Testes Of Diabetic Rats Research Articles

Antidiabetic and antihyperlipidemic effects of flavonoids in streptozotocin-nicotinamide induced diabetic wistar rats

Diabetes mellitus (DM) ranks as the fourth cause of death among non-communicable diseases worldwide. Mortalities due to diabetes are associated with high cost, undesirable side effects, and less effectiveness of antidiabetic agents currently in clinical use. Therefore, this study investigated the antidiabetic and antihyperlipidemic potential of two flavonoids, 5,6,7,8-tetramethoxyflavone (1) and 5,6,7,4’-tetramethoxyflavone (2) in streptozotocin-nicotinamide induced diabetic Wistar rats. Oral acute toxicity test was conducted in male Wistar rats using the up and down method by following OECD Guideline 423. The doses, 5 and 50 mg/kg b.w were used for each flavonoid. No clinical signs of toxicity were observed for compound 1 at tested doses while compound 2 resulted in itching, reduced weight, and increased levels of creatinine. The LD50 values were established to be ≥ 50 mg/kg b.w for both compounds. In the evaluation of antidiabetic and antihyperlipidemic efficacy, diabetic Wistar rats were administered with 2.5, 5.0 and 7.5 mg/kg b.w for each compound. Compound 1 lowered the level of fasting blood glucose (FBG) significantly (p < 0.05) while compound 2 lowered FBG with no significant difference (p > 0.05) compared to the negative control. Both compounds did not avert weight loss but reduced the rate of weight loss in a dose-dependent manner. The levels of HDL-C increased with no significant difference (p > 0.05), while the levels of TC, TG, and LDL-C were reduced significantly (p < 0.05) for compound 1 compared to the negative control. Compound 2 reduced the levels of LDL-C, and increased the levels of TG significantly (p < 0.05) compared to the negative control. However, compound 2 resulted in inflation of the urinary bladder, and swelling of stomach, intestines, and testes of diabetic rats. Therefore, this study identifies and recommends 5,6,7,8-tetramethoxyflavone (1) as a promising antidiabetic and antihyperlipidemic agent.

Effects of garlic (Allium sativum L) and Citrullus colocynthis (L.) Schrad individually and in combination on male reproductive damage due to diabetes: suppression of the AGEs/RAGE/Nox-4 signaling pathway

BackgroundDiabetes Mellitus is associated with disturbances in male reproductive function and fertility. Studies have shown that oxidative stress with the subsequent inflammation and apoptosis cause these complications in diabetes. Garlic (G) (Allium sativum L) and Citrullus colocynthis (L.) Schrad (C) both have antidiabetic and antioxidant properties. Recently, we demonstrated their synergistic effects in alleviating reproductive complications when administered concomitantly. However, as even medicinal plants in long term usage may lead to some unwanted side effects of their own, we examined whether with half the original doses of these two medicinal plants we could achieve the desired results.MethodsThirty-five male Wistar rats were divided into five groups (n = 7/group): Control, Diabetic, Diabetic + G (0.5 ml/100 g BW), Diabetic + C (5 mg/kg BW) and Diabetic + GC (0.5 ml/100 g BW of garlic and 5 mg/kg BW of C. colocynthis) groups. The experimental period was 30 days.ResultsOxidative stress, advanced glycation end products (AGEs), immunoexpression of caspase-3, and expression of mRNAs for receptor for advanced glycation end products (RAGE), NADPH oxidase-4 (NOX-4) and nuclear factor kappa B increased in testis of diabetic rats. Treatment with garlic and C. colocynthis alone showed some beneficial effects, but in the combination form the effectiveness was more profound.ConclusionsWe conclude that the combination therapy of diabetic rats with lower doses is still as efficient as higher doses; therefore, the way forward for reducing complications in long term consumption.

Wharton's Jelly Mesenchymal Stem Cell Conditioned Medium Ameliorates Diabetes-Induced Testicular Damage and Sperm Abnormalities by Mitigating Oxidative Stress, Apoptosis, and Inflammation.

