Erythritol attenuates testicular dysfunction in diabetic rat via suppression of oxidative stress, inflammation and apoptosis.

Hyperglycemia -induced oxidative stress and inflammation have been closely associated with diabetes complications including testicular dysfunction. Conversely, reducing blood glucose and/or use of antioxidant have been associated with reduced diabetes complications. The present study investigated the effect of erythritol (which has both antioxidant and blood glucose lowering function) on diabetes -induced testicular dysfunction in rats. Thirty male Wistar rats (170-200g) were randomly divided into 5 groups: 1) control; 2) erythritol; 3) diabetic; 4) diabetic + erythritol 1000 mg/kg; and 5) diabetic + metformin 300 mg/kg. After 8 weeks of treatment period, blood sample, testes and epididymis were collected for reproductive hormones, biochemical and histological examinations, and sperm analysis respectively. There was a significant (p < 0.05) decrease in sperm count, sperm motility, sperm morphology and serum reproductive hormones (Follicle stimulating hormone (FSH), Leutinizing hormone (LH), testosterone and gonadotropin releasing hormone (GnRH)) of diabetes rat compared to control. Also, diabetes rat showed increase in sperm and testicular malonaldehyde (MDA) and decrease in sperm and testicular superoxide dismutase (SOD) activity and glutathione (GSH) level. Further, diabetes rat showed reduced testicular weight, decreased testicular 17ß-HSD and 3ß-HSD activity and testicular histo-architectural alteration which were accompanied by decrease testicular vascular endothelial growth factor (VEGF) and concomitant increase in testicular myeloperoxidase activity and level of caspase 3. The present results indicates that induction of diabetes in rat causes reduction in the level of reproductive hormones (Testosterone, LH and FSH) as well as sperm and testicular oxidative stress causing abnormal sperm parameters, and biochemical and histo-architectural alterations in the testes of rats. In addition, the present results suggest that erythritol administration reduced blood glucose and ameliorated hyperglycemia -induced oxidative stress -mediated alterations in both sperm and testes of diabetes rat. Further, the present study suggests that erythritol improved testicular oxidative stress, inflammation and apoptosis by up-regulating VEGF.

Blood glucose lowering and anti-oxidant potential of erythritol: An in vitro and in vivo study.

Background: Diabetes is a major cause of death worldwide and Nigeria is not an exception. The quest to lower sugar levels has become a major factor in the management of diabetes; this has occasioned the use of substitutes for refined sugar in beverages. Erythritol is a natural sweetener gaining immense interest in recent times. Like metformin, erythritol has shown hydroxyl radical scavenging ability and has metabolic profile suitable for diabetics. Therefore, the blood glucose-lowering and anti-oxidant properties of erythritol under in vitro and in vivo systems were accessed. Methods: Radical scavenging assay (ABTS and DPPH) and inhibition of carbohydrate digestive enzymes (alpha-amylase and alpha-glucosidase) were employed to determine in vitro anti-oxidant and glucose regulatory function of erythritol respectively. Molecular docking studies were performed between 3D structures of human pancreatic alpha-amylase and alpha-glucosidase, isomaltase from saccharomyces cerevisiae with erythritol. The drug-like activity of erythritol was also assessed.Thereafter, we investigated the effect of erythritol on blood glucose and antioxidant status of normal and streptozocin- nicotinamide-induced diabetes rats which were grouped into five (n = 5); Normal, Ery (normal and administered erythritol), Db (diabetic control), Db + Ery (diabetic and administered erythritol), and Db + Met (diabetic and administered metformin). Results: Erythritol showed a considerable radical scavenging activity and an ability to inhibit alpha-amylase and alpha-glucosidase in vitro. Also, a significant reduction in glucose intolerance, blood glucose and hemoglobin A1c levels and improved antioxidant level was seen in erythritol-treated diabetic rats. Conclusion: Erythritol showed anti-oxidant activity, alpha amylase and glucosidase enzyme inhibition property, improved antioxidant status and ameliorated blood glucose, HbA1c, and glucose intolerance following diabetes.

