Arjunolic acid reverses fluoxetine-induced alterations in testicular steroidogenic enzymes and membrane bound ionic pump imbalance through suppression of oxido-inflammatory stress and apoptosis.

OBJECTIVE: The impact of the anti-depressant therapy on gonadal function has been recognized and discussed over the years. However, data to supplement our understanding of the impact of arjunolic acid (AA) therapies in protecting against FXT-induced gonadal dysfunction is lacking clear scientific evidence. Hence, this study aimed to investigate the possible effect of AA on fluoxetine-induced altered testicular function in rats. METHODS: After 14 days acclimatization, Thirty-six (36) adult male rats were randomly divided into 6 groups (n=6). Rats in groups 1 received normal saline (10mL/kg); groups 2 & 3 were given AA (1.0mg/kg body weight) and AA (2.0mg/kg body weight), respectively; whereas, rats in group 4 were given FXT (10mg/kg/p.o/day), and groups 5 & 6 were given a combination of FXT (10mg/kg) + AA (1.0mg/kg body weight); and FXT (10mg/kg) + AA (2.0mg/kg body weight), respectively. RESULTS: The results shows that FXT significantly altered testicular steroidogenic enzymes (3ß-HSD and 17ß-HSD) and proton pump ATPase (Na+/K+ ATPase, Ca2+ ATPase and H+ ATPase) activities, as well as testicular architecture when compared with controls. More so, FXT caused oxido-inflammation and apoptosis, as evidence by increases in MDA, MPO, TNF-α, IL-1ß, Caspase 3 and p53. However, AA at a different dose significantly ameliorated the destructive impacts of FXT on steroidogenic enzymes, proton pump ATPase as well as increased Bcl-2, SOD, CAT, GSH and improved testicular architecture in rats. CONCLUSIONS: AA reverses fluoxetine-induced alterations in testicular steroidogenic enzymes and membrane-bound ionic pump through suppression of oxido-inflammatory stress and apoptosis.

Epigallocatechin-gallate attenuates rapamycin exacerbated high fat diet-induced autophagy, hormonal dysregulation, testicular and brain oxidative stress, and neurochemical changes in rats.

This study investigated whether epigallocatechin-gallate (EGCG) could counteract the detrimental effects of high-fat diet (HFD)-induced obesity in rats exposed to rapamycin-induced reproductive and neuronal changes. Six rats per treatment group (n = 6) were utilized, in which groups 1 and 2 had dimethylsulfoxide (DMSO) (0.1%) and EGCG (80 mg/kg) respectively. Group 3 received HFD + 0.1% DMSO daily for 56 days. Group 4 received HFD + rapamycin (1 mg/kg) orally for 56 days. Rats in group 5 received HFD for 56 days and EGCG (80 mg/kg, p.o.) from days 29-56. Group 6 received the combination of HFD + rapamycin (56 days) with EGCG (80 mg/kg) from days 29-56. Cognitive loss was assessed using Y-maze-test (YMT). Afterwards, serum sex hormones, insulin-glucose balance, serotonin concentration, acetylcholinesterase activity, sperm features, antioxidants, and the markers of oxido-nitrergic, autophagy and apoptotic mediators were assessed. EGCG reversed rapamycin exacerbated HFD-induced alterations in spermatogenesis, insulin-glucose balance, reproductive hormones, oxido-nitrergic stress, and altered serotonin, acetylcholinesterase levels, and autophagic and apoptotic activities in rats' testes and brains respectively. EGCG significantly attenuated HFD-induced cognitive loss. The study showed that EGCG attenuated rapamycin-mediated HFD-induced spermatogenesis deficiency and cognitive impairment via normalization of reproductive hormones, testicular and brain oxidative stress, apoptotic, autophagic activities, with serotonin and cholinergic levels in rats.

Underlying biochemical effects of intermittent fasting, exercise and honey on streptozotocin-induced liver damage in rats.

Purpose: Derangements of liver transcriptional factors and enzymes have important implications in diabetes-induced related complications. Hence, this study which consists of two experimental phases was aimed at evaluating the possible underlying molecular mechanisms of intermittent fasting (IF), exercise starvation and honey in streptozotocin (STZ)-mediated liver damage in diabetic rats. Methods: The diabetic rats were treated orally with distilled water (0.5 ml/kg), IF, starvation and honey at 1 g/kg body weight in the non-diabetic phase for four (4) weeks. After STZ injections, four (4) weeks of IF, exercise, starvation, and honey therapy were used as interventions prior to a biochemical evaluation of the liver. Results: IF and exercise greatly decreased liver transcription factor (resistin, SREBP-1c), inflammatory cytokines/enzyme (TNF-α, IL-6, IL-1ß, MPO) as well as oxidative and nitrergic stress with correspondence increased liver PPAR-γ, IL-10, SOD, CAT and GSH in diabetic rats unlike starvation and honey regimen relative to diabetic controls. Furthermore, IF and exercise significantly improved hepatic glycogen synthase and decreased glycogen phosphorylase in diabetic rats compared to the diabetic control group, but starvation and honey therapy had no such influence. IF and exercise strategically reduces STZ-induced liver metabolic disorder via through modulation of liver transcriptional factors and inhibition of pro-inflammatory cytokines, oxido-nitrergic and adipokine signaling pathway.