Diabetes leads to testicular damage and infertility. Mesenchymal stem cells and their secretory trophic factors have shown potential as regenerative therapies for diabetes and its associated complications. This study examined the effects of conditioned medium derived from Wharton's jelly mesenchymal stem cells (WJMSCs-CM) on sperm parameters, reproductive hormones, biochemical parameters, and histological changes in the testes of diabetic rats. Fifty-six male Sprague-Dawley rats (250-300 g) were assigned to eight groups: control, diabetes, and six diabetic groups receiving early or late treatments with WJMSCs-CM (D-CME, D-CML), insulin (D-INSE, D-INSL), or DMEM (D-DME, D-DML). In the early treatment groups, insulin (3 U/day, subcutaneously) and WJMSCs-CM (10 mg/week, intraperitoneally) were administered immediately after diabetes induction; in the late treatment groups, these interventions began 30 days postinduction. Blood glucose and insulin levels, along with sperm parameters, were assessed. Sex hormones, testicular antioxidant enzyme activity, malondialdehyde (MDA), and glutathione (GSH) concentrations were measured using colorimetric methods. Real-time PCR detected Bax, Bcl-2, and tumor necrosis factor-alpha (TNF-α) gene expression. Our results showed that diabetes increased blood glucose levels, decreased insulin and sex hormone levels, induced testicular oxidative stress and apoptosis, and reduced sperm parameters compared to the control. WJMSCs-CM significantly ameliorated hyperglycemia, increased insulin and sex hormone levels, and improved sperm quality. In WJMSCs-CM-treated diabetic rats, MDA levels were reduced, while GSH and antioxidant enzyme activity increased. Furthermore, WJMSCs-CM decreased the testicular Bax/Bcl-2 ratio and TNF-α expression, as well as enhanced spermatogenic, Sertoli, and Leydig cells. In conclusion, WJMSC-CM administration effectively mitigated diabetes-induced testicular damage by reducing oxidative stress, inflammation, and apoptosis. Early treatment with WJMSCs-CM was more effective than late treatment for diabetes-induced reproductive dysfunction.

Royal Jelly Enhances Spermatogenesis and Reduces Apoptosis in Diabetic Rat Testes: Histological and Immunohistochemical study.

Royal Jelly Enhances Spermatogenesis and Reduces Apoptosis in Diabetic Rat Testes: Histological and Immunohistochemical study.

Protective effects of CAPE against testicular damage in streptozotocin-induced diabetic rats

Objective: The aim of this study was to investigate the protective effect of CAPE on oxidative stress and apoptosis against streptozotocin (STZ)-induced damage in rat testis after diabetes. Materials and methods: The rats were randomly divided into 4 groups: Control animals, Control animals given CAPE, STZ-induced diabetic animals, and STZ-induced diabetic rats given CAPE. Diabetes was induced by a single intraperitoneal injection of STZ (55 mg/kg). Testicular damage was examined by using hematoxylin and eosin staining and apoptosis was determined by Caspase-3. Potential disorders associated with seminiferous tubular sperm formation were evaluated using the Johnsen score and seminiferous tubule diameters were measured using the Leica Q Win Plus Image Analysis System. Results: Diabetic rats showed an increase in degenerated germ cells along with a decrease in seminiferous tubule diameter. Also, Caspase-3 positive cells were significantly increased in diabetic rats compared to control rats. On the other hand, CAPE significantly reduced the damage and germ cell apoptosis in diabetic rat testis. In testis tissues samples. CAPE treatment significantly decreased the elevated tissue malondialdehyde levels, while increasing the reduced superoxide dismutase enzyme activity. Conclusion: These results suggest that CAPE administered intraperitoneally for 20 days to diabetic rats is a potentially beneficial agent that can be used to reduce testicular damage.