Impact of hypoxia on male reproductive functions.

Male reproductive functions, which include testicular steroidogenesis, spermatogenesis, and sexual/erectile functions are key in male fertility, but may be adversely altered by several factors, including hypoxia. This review demonstrates the impact of hypoxia on male reproductive functions. Acute exposure to hypoxia promotes testosterone production via stimulation of autophagy and upregulation of steroidogenic enzymes and voltage-gated L-type calcium channel, nonetheless, chronic exposure to hypoxia impairs steroidogenesis via suppression of the hypothalamic-pituitary-testicular axis. Also, hypoxia distorts spermatogenesis and reduces sperm count, motility, and normal forms via upregulation of VEGF and oxidative stress-sensitive signaling. Furthermore, hypoxia induces sexual and erectile dysfunction via a testosterone-dependent downregulation of NO/cGMP signaling and upregulation of PGE1/TGFß1-driven penile endothelial dysfunction. Notably, hypoxia programs male sexual function and spermatogenesis/sperm quality via feminization and demasculinization of males and oxidative stress-mediated alteration in sperm DNA methylation. Since oxidative stress plays a central role in hypoxia-induced male reproductive dysfunction, studies exploring the effects of antioxidants and upregulation of transcription of antioxidants on hypoxia-induced male reproductive dysfunction are recommended.

Anti-atherogenic and cardio-protective properties of sweet melon (Cucumis melo. L. Inodorus) seed extract on high fat diet induced obesity in male wistar rats.

BACKGROUND: Cucumis melon is a medicinal plant with multiple pharmacological properties such as anti-inflammatory, antioxidant, and diuretic effects. An increasing body of scientific evidence established the anti-diabetic/anti-obesity effects of Cucumis melo in humans, mice, and hamster models. However, there are no tangible reports on its ability to prevent cardiovascular complications following diet-induced obesity. The anti-atherogenic and cardioprotective effects of the Methanolic extract of Cucumis melo. L. Inodorus seeds on a high-fat diet (HFD)-induced obese rats was assessed in this study.  METHODS: Forty male Wistar rats were randomly divided into five groups, (n = 8/group); i.e., Normal (N), HFD, HFD + 50 mg/kg b.w. of MCMs (Methanolic extract of Cucumis melon seeds), HFD + 100 mg/Kg b.w. of MCMs and HFD + 200 mg/kg b.w. of MCMs. The experimental animals were anaesthetized and sacrificed after 10 weeks, and blood samples and heart tissue were collected for further analysis. Using the Graph Pad Prism version 5.0, the results expressed as Mean ± SD was tested using the one-way ANOVA to show intergroup differences, followed by Bonferonni 's post hoc test. The level of significance was determined at P ≤ 0.05. RESULTS: MCMs significantly (P < 0.05) reduced body weight, adiposity index, total fat mass, low-density lipoprotein cholesterol (LDL-c), and total cholesterol (TC) compared with the HFD obese groups MCMs caused a significant reduction in the body weight, total fat mass, adiposity index, low-density lipoprotein cholesterol (LDL-c), and total cholesterol (TC) when compared to the animals in HFD obese groups. Also, the Atherogenic index of plasma (AIP), Castelli index and, malondialdehyde (MDA) significantly (P < 0.05) decreased in MCMs treated groups compared to the HFD obese group. The catalase, protein, and HDL levels were significantly increased in MCMs treated groups compared to HFD-obese animals. Expression of nitric oxide in the form of nitrite in the heart tissue significantly increased in the MCMs treated compared to the HFD-obese rats, with the majority of the positive results recorded at 100 mg/Kg b.w. of MCMs. CONCLUSIONS: MCMs have anti-atherogenic and Cardio-protective properties on High Fat Diet-Induced Obesity in Male rats via an antioxidant and nitric oxide-dependent mechanism. Further study is recommended to evaluate the molecular mechanisms to which these anti-atherogenic and cardio-protective actions can be attributed and exploit the GCMS result in the development of drug candidates.

