total cholesterol, low-density lipoprotein cholesterol, triglycerides and very-low-density lipoprotein, compared with those of the diabetic-untreated control. Treatment also significantly (p &lt; 0.05) increased the high-density lipoprotein cholesterol (HDL-c), compared with that of the control. The mean HDL-c concentration for groups A, B, C, D, E and F were 49.58, 29.79, 40.89, 38.53, 40.40 and 46.54, respectively. The histopathological studies showed regeneration of the pancreas, liver, kidney, heart, brain and lungs for the groups treated with the extract, compared with the diabetic-untreated animals that revealed severe damage to the organ-system functions.&#x0D; Conclusion: These results suggest that the aqueous extract of A. indica can be considered as an excellent remedy for diabetes and a substitute for drugs to reduce complications associated with diabetic conditions.

Phytochemistry and antidiabetogenic property of aqueous extract of Azadirachta indica leaf in streptozotocin-induced diabetic rats

Aim: This study was carried out to determine the phytochemicals and the antidiabetogenic property of Azadirachta indica leaf in streptozotocin-induced diabetic male rats. Methodology: The quantitative phytochemical analysis and the glucose levels were checked using standard methods. Different group of rats were pre-treated for seven, fourteen, twenty-one and twenty-eight days before the induction of diabetes to know the extent of protection the extract will have on the rats by preventing the onset of diabetes. At the end of each treatment period diabetes was induced intraperitoneally using 50mg/kg bodyweight of Streptozotocin. Results: The percentage composition of the phytochemicals in the leaves of Azadirachta indica was as follows: Alkaloids (11.36%), cardiac glycosides (6.19%), flavonoid (5.34%), heamaglutinin (6.331%), oxalate (0.0204%), phenol (4.312%), phytate (4.600%), saponin (12.55%), steroid (0.2566) and tannin (6.17%). The result obtained revealed that there was a better protection for the group of rats pretreated for a period of three weeks and four weeks. The percentage decrease in weight after the induction of diabetes for the groups pre-treated for a period of twenty-one days at varying doses of 100, 200 and 400 mg/kg bodyweight was 6.67%, 6.05% and 4.69% respectively which was significantly (p&lt;0.05) different from the normal untreated group (9.90%). The percentage decrease in weight after the induction of diabetes for the groups pre-treated for a period of twenty-one days at varying doses of 100, 200 and 400 mg/kg bw is 7.04%, 5.97% and 2.50% respectively which was significantly (p&lt;0.05) different from the normal untreated group (10.8%). The percentage increase in the fasting blood glucose level for the groups pretreated for a period of twenty-one days at varying doses of 100, 200 and 400 mg/kg bw was 65.4%, 76.3% and 72.4% respectively which is significantly (p&lt;0.05) different from that of the normal untreated group (82.7%) and the group pre-treated with metformin at a dose of 100 mg/kg bw (84.5%). The percentage increase in the fasting blood glucose level for the groups pre-treated for a period of twenty-eight days at varying doses of 100, 200 and 400 mg/kg bw was 73.5%, 68.5% and 64.4% respectively which was significantly (p&lt;0.05) different from that of the normal untreated group (83.3%) and the group pre-treated with metformin at a dose of 100 mg/kg bw (85.5%). The longer the period of pre-treatment, the better the reduction in the blood glucose levels recorded after the induction of diabetes. Conclusion: These results suggest that the aqueous extract of A. indica leaf has antidiabetogenic effect and could be used in the prevention as well as delaying the onset of diabetes mellitus.

Synthesis, Characterization, and Anti-diabetic Activity of Some Novel Vanadium-Folate-Amino Acid Materials.

A new six intraperitoneal injections insulin-mimetic vanadyl(IV) compounds [(VO)(FA)(AAn)] (where n = 1–6: AA1 = isoleucine, AA2 = threonine, AA3 = proline, AA4 = phenylalanine, AA5 = lysine, and AA6 = glutamine) were synthesized by the chemical reactions between folic acid (FA), VOSO4, and amino acids (AAn) with equal molar ratio 1:1:1 in neutralized media. These complexes were characterized by elemental analysis and estimation of vanadyl(IV) metal ions. The thermal stability behavior of these complexes was studied by TG-DTG-DTA analyses. The structures of these complexes were elucidated by spectroscopic methods like infrared, electron spin resonance (ESR), and solid reflectance spectroscopes. The powder X-ray diffraction (XRD) study suggested the crystalline nature of the complexes. Magnetic moments and electronic spectra revealed the square-pyramid geometrical structure of the complexes. The conductivity results refereed that all synthesized vanadyl(IV) complexes were of a non-electrolyte behavior. The infrared spectra assignments of these complexes revealed that the FAH2 and AAn chelates act as a bidentate ligation. The chelation towards vanadyl (IV) ions existed via deprotonation of one of the carboxylic groups of FAH2 drug ligand, and so amino acids act as bidentate ligands via N-amino and O-carboxylate groups. Both scanning and transmission electron microscope (SEM and TEM) techniques were used to investigate the surface morphology. The main task of this research is the aim of designing a new insulin alternative antidiabetic drug agent. The antidiabetic efficiency of these complexes was evaluated in streptozotocin-induced diabetic male albino rats. Liver and kidney functions, insulin and blood glucose levels, lipid profile, and superoxide dismutase antioxidant (SOD) are verified identifiers for the efficiency of VO(IV)/FA/AAn system compounds as antidiabetic drug agents.