Lauric acid improves hormonal profiles, antioxidant properties, sperm quality and histomorphometric changes in testis and epididymis of streptozotocin-induced diabetic infertility rats

Lauric acid, a 12‑carbon atom medium chain fatty acid (MCFA) has strong antioxidant and antidiabetic activities. However, whether lauric acid can ameliorate hyperglycaemia-induced male reproductive damage remains unclear. The study aimed to determine the optimal dose of lauric acid with glucose-lowering activity, antioxidant potential and tissue-protective effects on the testis and epididymis of streptozotocin (STZ)-induced diabetic rats. Hyperglycaemia was induced in Sprague Dawley rats by an intravenous injection of STZ at a dose of 40 mg/kg body weight (bwt). Lauric acid (25, 50 and 100 mg/kg bwt) was administered orally for eight weeks. Weekly fasting blood glucose (FBG), glucose tolerance and insulin sensitivity were examined. Hormonal profiles (insulin and testosterone), lipid peroxidation (MDA) and antioxidant enzyme (SOD and CAT) activities were measured in the serum, testis and epididymis. The reproductive analyses were evaluated based on sperm quality and histomorphometry. Lauric acid administration significantly improved FBG levels, glucose tolerance, hormones-related fertility and oxidant-antioxidant balance in the serum, testis and epididymis compared to untreated diabetic rats. Treatment with lauric acid preserved the testicular and epididymal histomorphometry, along with the significant improvements in sperm characteristics. It is shown for the first time that lauric acid treatment at 50 mg/kg bwt is the optimal dose for ameliorating hyperglycaemia-induced male reproductive complications. We conclude that lauric acid reduced hyperglycaemia by restoring insulin and glucose homeostasis, which attributes to the regeneration of tissue damage and sperm quality in STZ-induced diabetic rats. These findings support the correlation between oxidative stress and hyperglycaemia-induced male reproductive dysfunctions.

Effects of glibenclamide and troxerutin on the sperm parameters and histopathological changes of testis in streptozotocin-induced diabetic male rats: An experimental study.

Oxidative stress is a major contributor to diabetes mellitus (DM), which leads to testicular damage and infertility. The aim of this study was to investigate the effects of glibenclamide (GL) as a chemical medicine and troxerutin (TR) as an herbal agent on sperm parameters and histopathological changes of testis in diabetic male rats. Forty male Wistar rats (230-260 gr) were randomly divided into 5 groups (n = 8/each), including control, diabetic (D), GL, TR, and GL+TR. DM was induced by the administration of 60 mg/kg streptozotocin intraperitoneally. The groups were treated with 5 mg/kg/day of GL or 150 mg/kg/day of TR via oral gavage for 4 wk. In the final stage of the treatment, blood sampling was done for biochemical analysis. The rats were then sacrificed and their left testis and epididymis were dissected for sperm analysis, histopathology, and morphometric assessment. A significant decrease in the number, motility, viability, maturity, and chromatin quality of sperm was found in diabetic rats compared to control group. (p 0.001). DM also increased the malondialdehyde level and decreased the level of the serum's total antioxidant capacity compared to the control group (p 0.001). Furthermore, we observed a significant difference in seminiferous tubule diameter, germinal epithelium height, and testicular histological abnormalities in diabetic rats compared to control group (p 0.001). Administration of GL, TR, and their combination improved the above-mentioned parameters, and treatment with TR provided a higher improvement (p 0.001). According to these findings, it can be concluded that TR plays a more influential role than GL to treat diabetic-induced infertility.

Combined effect of ethanolic leaf extracts of Carica papaya and Newbouldia laevis on the histology of testes of Alloxan-induced diabetic rats