Suppression of glutathione system and upregulation of caspase 3-dependent apoptosis mediate rohypnol-induced gastric injury.

Objectives: This study investigated the impact of rohypnol on gastric tissue integrity.Methods: Forty male Wistar rats were randomized into control, low dose rohypnol-treated, high dose rohypnol-treated, low dose rohypnol-treated recovery and high dose rohypnol-treated recovery groups.Results: Rohypnol caused significant rise in gastric malondialdehyde (MDA), oxidized glutathione (GSSG), nitric oxide (NO), tumour necrotic factor-α (TNF-α), and interleukin-6 (IL-6) levels. Also, rohypnol caused reductions in gastric reduced glutathione (GSH) (as well as GSH/GSSG), and activities of superoxide dismutase (SOD), catalase, glutathione-S-transferase (GST), glutathione peroxidase (GPx), cyclo-oxygenase (COX-2). Furthermore, rohypnol upregulated caspase 3 activity and induced gastric DNA damage, evident by a rise in 8-hydroxydeoxyguanosine (8-OHdG) and DNA fragmentation index (DFI) in gastric tissue. These alterations were coupled with reduced gastric weight and distorted gastric cytoarchitecture. Cessation of rohypnol caused a significant but not complete reversal of rohypnol-induced gastric damage.Conclusion: This study revealed that rohypnol induced gastric injury by suppressing glutathione content and COX-2 activity, and upregulating caspase 3-dependent apoptosis, which was partly reversed by rohypnol withdrawal.

Glutamine restores testicular glutathione-dependent antioxidant defense and upregulates NO/cGMP signaling in sleep deprivation-induced reproductive dysfunction in rats.

Oxidative stress has been linked with sleep deprivation (SD)-induced pathological conditions and reproductive dysfunction. On the other hand, glutamine has been established to have antioxidant property. However, the impact of SD, with or without glutamine, on male reproductive function is yet to be elucidated. Thus, this study was designed to investigate the role of SD, with or without glutamine, on male reproductive function and possible associated mechanisms. Ten-week old male Wistar rats weighing 175.6 g± 0.42 were randomly assigned into vehicle that received per os (p.o.) distilled water, glutamine (1 g/kg; po), SD, and SD + glutamine that received treatments as glutamine and SD. Treatment/exposure lasted for 72 h. The results showed that SD led to reduced body weight, seminiferous luminal and epididymal sperm density, low sperm quality, increased testicular and epididymal malondialdehyde, uric acid, DNA fragmentation, and testicular injury markers. In addition, SD caused a reduction in reduced glutathione level and activities of superoxide dismutase, catalase, glucose-6-phosphate dehydrogenase, glutathione peroxidase, and glutathione-S-transferase. Also, SD increased tumor necrotic factor-α, interleukin-1ß, and nuclear factor-kappa B levels. Furthermore SD led to impaired libido and erectile dysfunction, and suppression of circulatory nitric oxide, gonadotropins and testosterone, and penile cGMP. However, glutamine attenuated the effects induced by SD. Taken together, the findings of this study demonstrate that SD induces reproductive dysfunction via glutathione-dependent defense depletion and down-regulation of NO/cGMP signaling, which was abolished by glutamine supplementation.

Upregulation of Uric Acid Production and Caspase 3 Signalling Mediates Rohypnol-Induced Cardiorenal Damage.