Exogenous Ghrelin Increases Plasma Insulin Level in Diabetic Rats.

Ghrelin, a 28-amino acid peptide, is a strong growth hormone secretagogue and a regulator of food intake. In addition, ghrelin is thought to play a role in insulin secretion and in glucose homeostasis. A lot of contradictory data have been reported in the literature regarding the co-localization of ghrelin with other hormones in the islet of Langerhans, its role in insulin secretion and attenuation of type 2 diabetes mellitus. In this study, we investigate the effect of chronic ghrelin treatment on glucose, body weight and insulin level in normal and streptozotocin-induced diabetic male Wistar rats. We have also examined the distribution pattern and co-localization of ghrelin with insulin in pancreatic islet cells using immunohistochemistry and immune-electron microscopy and the ability of ghrelin to stimulate insulin release from the CRL11065 beta cell line. Control, non-diabetic groups received intraperitoneal injection of normal saline, while treated groups received intraperitoneal injection of 5 µg/kg body weight of ghrelin (amino acid chain 24–51) on a daily basis for a duration of four weeks. Our results show that the administration of ghrelin increases the number of insulin-secreting beta cells and serum insulin level in both normal and diabetic rats. We also demonstrated that ghrelin co-localizes with insulin in pancreatic islet cells and that the pattern of ghrelin distribution is altered after the onset of diabetes. Moreover, ghrelin at a dose of 10−6 M and 10−12 M increased insulin release from the CRL11065 beta cell line. In summary, ghrelin co-localizes with insulin in the secretory granules of pancreatic beta cells and enhances insulin production.

Auricularia Polytricha (Mushroom) Regulates Testicular DNA Expression and Oxidative Stress Markers of Streptozotocin-Induced Diabetic Male Wistar Rat

Local Nigerian men have been using AuriculariaPolytricha as a treatment for sexual dysfunction without supporting evidence from scientific experiments. This study was to investigate the effect of ethanolic extract of A. Polytricha on testicular DNA expression and some oxidative stress markers using STZ-Induced diabetic rats as a model. The experiment included six groups, Group A (Normal Control, treated with normal saline), Group B (treated with 65mg/kg.bw of STZ), Groups C, D, and E (treated with 250mg/kg.bw, 500mg/kg.bw, 1000mg/kg.bw AP after inducing diabetics), and Group F (treated with 40mg/kg.bw metformin after inducing diabetics). The experiment lasted for 35 days. After termination of the experiment, Fuelgen nuclear reaction was used for DNA demonstration to assess testicular DNA distribution while serum Superoxide Dimutase (SOD), Catalase and Melondialdehyde where evaluated using reagent based antioxidant enzyme assay. Results reveals that SOD and Melondialdehyde activities were remarkably (p&lt;0.05) higher in diabetic control animals when compared with the normal control group. Values in Groups C, D and F that were administered with 250, 500mg/kg.bw A. polytricha and metformin respectively were also significantly (p&lt;0.05) increased when compared with the normal control group. However, diabetic animals placed on 1000mg/kg.bw A. polytrichadid not show any statistical significance in comparison with normal control group but was remarkably (p&lt;0.01) decreased when compared to the diabetic group that received low dose A. polytricha, an indication that the reversal is dose dependent. Catalase concentration in diabetic control animals was remarkably (p&lt;0.05) higher when compared to the normal control but was not significantly (p&lt;0.05) different in groups D (DM+500mg/kg.bw A. polytricha) and E (DM+1000mg/kg.bw A. polytricha) when compared with the normal control group. Diabetic control animals showed reduced magenta colour intensity of DNA and increased clustering and cross linking of DNA strands when compared with the normal control. However the degree of cross link in DNA strands was reduced in the diabetic animals placed on 1000mg/kg.bw A. polytrichawhen compared with the diabetic control group. Reversal in DNA damage and values of serum oxidative stress markers following administration of graded doses of A. polytricha could be attributed to essential phytochemical and therapeutic constituents in A. polytricha like polyphenol and flavonoid which can be found useful in prevention and treatment of diabetes induced testicular dysfunction. In summary, AP can contribute to a reversal in DNA damage and levels of serum oxidative stress markers in treating diabetes-induced testicular dysfunction.