Objective: This study was carried out to investigate the combined effect of ethanolic leaf extracts of C. papaya and N. laevis on the histology of testes of alloxan-induced diabetic rats. Methodology: Forty male wistar rats weighing 150 -180 g were procured, acclimatized for two weeks, after which were divided into eight groups of five rats each, and housed in cages. The groups were designated as groups A - H. Group A served as the control group, and received distilled water only. Animals in groups B – H were induced with diabetes using alloxan. Diabetic group B received no treatment throughout the experiment, while the diabetic groups C - H received 400 mg/kg of C. papaya leaf extract, 600 mg/kg of C. papaya leaf extract, 400 mg/kg of N. laevis leaf extract, 600 mg/kg of N. laevis leaf extract, 200 mg/kg of C. papaya + 200 mg/kg of N. laevis , 300 mg/kg of C. papaya + 300 mg/kg of N. laevis leaf extract respectively for 21 days via oral route with the aid of oral gastric tube. On the 22nd day, the animals were sacrificed via chloroform inhalation, and testes were harvested for histological studies. Result: Histopathological findings showed moderate spermatogenic arrest with interstitial hemorrhage (H) within the basal layer; mild regeneration with moderate spermatogenic arrest (SA), moderate vacoulation (V) of the sertoli cells and interstitial hemorrhage (IH); moderate regeneration with mild spermatogenic arrest (SA), mild vacoulation (V) of the sertoli cells and moderate interstitial hemorrhage (IH); moderate regeneration with active seminiferous tubules, and well enhanced spermatogenesis though there were mild pyknotic (P) appearance of the sertolli cells in some areas and interstitial hemorrhage; mild regeneration with moderate atrophy (A) of the seminiferous tubules, mild arrest of the spermatogenesis (SA) and interstitial hemorrhage (IH); moderate healing with disorganization of the seminiferous tubules and interstitial fibrosis (IF); and moderate healing with distortion (D) of the seminiferous tubules, interstitial fibrosis (IF) and mild arrest of the spermatogenesis (AS) on the histology of testes in groups B - H that received variable doses of C. papaya and N. laevis leaf extracts respectively. Conclusion: Combined leaf extracts of Carica papaya and Newbouldia laevis leaf extracts have antidiabetic and ameliorating effects on the histology of testes of alloxan induced wistar rats.

Combined effect of ethanolic leaf extracts of Carica papaya and Newbouldia laevis on the histology of testes of Alloxan-induced diabetic rats

Combined effect of ethanolic leaf extracts of Carica papaya and Newbouldia laevis on the histology of testes of Alloxan-induced diabetic rats

Effects of electroacupuncture at ST36 and BL20 on the diabetic rat testis.

We aimed to evaluate the effects of electroacupuncture (EA) at ST36 and BL20 on the testicular tissues in a rat model of diabetes and to explore the mechanisms of action. A total of 34 male Sprague-Dawley rats were allocated to a control group (n = 10), diabetes (D) group (n = 12) or diabetes + acupuncture (DA) group (n = 12). To model diabetes, rats in groups D and DA received an intraperitoneal injection of a single dose of 35 mg/kg streptozotocin (STZ) dissolved in citrate buffer (pH = 4.5; 0.1 M) after 2 weeks of high-fat diet administration. Under xylazine/ketamine anesthesia, stainless steel needles (30 mm × 0.25 mm) were inserted bilaterally at ST36 and BL20. The needles were connected to an EA device via cables, and EA was applied for 30 min (15 Hz frequency and 0.2-1 mA intensity) twice a week for 5 weeks. The effects of EA at ST36 and BL20 on blood glucose levels and body weight, biochemical parameters, histopathological, morphometric and immunohistochemical findings, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis were evaluated. A significant decrease was detected in DA versus D groups in blood glucose levels, basement membrane thickness and apoptotic cell/tubule indices. In addition, there was a significant increase in the Johnsen scores, seminiferous tubule diameters, serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone, proliferation indices, and sex hormone-binding globulin (SHBG) and insulin-like peptide 3 (INSL3) immunoreactivities. EA had multiple positive effects on blood glucose homeostasis and testicular structure/function in this rat model of diabetes. EA may be effective at preventing or eliminating histopathological damage in the diabetic testis.

Dietary zinc deficient condition increases the Bisphenol A toxicity in diabetic rat testes.

Bisphenol A (BPA) is a widely used endocrine disrupter that causes male reproductive dysfunction in humans and rodents. Diabetes-induced hyperglycemia alters spermatogenesis and antioxidant status, which negatively impacts male fertility in adults. Zinc (Zn) deficiency is a global health concern maintaining the testicular structure and functions in developing gonads. The present experiment was designed to investigate the role of Zn deficiency on BPA-induced germ cell and male gonadal toxicity in diabetic conditions. Rats were randomly divided into eight different groups - control (normal feed and water), BPA (10mg/kg/day), ZDD (fed with a Zn-deficient diet), DIA (diabetic), BPA+ZDD, BPA+DIA, ZDD+DIA and BPA+ZDD+DIA for four weeks. Animals' body and organ weight, sperm count, motility and sperm morphology were examined; testes and epididymis histopathology were investigated. Testicular DNA damage and sperm apoptosis were evaluated by halo and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays respectively. Testicular catalase and octamer-binding transcription factor 4 (OCT4) expressions were evaluated by western blot analysis. The present results demonstrated that dietary Zn-deficient condition significantly increased the BPA-induced testicular, epididymal and sperm toxicity in diabetic rats due to hypogonadism, increased sperm abnormalities, epididymis, testicular structure and DNA damages, sperm apoptosis as well as decreased testicular catalase and OCT4 expressions. The present results revealed that dietary Zn-deficient condition exacerbated the BPA-induced testicular and epididymal toxicity as well as perturbed the general male reproductive health in diabetic rats.