The global prevalence of illicit drug use is on the increase with attendant complications like cardiorenal collapse. One such substance of abuse is rohypnol. Despite its ban in most countries, it remains a popular substance of abuse. Whether or not rohypnol induces cardiorenal injury and the associated mechanism is yet to be elucidated. Therefore, the present study investigated the effect of rohypnol on cardiorenal integrity and functions, and glucolipid metabolism. Forty-eight male Wistar rats randomized into six groups (n = 8/group) received (per os) vehicle, low-dose (2 mg/kg) and high-dose (4 mg/kg) rohypnol once daily for twenty eight days, with or without a cessation period. Data revealed that rohypnol exposure irreversibly caused insulin resistance, hyperglycaemia, and dyslipidaemia. This was accompanied by reduced cardiorenal mass and impaired cardiorenal cytoarchitecture and function. Furthermore, rohypnol treatment promoted oxidative stress, inflammation, genotoxicity, and decreased cardiorenal activities of Na+-K+-ATPase, Ca2+-ATPase, and Mg2+-ATPase. These alterations were associated with enhanced uric acid generation and caspase 3 activity in the cardiorenal complex. Thus, this study reveals that rohypnol exposure triggers cardiorenal toxicity with incident insulin resistance, glucolipid and cardiorenal proton pump dysregulation, altered redox state, and inflammation via enhancement of uric acid generation and caspase 3-dependent mechanism.

Codeine alters female reproductive function by targeting ovarian steroidogenesis and folliculogenesis via the induction of oxidative stress, inflammation, and apoptosis.

The rise in the abuse of codeine raises concerns about its impact on the health of users, and little has appeared on its effect on the female reproductive function. Therefore, this study evaluated the impact of codeine on female reproductive function. We administered codeine at low (2 mg/kg) and high (5 mg/kg) doses to female animals prior to mating for 8 weeks. In comparison with a vehicle-treated group, we then assessed the impact of codeine on body weight gain and ovarian weight, female sexual behaviour, ovarian steroidogenesis, and folliculogenesis. The role of oxidative stress, inflammation, and apoptosis were also evaluated. Codeine at either dose elicited a profound deficit in the absolute and relative ovarian weight, indicative of ovarian toxicity. Also, codeine induced female sexual dysfunction, and suppressed ovarian steroidogenesis and folliculogenesis, with degeneration of the ovarian cytoarchitecture and follicles. The effects of codeine were associated with a rise in ovarian hydroxyl radical generation and oxidative stress, evident by an increase in ovarian malondialdehyde, a reduction in reduced glutathione, and a decline in the activities of ovarian enzymatic antioxidants. In addition, codeine triggered an increase in the ovarian concentration of inflammatory cytokines, TNF-α and IL-1ß, and myeloperoxidase activity. Furthermore, codeine caused an increase in 8-hydroxydeoxyguanosine (8OHdG), ovarian DNA fragmentation, and caspase-3 activity, suggestive of genotoxicity and apoptosis respectively. The current study provides some of the first evidence for the adverse effects of prolong codeine use on female sexual function, ovarian steroidogenesis, and folliculogenesis. It also emphasizes the reproductive health consequences of drug abuse.

Omega-3 fatty acid rescues ischaemia/perfusion-induced testicular and sperm damage via modulation of lactate transport and xanthine oxidase/uric acid signaling.

This study aimed to explore the potential antioxidant, anti-inflammatory, and anti-apoptotic effects of omega 3 fatty acid (Ω-3) in a rat model of testicular torsion/detorsion (T/D). Under ketamine/xylazine anaesthesia, age-matched adult male Wistar rats of comparable weight underwent sham-operation or testicular torsion by fixing the left testis rotated at 720° for two and half hours. After detorsion, animals were treated with either olive oil as vehicle or Ω-3 subcutaneously for three days. On post-operative day 3, rats were culled and the ipsilateral and contralateral testes, as well as obtained blood samples, were analyzed. Our findings revealed that T/D led to significant poor weight gain, distorted gross anatomy, and cytoarchitecture of the testes, low sperm quality, redox imbalance, and inflammation of the ipsilateral and contralateral testes. This was accompanied by reduced circulatory testosterone, a decline in testicular lactate metabolism and transport, upregulation of xanthine oxidase/uric acid signaling, and increased testicular DNA fragmentation. Administration of Ω-3 attenuated T/D-induced damage to the testes and sperm cells with a significant rise in the level of serum testosterone. Enhancement of lactate transport and down-regulation of xanthine oxidase/uric acid signaling by Ω-3 may be beneficial in protecting against T/D-related oxido-inflammatory damage and male infertility.