Possible mechanisms involved in the testicular-protective property of quercetin in rats exposed to endosulfan toxicity.

The study investigated the effects of quercetin and putative mechanisms involved against endosulfan-testicular impairments in rats. Rats were allotted into five treatment groups (n = 5). Groups 1-2 had normal saline and maize oil (vehicle) (10 mL/kg), group 3 received quercetin (20 mg/kg), 4-5 had endosulfan (5 mg/kg, p.o) orally for 28 days. However, from days 14-28, group 4 received an additional dose of vehicle (10 mL/kg, p.o./day), while group 5 received quercetin (20 mg/kg, p.o./day). Thereafter, blood samples and testes were harvested for markers of cholinergic, hormonal and testicular oxido-nitrergic, inflammatory, apoptosis and proton pump ATPase activities. Also, testicular histopathological changes were also evaluated alongside with germ cell count, testicular injury and spermatogenesis score. Quercetin increased testicular/body weights and spermatogenesis, androgenic hormones (follicle stimulating hormones, FSH; luteinizing hormone, LH; testosterone), acetylcholinesterase levels and attenuated altered membrane integrity, DNA fragmentation, increased caspases-3 levels in rats exposed to endosulfan. Moreover, quercetin increased testicular B-cell lymphoma-2 (Bcl-2), Bcl-2 associated x-protein (Bax) and proton pump adenosine trisphosphate (ATPase) and sialic acid levels. Of note, quercetin reversed endosulfan-mediated increased malondialdehyde, nitrite, peroxynitrite formation, 8-hydroxy-2'-deoxyguanosine and lowered antioxidant enzymes in the testes. The increased levels of testicular myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1ß) by endosulfan were also reduced by quercetin administration. Additionally, quercetin attenuate endosulfan-induced testicular histopathological changes of rats. Our findings showed that quercetin significantly inhibited endosulfan-induced testicular damage and altered spermatogenesis through inhibition of oxido-nitrergic pathway, inflammatory mediators, apoptosis, acetylcholinesterase activity and enhancement of testicular hormones and improvement in testicular ATPase activity.

d-ribose- l-cysteine abrogates testicular maladaptive responses induced by polychlorinated bisphenol intoxication in rats via activation of the mTOR signaling pathway mediating inhibition of apoptosis, inflammation, and oxidonitrergic flux.

Male reproductive maladaptive responses are becoming a global health concern and also a social issue. Polychlorinated biphenyls (PCBs) are a member of halogenated aromatic environmental pollutants with diverse environmental matrices. This study was conducted to explore the mechanisms of PCBs-induced testicular maladaptive responses and the potential reversal effects of d-ribose- l-cysteine (DRLC) on testicular injury induced by administration of PCBs (2 mg/kg) for 30 days. DRLC (50 mg/kg) was administered orally for 15 days starting from Days 16 to 30 after the initial 15 days of treatment with PCB. All assays were carried out using established protocols. Administration of DRLC at 50 mg/kg after treatment with PCBs enhances body and testicular weights, gonadotropins (luteinizing hormone and follicle-stimulating hormone), testosterone and poor sperm quality. DRLC also reduced testicular injury score, improved spermatogenesis scoring, reduced oxidative stress biomarkers (malondialdehyde), as well as restored the reduced activities of antioxidant enzymes (glutathione peroxidase, superoxide dismutase, and catalase) and decreases pro-inflammatory response (tumor necrosis factor-alpha and NO). More so, DRLC treatment abrogates testicular DNA fragmentation and downregulated p53 and caspase 3 activities and upregulated the concentration of autophagy-related protein (mammalian target of rapamycin [mTOR] and Atg7). DRLC abates testicular deficit induced by PCBs intoxicated rats via activation of the mTOR signaling pathway mediating inhibition of apoptosis, Inflammation and oxidative flux.

Immune system response to isometric handgrip exercise and effects of duration and intensity of the exercise protocol on selected immune system parameters in prehypertensives.