Role of aquaporin 9 in hyperglycaemia-induced testicular leydig cell apoptosis

Hyperglycaemia is an early symptom of diabetes mellitus (DM) and hyperglycaemia-induced apoptosis is the most widely accepted cause for diabetes induced male infertility/subfertility. Aquaporin (AQP) isoforms (AQP0-12), are water channels involved in maintaining water homeostasis and regulate fluid absorption and/or excretion; thus, play a key role in reproductive function. Further, AQPs regulate diabetic complications, apoptosis induced by hyperglycaemia/high glucose (HG) and also involved in insulin regulation. Herein, we investigated AQP 9 role in hyperglycaemia-induced testicular Leydig cell apoptosis. In-vivo and in-vitro role of AQP 9 on hyperglycaemia induced Leydig cell apoptosis was analysed in diabetic rat testis and LC-540 rat Leydig cells by Real Time-PCR, western blotting and siRNA knock-down experiments. In addition, HG effect on viability and morphological changes due to apoptosis in cells were assessed by MTT and fluorescence microscopy. In-vivo and in-vitro AQP 9 expressions were increased in diabetic testicular Leydig cells. Hyperglycaemia caused apoptosis in testicular Leydig cells by increasing Cytochrome c, Bax and decreasing Bcl-2. Furthermore, AQP 9 knock-down resulted in downregulation of pro-apoptotic proteins and in contrast, upregulated anti-apoptotic protein expressions; thereby decreased apoptosis in testicular Leydig cells under hyperglycemia. Our findings collectively suggest, AQP 9 role in hyperglycaemia-induced apoptosis in testicular Leydig cells.

Aquaporin 9 regulates Leydig cell steroidogenesis in diabetes

Diabetes mellitus induced hyperglycemia increases oxidative stress, which contributes to impairment of male reproductive function. Aquaporins (AQPs) belong to a transmembrane protein superfamily containing 13 isoforms (AQP0-12), differentially expressed in various organs, and play a pivotal role in male reproductive function. In the current study, we investigated the relationship between AQPs and testicular steroidogenesis under hyperglycemia in vivo and in vitro. The effect of high glucose on the role of AQPs in Leydig cell steroidogenesis was analyzed in diabetic rats (in-vivo) and LC540 rat Leydig cells (in vitro) via enzyme assays, quantitative RT-PCR, siRNA knock down and western blotting. AQP 9 was significantly up-regulated in STZ-induced diabetic rat testis and high glucose treated LC540 cells. Further, oxidative stress marker nuclear factor erythroid 2-related factor 2 (Nrf2) expression was decreased with impaired testicular steroidogenesis under hyperglycemia. Knock-down of AQP 9 resulted in increased Nrf2 expression and thus increased testicular steroidogenesis in hyperglycemia. Diabetes-associated hyperglycemia induced oxidative stress is a widely proven cause for diabetes-related male infertility. Our results collectively suggest that AQP 9 impairs testicular steroidogenesis via the regulation of oxidative stress in diabetes.

Protective properties of Rydingia persica in reproductive complications induced by diabetes in male rats: An experimental study.