Apoptotic inducement of neuronal cells by codeine: possible role of disrupted redox state and caspase 3 signaling.

BACKGROUND: Codeine, a common drug of abuse, has been reported to induce organ damage; however, there are scanty available data on the effects of codeine on the brain. OBJECTIVE: Thus, we tested the hypothesis that redox dysregulation and inflammation of the brain induced by codeine exposure is 8-OHdG and/or caspase 3-dependent. METHODS: New Zealand White rabbits (Oryctolagus cuniculus) received vehicle (control; n = 7), low-dose codeine (4 mg/kg/day p.o; n = 6), or high-dose codeine (10 mg/kg/day p.o; n = 6) for six weeks. Body weight was checked before and after the study. RESULTS: Findings showed that codeine exposure resulted in redox dysregulation (evident by elevated MDA and H2O2 accompanied by reduced enzymatic antioxidant activities), elevated MPO activity, and distorted cytoarchitecture of the brain tissue. The observed codeine-induced redox imbalance and brain inflammation was accompanied by depletion of neuronal and purkinje cells, reduced AchE activity, and elevated 8-OHdG levels and caspase 3 activity. CONCLUSIONS: The current study demonstrates that chronic codeine use induces oxido-inflammatory response and apoptosis of the brain tissue that is associated with neuronal and purkinje cells injury, and impaired AchE activity through 8-OHdG and/or caspase 3-dependent pathway.

Codeine exerts cardiorenal injury via upregulation of adenine deaminase/xanthine oxidase and caspase 3 signaling.

AIMS: Codeine treatment has been shown to be associated with glucolipid deregulation, though data reporting this are inconsistent and the mechanisms are not well understood. Perturbation of glutathione-dependent antioxidant defense and adenosine deaminase (ADA)/xanthine oxidase (XO) signaling has been implicated in the pathogenesis of cardiometabolic disorders. We thus, hypothesized that depletion of glutathione contents and upregulation of ADA/XO are involved in codeine-induced glucolipid deregulation. The present study also investigated whether or not codeine administration would induce genotoxicity and apoptosis in cardiac and renal tissues. MATERIALS AND METHODS: Male New Zealand rabbits received per os distilled water or codeine, either in low dose (4 mg/kg) or high dose (10 mg/kg) for 6 weeks. KEY FINDINGS: Codeine treatment led to reduced absolute and relative cardiac and renal mass independent of body weight change, increased blood glucose, total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL-C), as well as increased atherogenic indices and triglyceride-glucose index (TyG). Codeine administration significantly increased markers of cardiac and renal injury, as well as impaired cardiorenal functions. Codeine treatment also resulted in increased cardiac and renal malondialdehyde, Advanced Glycation Endproducts (AGE) and 8-hydroxydeoxyguanosine (8-OH-dG), and myeloperoxidase (MPO), ADA, XO, and caspase 3 activities. These observations were accompanied by impaired activities of cardiac and renal proton pumps. SIGNIFICANCE: Findings of this study demonstrate that upregulation of ADA/XO and caspase 3 signaling are, at least partly, contributory to the glucolipid deregulation and cardiorenal injury induced by codeine.

In vivo exposure to codeine induces reproductive toxicity: role of HER2 and p53/Bcl-2 signaling pathway.