BACKGROUND: Recent studies have shown that physical exercise significantly modulates immunocyte dynamics and possibly plays a significant role on immune function. This study examined the responses of some selected immune system parameters to isometric handgrip exercise and identified possible effects of intensity and duration of the exercise protocols. METHODS: One hundred and ninety-two (N=192) sedentary pre-hypertensive subjects, aged between 30-50 years were recruited into the study. They were randomly distributed into three groups of 64 subjects each. A detailed explanation and a demonstration of the exercise protocol were given to the subjects and they were asked to report at the Exercise Physiology unit of the Physiotherapy department, Federal Medical Centre, Asaba, Delta State at 4.00 pm daily for the exercise practice. The training session for each day took place between the hours of 4.00 pm and 8.00 pm daily (FMC/ASB/A81.VOL.XII/101). The subjects performed a 24 consecutive day's isometric handgrip exercise at 30% Maximum Voluntary Contraction (MVC). At the end of the 24 days, group one (GP1) discontinued with the exercise protocol, while group two (GP2) and group three (GP3) continued with the exercise protocol for another 24 consecutive days nevertheless GP3 performed at an increased intensity of 50% MVC. The clinical trial was registered with Nigeria Clinical Trial Registry, Federal Ministry of Health, Abuja Nigeriawith Trial No: 1216582 (https://www.nctr.nhrec.net/viewTrials.php?TID=1216582). RESULTS: At the end of the study, the result shows thatthe number of CD4 cells and CD4/CD8 ratio significantly (P<0.05) increased while the CD8 cell decreased in GP2 and GP3. It was further shown that increase in duration produced a more significant change compared to an increase in intensity of the isometric effort. CONCLUSION: The study established that isometric handgrip exercise alters the circulating levels of the immune system parameters which could have positive beneficial effects on the prehypertensive individuals as the number of CD4 cells and CD4/CD8 ratio increased especially when practiced over a longer duration.

In Vivo Attenuation of Alcohol- and Cadmium Chloride-Induced Testicular Toxicity Modulated by Silymarin in Male Wistar Rat.

The aim of the study is to investigate the in vivo attenuation of alcohol- and cadmium chloride-induced testicular toxicity modulated by Silymarin in male Wistar rats. A total of fifty-six (56) Wistar rats were used for this study and they were randomized into seven (7) groups of eight (8) rats each. Group 1 was control rats; Groups 2-7 served as the experimental groups. After 6 weeks treatment duration, the rats were euthanized, semen was collected for semen analysis, blood samples for testosterone, and FSH and LH assay determination, and left testes was harvested for histological analysis. One-way ANOVA was used to compare means at p-level < 0.05 was considered significant. Findings from this study have shown that alcohol and cadmium chloride adversely affected semen parameters, testosterone, and FSH and LH hormone milieu. Data also showed that Silymarin administration attenuated the adverse effect of alcohol and cadmium chloride on semen quality and hormones associated with reproductive functions. Hence, Silymarin mopped the effect of in vivo attenuation of alcohol and cadmium chloride testicular damage. The findings of this study have further established that alcohol and cadmium chloride adversely affected semen parameters, testicular alterations, and serum hormonal milieu. However, the effect was more significantly deleterious in rats exposed to cadmium chloride when compared to rats exposed to alcohol, subsequently alcohol- and cadmium chloride-induced degeneration of testicular tissues. Furthermore, Silymarin administration attenuated the adverse effect of alcohol on semen quality and hormones associated with reproductive functions.

Down regulatory response of reproductive potentials in stress-induced rats supplemented with clomifene citrate: The fate of infertility.

This study was designed to physiologically investigate the fate of stress related infertility conditions to focus on the regulatory response of reproductive potentials in stress-induced female Wistar rats supplemented with clomifene citrate. 42 apparently healthy female Wistar rats weighing about 120-160 g were used in the study. The animals were randomly distributed into 3 groups after acclimatization for 2 weeks. Group 1 served as the control pregnant rats not induced by restraint, mirrored and intruder stressors, group 2 consisted of rats treated with 0.013 mg/g of clomifene citrate drug and exposed to three different stressors while group 3 represented pregnant rats exposed to different stressors but not treated with clomifene citrate. At the end of 3weeks, the rats were euthanized via cervical dislocation. The uterus and ovary organs were carefully isolated, weighed and examined for histological changes. The reproductive capacities studied were gestation period, mean pup weight, litter size and survival rate respectively. Data collected is expressed in Mean±SEM and one way ANOVA statistics was used for comparison of means while Fisher's LSD was employed for post hoc test and the level of significance is determined at p-value < 0.05. Results from our study revealed that restraint and intruder stressors following supplementation with clomifene citrate produced similar stress response in the gestation length, pub-weights, litter size and percentage of survival. Stress of different nature altered the histoarchitecture of the ovary and the uteri of rats exposed to restraint or intruder stressor. Meanwhile, Clomifene citrate administration produced effect on ovulation and pregnancy outcome of stressed pregnant rats and the survival ratio of the offspring.