Background In Iranian traditional medicine, Rydingia persica (R.P) is commonly used to treat diabetes mellitus (DM).ObjectiveWe assessed the protective effects of R.P against testis and epididymis oxidative stress and the hormonal changes induced by DM.Materials and MethodsForty male Wistar rats (12 wk old) weighing 230-270 gr were divided into five groups (n = 8/each): 1. Control (C); 2. diabetic (D); 3. diabetic + R.P200 (D+R200); 4. diabetic + R.P400 (D+R400); and 5. diabetic + R.P600 (D+R600). Groups C and D received 2 ml of normal saline orally daily for two wk and groups D+R200, D+R400, and D+R600 received 200, 400, and 600 mg/kg body weight of R.P powder, respectively, orally daily for two wk. DM was induced by a single intraperitoneal injection of streptozotocin at 60 mg/kg body weight. We assessed malondialdehyde, glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase, hydrogen peroxide, and glutathione in both the testis and epididymis and also the histological changes of the testis.ResultsDiabetic rats showed a significantly increased and decreased level of oxidant and antioxidant factors, respectively, and a significantly lower level of serum testosterone and luteinizing hormone than the control group. In the histological study of the testis, deteriorations were observed. Treatment with R.P reversed these changes toward the state of the control group with the highest effectiveness shown by group D+R600.ConclusionThe data obtained suggest that R.P powder has antioxidant effects on testis and epididymis tissues in diabetic rats and that it improves histological testicular structure in diabetics. It can also correct testosterone and luteinizing hormone changes induced by DM

The Effect of Chlorogenic Acid on Endoplasmic Reticulum Stress and Steroidogenesis in the Testes of Diabetic Rats: Study of mRNA Expressions of GRP78, XBP1s, 3β-HSD, and 17β-HSD

Diabetes mellitus (DM) is a chronic endocrine metabolic disorder that can increase the incidence of infertility. Excessive production of reactive oxygen species (ROS) can trigger oxidative stress reactions and reduce antioxidant content. The increase of ROS can exert an impact on the endoplasmic reticulum (ER) stress conditions and inhibit the steroidogenesis of the testes. The objectives of the current study were to determine the effect of chlorogenic acid (CGA) as an antioxidant in reducing ER stress conditions (mRNA expressions of GRP78, XBP1s), and to increase steroidogenesis (mRNA expressions of 3β-HSD and 17β-HSD) in the testis of DM rats. A total of 24 rats were randomly divided into six groups, namely: control group, DM1.5 months, DM2 months, and DM group were treated with CGA with three different doses (12.5 mg/kgBW, 25 mg/kgBW, and 50 mg/kgBW), respectively. Testicular tissue was isolated for examination of GRP78, XBP1s, 3β-HSD, and 17β-HSD mRNA expressions using RT-PCR. In the CGA1 group, GRP78 mRNA expression level was lower than in the DM2 group and was statistically different (p=0.021). XBP1s mRNA expression in the CGA1 group was lower and significantly different when compared to the DM2 group (p=0.018). The mRNA expression of 3β -HSD in the CGA1 group was higher than that in the DM1.5 and DM2 groups, which were statistically significant with p=0.000 and p=0,008. The comparison of 17β - HSD mRNA expression in the CGA1 group was higher than the DM1,5 and DM2 groups with p=0.013 and p=0.012. Administration of CGA at a dose of 12.5 mg/kgBW can reduce ER stress conditions and increase testicular steroidogenesis in DM rat models. These results were seen based on low GRP78 and XBP1s mRNA expressions, and high 3β-HSD and 17β-HSD mRNA expressions after CGA administration.

Role of JNK, TGF-β1, Akt, IL-1β and INSL-3 in proanthocyanidin protection against apoptosis in diabetic rat testis

ABSTRACT We investigated how proanthocyanidin treatment altered c-Jun N-terminal kinases, transforming growth factor beta 1, serine/threonine-specific protein kinase, interleukin 1 beta and insulin-like 3 expression in the testis of diabetic rats. We used 24 Wistar albino male rats divided into four groups. Group 1 was untreated control. Group 2 was treated with 40 mg/kg streptozotocin (STZ) for 5 days. Group 3 was treated with 40 mg/kg STZ + 250 mg/kg proanthocyanidin once daily for six weeks. Group 4 was treated with 40 mg/kg STZ + 250 mg/kg proanthocyanidin. Superoxide dismutase activity was reduced in groups 3 and 4 compared to group 2. Glutathione peroxidase activity was increased significantly in groups 3 and 4 compared to groups 1 and 2. Catalase activity was decreased in group 4 compared to group 2. We found that proanthocyanidin increased cell proliferation in diabetic testis. Phospho-JNK and TGF-β1 immunostaining was decreased groups 3 and 4 compared to group 2, while p-Akt immunostaining was increased in groups 3 and 4. The number of IL-1β immunostained cells in groups 3 and 4 was decreased compared to group 2. INSL-3 immunostaining was increased significantly in group 3 compared to group 2. Our findings indicate that proanthocyanidin ameliorated diabetes related testicular dysfunction. Proanthocyanidin contributes to a balanced oxidant-antioxidant status, and balanced proliferation and apoptosis activity in the germinal cells.