Influence of N-acetylcysteine on pituitary-gonadal axis hormones and protamine expression level in streptozotocin-induced diabetic male rats

Objective: To study the influence of N-acetylcysteine on the pituitary-gonadal axis hormones and protamine expression level in streptozotocin-induced diabetic male rats. Methods: Forty-two adult male Wistar rats were divided into 6 groups, with 7 rats in each group. The control group left untreated; the streptozotocin group only received 50 mg/kg body weight streptozotocin intraperitoneally for 5 days to induce diabetes; the N-acetylcysteine group only received 200 mg/kg body weight N-acetylcysteine intraperitoneally, and the streptozotocin+N- acetylcysteine groups 1, 2 and 3 received 50 mg/kg streptozotocin intraperitoneally for 5 days to induce diabetes and then received 100, 200 and 400 mg/kg body weight doses of N-acetylcysteine intraperitoneally for 28 days, respectively. Enzyme-linked immunosorbent assay was used to measure the serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone, and real-time PCR was applied for measuring protamine expression level. Results: Compared to the control and N-acetylcysteine groups, a significant decrease in the body weight, testicular weight and levels of testosterone and protamine expression was observed in the streptozotocin group and the streptozotocin+N-acetylcysteine groups 1 and 2. On the contrary, the levels of LH and FSH increased significantly. In the streptozotocin+N-acetylcysteine group 3, the body weight, testicular weight and expression level of protamine were significantly higher than those of the streptozotocin group. In the streptozotocin+N-acetylcysteine groups, testosterone and LH levels were significantly higher than and lower than the streptozotocin group, respectively. In the streptozotocin+N- acetylcysteine groups 2 and 3, the level of FSH was significantly lower than that of the streptozotocin group and streptozotocin+N- acetylcysteine group 1. Furthermore, a significant increase in the expression level of protamine was observed in the streptozotocin+N- acetylcysteine groups 2 and 3 when compared to the streptozotocin group and streptozotocin+N-acetylcysteine group 1. Conclusions: N-acetylcysteine in an optimal dose of 400 mg/kg body weight has a protective influence on the pituitary-gonadal axis hormones and also on the expression level of protamine in diabetic male rats.

Hypoglycemic and hepatoprotective effect of Rhizophora mucronata and Avicennia marina against streptozotocin-induced diabetes in male rats.

Objectives:Aqueous extracts of Rhizophora mucronata and Avicennia marina leaves were investigated for their hepatoprotective potential in diabetic rats.Materials and methods:One hundred twenty male albino rats were randomly assigned to eight equal groups (n = 15). The first group (control) comprised normal healthy rats, while the second to fifth groups were intraperitoneally injected with a single dose of streptozotocin (STZ) [60 mg/kg body weight (BW)] for induction of diabetes. Group 2 was kept as positive diabetic control, while groups 3–5 were orally treated with aqueous extracts of R. mucronata (400 mg/kg BW), A. marina (400 mg/kg BW) and with a combination of ½ a dose of the two plants, respectively, for six weeks. Groups 6–8 were non-diabetic rats that orally received aqueous extracts of R. mucronata (400 mg/kg BW), A. marina (400 mg/kg BW), and a combination of ½ a dose of the two plants, respectively, for 6 weeks.Results:STZ-induced diabetic rats showed a significant reduction in serum glucose and liver enzymes, increased serum insulin, Homeostasis Model Assessment of β-cells (HOMA-β), and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Histopathological and immunohistochemical examinations of the liver revealed improved pathologic criteria in the plant extract treated diabetic rats compared with the remarkable changes which had been seen in STZ-induced diabetic rats.Conclusion:This study suggests that the aqueous extract of R. mucronata or its combination with A. marina showed potent hypoglycemic and hepatoprotective effects for liver dysfunction, as well as histopathological and immunohistochemical changes in the liver of STZ-induced diabetic rats.

The Effects of Ripe Pistachio Hulls Hydroalcoholic Extract and Aerobic Training on Learning and Memory in Streptozotocin-induced Diabetic Male Rats.