Several studies have implicated codeine use in the aetiopathogenesis of male infertility. The purpose of this study was to investigate the role of HER2, Ki67, oestrogen and p53/Bcl-2 signaling pathways and the possible outcome of codeine cessation on codeine-induced reproductive toxicity. Thirty adult male Wistar rats of comparable ages and weights were randomly allocated into 5 groups. The control animals received distilled water per os (p.o), while animals in the low-dose (LDC) and high dose (HDC) codeine-treated groups received 2 and 5 mg/kg/day of codeine respectively p.o for 6 weeks. The animals in the low-dose codeine recovery (LDC-R) and high-dose codeine recovery (HDC-R) groups received treatment as LDC and HDC respectively followed by another drug-free six weeks, recovery period. Cessation of codeine exposure led to a partial reversal of codeine-induced poor sperm quality, reduced litter size and weight, increased oxidative testicular injury, testicular apoptosis, and testicular DNA damage caused by codeine administration. Codeine-induced gonado-spermotoxicity was associated with a reduction of circulatory testosterone, suppression of testicular HER2, Ki67, and Bcl-2 expression, down-regulation of oestrogen signaling, and upregulation of testicular caspase 3 activities and p53 signaling pathway. Conclusion: Upregulation of oestrogen signaling associated with enhanced testicular HER2 and Ki67 expression during the recovery period is seemingly beneficial in protecting against codeine-related testicular injury and infertility.

Codeine-induced hepatic injury is via oxido-inflammatory damage and caspase-3-mediated apoptosis.

Codeine (3-methylmorphine) is a known analgesic, antitussive, and antidiarrheal drug that is often abused for recreational purposes. It is metabolized in the liver via the cytochrome P450 system and thus hypothesized to induce hepatic injury especially when misused. Thus, the present study aimed at investigating changes in liver function, hepatic enzyme biomarker, proton pumps, antioxidant status, free radicals and TNF-α levels, as well as caspase 3 activities and hepatic DNA fragmentation after 6 weeks of oral codeine administration. Twenty-one male rabbits were randomized into 3 groups (n = 7). The control group had 1 ml of normal saline, while the low-dose and high-dose codeine groups received 4 and 10 mg/kg b.w of codeine respectively daily. The codeine-treated animals had significantly lower levels of serum proteins, increased activities of hepatic enzyme biomarkers and caspase 3, raised hepatic concentrations of free radicals and TNF-α, as well as increased hepatic DNA fragmentation. Codeine treatment also led to a significant decline in hepatic weight, activities of hepatic enzymatic antioxidant, Na+-K+-ATPase and Ca2+-ATPase. These alterations were more pronounced in high-dose codeine treated animals than in the low-dose group. Histopathological study showed moderate fatty degeneration of hepatic parenchyma, infiltration of the portal tract by inflammatory cells with dense collagen fibre deposition in codeine-treated animals. The present study revealed that codeine induced liver injury and hepatic DNA damage via caspase 3-dependent signaling by suppressing hepatic antioxidant status and enhancing free radical and TNF-α generation.

Assessment of sexual behaviour and fertility indices in male rabbits following chronic codeine use.

BACKGROUND: Codeine is the latest trend of drug abuse, particularly in Nigeria and regarded as the gateway to the abuse of other substances. OBJECTIVES: The present study examined the effects of graded doses of codeine on sexual behaviour and fertility profile. MATERIALS AND METHODS: Rabbits were either administered normal saline (0.2 mL), 4mg/kg b.w of codeine (low dose), or 10mg/kg b.w of codeine (high dose) p.o for 6 weeks. RESULTS AND DISCUSSION: Findings of the study showed that codeine administration significantly increased libido as witnessed by significantly short mount latency (ML), intromission latency (IL), post-ejaculatory interval (PEI) and significantly increased mount frequency (MF), intromission frequency (IF) and ejaculation latency (EL). Furthermore, codeine caused a marked rise in penile reflexes evident by a significant increase in erections, quick flips, long flips and total penile reflexes. However, copulatory efficiency and fertility index were significantly lower in codeine-treated groups when compared with the control. Serum levels of testosterone were also significantly lower in the treated groups. CONCLUSIONS: The present study demonstrates that codeine-induced enhancement of sexual performance is via a testosterone-independent mechanism. It also reveals that although codeine enhances copulatory locomotor activity, it is a potential risk factor for infertility.

Trona Causes Fetal Loss in Pregnant Rat via an Oestrogen-dependent Mechanism.