Oxidative Stress Status in Testis of Type-2 Diabetic Rats Treated with Delta-9-Tetrahydrocannabinol

Objective: Type-2 diabetes (T2D) is a multifactorial disease that occurs as a result of impaired insulin secretion and increased glucose. Researchers emphasize that oxidative stress prevention and improvement strategies are important in the general treatment of T2D. It is reported that delta-9-tetrahydrocannabinol (THC), a component of the cannabis plant, has positive effects against oxidative stress and inflammation. Therefore, this study explored the inhibitory effects of THC on oxidative damage of testis in type-2 diabetic rats. Materials and Methods: Adult Spraque-Dawley rats were separated into 4 groups. In the control group, physiological saline was given intraperitoneally. In the T2D model group (T2DM), streptozotocin (STZ) + nicotinamide (NAD) was administered intraperitoneally. Three mg/kg/day THC was given to the THC and T2DM+THC groups for 7 days, intraperitoneally. Glutathione (GSH), malondialdehyde (MDA), and protein carbonyl levels (PCO), and superoxide dismutase (SOD) activity were measured spectrophotometrically in testicular tissue. Total oxidant and antioxidant status were determined by ELISA. Results: Testicular GSH level and SOD activity were significantly decreased in T2D, while MDA and PCO levels increased. In contrast to this effect, the THC treatment increased GSH levels and SOD activity in diabetics, but decreased MDA and PCO levels. Conclusion: According to the study results, THC may have an oxidative stress inhibitory effect on diabetic rat testis.

Ameliorative effect of hesperidin on streptozotocin‐diabetes mellitus‐induced testicular DNA damage and sperm quality degradation in Sprague–Dawley rats

This study aimed to investigate the effect of hesperidin on reproductive damage caused by diabetes mellitus. A total of 24 adult male rats were divided into four groups: control group, hesperidin group, diabetes mellitus group, and diabetes mellitus+hesperidin group. The study was conducted for 4weeks. At the end of the study, the rats were sacrificed and testicular oxidative stress markers (MDA, GSH, GSH-Px, SOD, and CAT), DNA damage in testes (8-OHdG), and routine sperm parameters were evaluated. According to the results of the study, most of the parameters were similar in the control and hesperidin groups but CAT activity in the hesperidin group was statistically higher than the control group. Also, diabetes mellitus (DM) significantly increased MDA levels and decreased enzymatic antioxidant (GSH-Px, SOD, CAT) activities and nonenzymatic (GSH) antioxidant levels. On the other hand, hesperidin supplementation significantly decreased oxidative stress and increased enzymatic antioxidant activities and nonenzymatic antioxidant levels due to the antioxidant effect. Also, DM increased DNA damage levels in testicular tissue and hesperidin supplementation significantly decreased DNA damage levels in testes of diabetic male rats. Besides, sperm motility significantly decreased while abnormal sperm rate and dead sperm rate were significantly increased in diabetic rats. Hesperidin supplementation significantly reduced these side effects in diabetic rats. In conclusion, hesperidin supplementation could be beneficial for decreasing the side effects on the male reproductive system caused by DM in rats. PRACTICAL APPLICATIONS: Diabetes is an important metabolic disease, affecting quality of life and fertility. Hesperidin has an antioxidant effect and has a potential protective effect on reproductive toxicity in diabetic male rats. Hesperidin decreased oxidative stress, and DNA damage in testis resulted from hyperglycemia and improved sperm quality in diabetic rats. The hesperidin supplementation could be a good strategy to protect male fertility in diabetic patients.