Introduction:Diabetes mellitus has harmful effects on body functions, such as learning and memory. According to the role of exercise and medicinal plants on body health, the purpose of this study was to survey the effect of combined aerobic training and the use of Ripe Pistachio Hulls (RPH) hydro-alcoholic extract on learning and memory in streptozotocin-induced diabetic male rats.Methods:In this experimental study, 42 male Wistar rats weighing 250–280 g were used in 6 groups with an equal number of 7 rats in each one. Streptozotocin (STZ) (50 mg / kg)was used to induce diabetes, and the test protocol was applied for 8 weeks. Passive avoidance memory was assessed using a step-through passive avoidance apparatus (shuttle box). SPSS software was used to analyze the data and P<0.05 was significant.Results:The results showed that step-through latency in the acquisition trial (STLa) was not significantly different among groups. Step-through latency in retrieval (STLr 24) test significantly reduced and time spent in The Dark Compartment (TDC) decreased in treated groups compared with the diabetic control groups (P<0.001). Also, there was no significant difference between the STZ and saline diabetic groups.Conclusion:The findings of this study revealed that the RPH hydro-alcoholic extract and aerobic exercise could improve passive avoidance memory in streptozotocin diabetic rats. Meanwhile, they might be an adjuvant therapy combined with other traditional medicine.

The effect of prolonged dietary sodium nitrate treatment on the hypothalamus-pituitary-gonadal axis and testicular structure and function in streptozotocin-induced diabetic male rats.

Fifty male Wistar rats were divided into 5 groups: Control (C), control + nitrate (CN), diabetes (D), diabetes + insulin (DI), and diabetes + nitrate (DN). Diabetes was induced using 45 mg kg-1 of streptozotocin intraperitoneally. Rats in the CN and DN groups were administered sodium nitrate in drinking water (100 mg L-1). NPH insulin (2-4 U d-1) was injected subcutaneously in the DI group for 2 months. Nitrate and insulin supplementation was started one month after confirmation of diabetes. Nitrate supplementation in the DN group significantly increased the body weight (p < 0.05), sperm parameters (p < 0.001), indices of spermatogenesis (p < 0.001), and testis histopathology as well as decreased the blood glucose level (p < 0.001) compared to the untreated diabetic group, although it had no significant effect on testicular parameters, LH and FSH levels. Nitrate administration in the DN group also decreased miR-34b (p < 0.001) and p53 mRNA (p < 0.001) expression, and increased serum insulin and NOx levels compared to the untreated diabetic rats. Chronic nitrate supplementation in streptozotocin-induced diabetic rats improved fertility parameters, which may be associated with increased miR-34b and decreased p53 mRNA.

Malaysian propolis and metformin mitigate subfertility in streptozotocin-induced diabetic male rats by targeting steroidogenesis, testicular lactate transport, spermatogenesis and mating behaviour.

Diabetes mellitus is one of the risk factors for male subfertility/infertility. Malaysian propolis is reported to decrease hyperglycaemia in diabetic state. The present study investigated the protective effect of Malaysian propolis on diabetes-induced subfertility/infertility. Additionally, its combined beneficial effects with metformin were investigated. Forty adult male Sprague Dawley rats were randomly assigned into five groups, namely normal control, diabetic control, diabetic+Malaysian propolis (300mg/k.g. b.w.), diabetic+metformin (300mg/kg b.w.) and diabetic+Malaysian propolis+metformin. Diabetes was induced using a single intraperitoneal injection of streptozotocin (60mg/kg b.w.) and treatment lasted for 4weeks. During the 4th week, mating behavioural experiments were performed using sexually receptive female rats. Thereafter, fertility parameters were assessed in the female rats. Malaysian propolis increased serum and intratesticular free testosterone levels, up-regulated the mRNA levels of AR and luteinizing hormone receptor, up-regulated the mRNA and protein levels of StAR, CYP11A1, CYP17A1, 3β-HSD and 17β-HSD in the testes of diabetic rats. Furthermore, Malaysian propolis up-regulated testicular MCT2, MCT4 and lactate dehydrogenase type C mRNA levels, in addition to improving sperm parameters (count, motility, viability and normal morphology) and decreasing sperm nDNA fragmentation in diabetic rats. Malaysian propolis improved mating behaviour by increasing penile guanosine monophosphate levels. Malaysian propolis also improved fertility outcome as seen with decreases in pre- and post-implantation losses, increases in gravid uterine weight, litter size per dam and foetal weight. Malaysian propolis's effects were comparable to metformin. However, their combination yielded better results relative to the monotherapeutic interventions. Malaysian propolis improves fertility potential in diabetic state by targeting steroidogenesis, testicular lactate metabolism, spermatogenesis and mating behaviour, with better effects when co-administered with metformin. Therefore, Malaysian propolis shows a promising complementary effect with metformin in mitigating Diabetes mellitus-induced subfertility/infertility.