BACKGROUND: There is a claim in folklore medicine in Nigeria that trona (a sesquicarbonate or hydrated carbonate of sodium) causes fetal loss. However, this has not been substantiated or refuted by any scientific evidence. AIM: This study evaluates whether or not trona causes fetal loss in pregnant female Wistar rats. METHODS: Pregnant Wistar rats of comparable weights were randomized into three groups. Group A (control) was given a single dose of 1.25 mL/kg body weight of lime while groups B and C were given 250 mg/kg and 500 mg/kg body weight of trona, respectively. RESULTS: There was no significant difference in the body weight gained across all the groups. The dose of 250 mg/kg body weight of trona decreased the number of live fetus, while 500 mg/kg body weight produced no live fetus; 250 mg/kg and 500 mg/kg body weight of trona led to fetal loss rate of 83.33% and 100%, respectively. Trona also reduced the concentrations of serum progesterone and cholesterol, and increased serum oestradiol. CONCLUSION: This study revealed that trona causes fetal loss. This is possibly via an oestrogen-dependent mechanism, and attributed to the chemical constituents of trona.

Hypothalamic-pituitary-ovarian Axis in Thyroid Dysfunction.

BACKGROUND: It has been established that thyroid dysfunction causes impairment of reproductive function. However, laboratory and human studies that associated this with female reproductive hormones are conflicting and data reporting the effects of thyroid dysfunction on reproductive organs are insufficient. AIM: This study investigated the effect of experimental hypothyroidism and hyperthyroidism on hypothalamic-pituitary-ovarian axis and reproductive organs morphometry and histology in female rats. METHODS: Laboratory animals were randomized into one of the three groups: control, carbimazole-induced hypothyroidism and levothyroxine-induced hyperthyroidism. RESULTS: Organ morphometry and serum follicle stimulating hormone (FSH) were statistically comparable across all groups. Serum progesterone increased in hypothyroid rats but was reduced in hyperthyroid rats when compared with the control (p < 0.05). Body weight gain, serum luteinizing hormone and oestradiol were significantly reduced in both hypothyroid and hyperthyroid states when compared to the control. Hypothyroidism and hyperthyroidism also led to alterations in organ cytoarchitecture. CONCLUSION: Findings from this study suggest that impairment of reproductive function associated with thyroid dysfunction is attendant with derangement of hormonal milieu and alteration in reproductive organs cytoarchitecture. Luteinizing hormone and oestradiol are implicated.

Effect of ethanolic extract of Cryptolepis sanguinolenta stem on in vivo and in vitro glucose absorption and transport: Mechanism of its antidiabetic activity.

OBJECTIVE: Extracts from various morphological parts of Cryptolepis sanguinolenta are widely used traditionally in folklore medicine in many parts of the world for the management, control, and/or treatment of a plethora of human ailments, including diabetes mellitus. In order to scientifically appraise some of the ethnomedical uses of Cryptolepis sanguinolenta, the present study was undertaken to investigate its influence at varying doses on intestinal glucose absorption and transport in relation to its hypoglycemic and hypolipidemic effects in rat experimental paradigms. MATERIALS AND METHODS: The animals used were divided into four groups. Control animals received 2 ml of distilled water, while treated groups received 50, 150, and 250 mg/kg bw of Cryptolepis sanguinolenta extract per oral respectively daily for 21 days. RESULTS: Cryptolepis sanguinolenta led to a significant decrease in glucose transport and absorption. It also caused significant reductions in plasma glucose, total cholesterol, triglyceride, and LDL cholesterol. Biochemical changes observed were suggestive of dose dependence. Histopathological studies also showed increased sizes of ß cells of the pancreas. CONCLUSION: The findings in these normoglycemic laboratory animals suggest that Cryptolepis sanguinolenta has hypoglycemic and hypolipidemic activities, possibly by reducing glucose absorption and transport, and enhancing the structural and functional abilities of the ß cells. This is the first study to report the effect of Cryptolepis sanguinolenta on intestinal glucose absorption. This effect could be attributed to its major bioactive principle, cryptolepine, an indoloquinoline alkaloid. This study thus lends credence to the use of Cryptolepis sanguinolenta in the management of diabetes mellitus.