MicroRNA regulation of the proliferation and apoptosis of Leydig cells in diabetes

BackgroundThe number of patients with diabetes is increasing worldwide. Diabetic testicular damage can cause spermiogenesis disorders and sexual dysfunction. We thus explored the role of miRNAs in diabetic testicular damage, and revealed that they could serve as effective prevention and treatment therapeutic targets.MethodsStreptozotocin (STZ) was used to generate a rat model of type 2 diabetes. Rat testicular tissues were used for miRNA and mRNA sequencing. Through bioinformatics analysis, we constructed an miRNA–mRNA diabetic testicular damage regulatory network and screened for key miRNAs. We also used Leydig cells to generate a diabetic cell model and detected the downstream target genes of miRNAs, secretion of testosterone, and proliferation and apoptotic levels to elucidate the role and mechanism of the selected miRNAs in diabetic testicular damage.ResultsUsing second-generation sequencing, we identified 19 differentially expressed miRNAs and 555 mRNAs in the testes of diabetic rats. Based on computational prediction of targets and negative regulation relationships, we constructed a miRNA–mRNA regulatory network, including 12 miRNAs and 215 mRNAs. KEGG enrichment analysis revealed that genes were more concentrated on the survival signalling pathway. Based on this, we screened 2 key miRNAs, miR-504 and miR-935. In vitro, glucose could induce an increase in miR-504 and miR-935, whereas a decrease in MEK5 and MEF2C in a dose-dependent manner. Overexpression of miR-504 and miR-935 led to the decreased expression of MEK5 and MEF2C, decreased proliferation rate of Leydig cells, increased apoptotic rate, and decreased secretion of testosterone. Whereas, knockdown of miR-504 and miR-935 displayed opposite tendencies.ConclusionsmiRNAs play important roles in diabetic testicular damage. miR-504 and miR-935 might regulate testicular damage through the classic survival pathway of MEK5-ERK5-MEF2C. Targeted inhibition of miR-504 and miR-935 could reverse the high-glucose-induced testicular complications, thus posing as a potential therapeutic approach in diabetic testicular injury.

Antiapoptotic and antioxidative effects of cerium oxide nanoparticles on the testicular tissues of streptozotocin-induced diabetic rats: An experimental study.

BackgroundCerium dioxide nanoparticles (CNPs) due to the antidiabetic and antioxidant activities are proposed for the treatment of oxidative stress-associated diseases.ObjectiveTo examine the impact of CNPs on hyperglycemia-induced apoptosis and oxidative stress in the testis of diabetic rats.Materials and MethodsTwenty-four male rats were divided into four groups (n = 6/each) as diabetic rats, CNPs group, diabetic + CNPs rats, and controls. The control group was fed only mouse food and water. Rats became diabetic through receiving streptozotocin (STZ) 60 mg/kg. CNPs were given to the rats at a dose of 30 mg/kg daily for 2 wk. Malondialdehyde and total thiol group (TTG) levels were measured using spectrofluorometer. Expression of b-cell lymphoma protein 2-associated X protein (BAX) and b-cell lymphoma protein 2 (Bcl-2) were investigated using quantitative real-time polymerase chain reaction. Western blot analysis was used to examine caspase 3 protein levels.ResultsThe content of malondialdehyde significantly increased in the STZ-diabetic rats, while TTG levels demonstrated a remarkable decrease. Caspase-3, BAX, and BAX/Bcl-2 mRNA ratio raised significantly in the STZ-diabetic rats. On the other hand, Bcl-2 mRNA levels reduced in the testis of diabetic rats (p = 0.006). Intervention with CNPs caused a substantial increase in the TTG levels, while the malondialdehyde contents, caspase-3, BAX levels, as well as BAX/Bcl-2 mRNA ratio were considerably decreased following CNPs treatment. Administration of CNPs increased mRNA levels of Bcl-2 (p 0.0001).ConclusionCNPs treatment attenuates testicular apoptosis and oxidative stress induced by diabetes. This nanoparticle might be suggested for the treatment of diabetes-associated reproductive disorders.