Penile erection and cardiovascular function: effects and pathophysiology.

Penile erection (PE) is a hemodynamic event that results from a neuroendocrine process, and it is influenced by the cardiovascular status of the patient. However, it may also modulate an individual's cardiovascular events. The present study provides the mechanisms involved in the association of PE and cardiovascular function. Erection upsurges the cardiac rate, blood pressure, and oxygen uptake. Sex-enhancing strategies, such as phosphodiesterase inhibitors, alprostadil, and testosterone also promote vasodilatation and cardiac performance, thus preventing myocardial infarction. More so, drugs that are used in the treatment of hypertensive heart diseases (such as angiotensin system inhibitors and ß-blockers) facilitate vasodilatation and PE. These associations have been linked with nitric oxide- and testosterone-dependent enhancing effects on the vascular endothelium. In addition, impaired cardiovascular function may negatively impact PE; therefore, impaired PE may be a pointer to cardiovascular pathology. Hence, evaluation of the cardiovascular status of an individual with erectile dysfunction (ED) is essential. Also, employing strategies that are used in maintaining optimal cardiac function may be useful in the management of ED.

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.

Zinc improves sexual and erectile function in HAART-treated rats via the upregulation of erectogenic enzymes and maintenance of redox balance.

PURPOSE: HAART has been shown to impair sexual function and penile erection via perturbation of penile redox balance, while zinc has been established to exert antioxidant activity. Therefore, this study focused on the role and associated molecular mechanism of zinc in HAART-induced sexual and erectile dysfunction. MATERIALS AND METHODS: Twenty male Wistar rats were randomly grouped into four (n = 5 rats per group); the control, zinc-treated, HAART-treated, and HAART + zinc-treated groups. Treatments were per os daily for eight weeks. RESULTS: Zinc co-administration significantly improved HAART-induced increase in the latencies of mount, intromission, and ejaculations. Zinc also attenuated HAART-induced reduction in the motivation to mate, penile reflex/erection, and frequencies of mount, intromission, and ejaculations. In addition, zinc co-treatment improved HAART-induced decline in penile NO and cGMP, dopamine, and serum testosterone. More so, zinc prevented HAART-induced rise in penile activities of monoamine oxidase, acetylcholinesterase, phosphodiesterase-5, and arginase. Furthermore, concomitant treatment with zinc ameliorated HAART-induced penile oxidative stress and inflammation. CONCLUSION: In conclusion, our present findings show that zinc improves sexual and erectile function in HAART-treated rats by upregulating erectogenic enzymes via the maintenance of penile redox balance.

Zinc protects against lead-induced testicular damage via modulation of steroidogenic and xanthine oxidase/uric acid/caspase 3-mediated apoptotic signaling in male Wistar rats.

AIM: This study evaluated the effect of lead, with or without zinc co-administration, on steroidogenic and xanthine oxidase (XO)/uric acid (UA)/caspase 3-mediated apoptotic signaling in the testis. MATERIALS AND METHODS: Forty male Wistar rats were divided into four groups at random; vehicle-treated control, zinc-treated, lead-treated, and lead + zinc-treated groups. RESULTS: Lead exposure significantly lowered overall weight gain, testicular, epididymal, seminal vesicle, and prostate weights. Also, lead decreased sperm count, viability and motility but increased the fraction of sperm with aberrant morphology. In addition, lead caused a marked rise in the level of UA and XO activity but a decrease in nuclear factor erythroid 2-related factor 2 (Nrf2), reduced glutathione (GSH) as well as total antioxidant capacity (TAC) levels, and superoxide dismutase (SOD) and catalase activities. Furthermore, lead increased the testicular levels of nuclear factor kappa B (NFkB), interleukin-1beta (IL-1ß), and tumour necrotic factor-alpha (TNF-α), which were associated with an increase in testicular caspase 3 activity and DNA fragmentation as well as a decline in circulating gonadotropin releasing hormone (GnRH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and testicular 3ß-hydroxysteroid dehydrogenase (3ß-HSD) and 17ß-hydroxysteroid dehydrogenase (17ß-HSD). These were associated with lead-induced degenerative changes in testicular tissues evidenced by shrunken seminiferous tubules, degeneration and sloughing of germ cells. Co-administration of zinc prevented lead-induced testicular injury by ameliorating oxidative stress, apoptosis, and inflammation through downregulation of XO/UA/caspase 3 pathway and upregulation of testicular 3ß-HSD/17ß-HSD. CONCLUSION: This study demonstrated that zinc protected against lead-induced testicular toxicity via the downregulation of XO/UA/caspase 3 signaling.

Impact of COVID 19 on erectile function.

Purpose: COVID-19, a novel infection, presented with several complications, including socioeconomical and reproductive health challenges such as erectile dysfunction (ED). The present review summarizes the available shreds of evidence on the impact of COVID-19 on ED.Materials and methods: All published peer-reviewed articles from the onset of the COVID-19 outbreak to date, relating to ED, were reviewed. Results: Available pieces of evidence that ED is a consequence of COVID-19 are convincing. COVID-19 and ED share common risk factors such as disruption of vascular integrity, cardiovascular disease (CVD), cytokine storm, diabetes, obesity, and chronic kidney disease (CKD). COVID-19 also induces impaired pulmonary haemodynamics, increased ang II, testicular damage and low serum testosterone, and reduced arginine-dependent NO bioavailability that promotes reactive oxygen species (ROS) generation and endothelial dysfunction, resulting in ED. In addition, COVID-19 triggers psychological/mental stress and suppresses testosterone-dependent dopamine concentration, which contributes to incident ED.Conclusions: In conclusion, COVID-19 exerts a detrimental effect on male reproductive function, including erectile function. This involves a cascade of events from multiple pathways. As the pandemic dwindles, identifying the long-term effects of COVID-19-induced ED, and proffering adequate and effective measures in militating against COVID-19-induced ED remains pertinent.

Co-administration of HAART and antikoch triggers cardiometabolic dysfunction through an oxidative stress-mediated pathway.

BACKGROUND: Antikoch and highly active anti-retroviral therapy are effective drugs in the management of tuberculosis and Human Immunodeficiency Virus, respectively. However, these cocktails have been independently associated with the aetiopathogenesis of metabolic syndrome. This study investigated whether or not the co-administration of antikoch and anti-retroviral, as seen in tuberculosis/Human Immunodeficiency Virus co-infection, will produce a similar effect. Also, it evaluated the role of glutathione and adenine deaminase/xanthine oxidase/uric acid signaling in antikoch/anti-retroviral-induced cardiometabolic dysfunction. METHODS: Male rats of Wistar strain were randomized into four groups: the control, which had 0.5 mL of distilled water as a vehicle, anti-Koch-treated rats that were administered a cocktail of anti-Koch, HAART-treated rats that had a combination of anti-retroviral drugs, and anti-Koch + HAART-treated rats that had treatments as anti-Koch-treated and HAART-treated rats. The treatment was once daily and lasted for eight weeks. One way-analysis of variance followed by Tukey's posthoc test was used to test for significance and pairwise comparisons respectively. RESULTS: Although no changes in body weight gain and cardiac weight were noted, it was found that antikoch and/or HAART caused insulin resistance and elevated blood glucose level. In addition, antikoch and/or HAART led to dyslipidaemia, increased atherogenic indices, and elevated cardiac injury markers. These were accompanied by increased plasma and cardiac concentrations of malondialdehyde and nitric oxide, C-reactive protein, and myeloperoxidase activity, as well as suppressed activities of glutathione peroxidase and glutathione-S-transferase, and a fall in reduced glutathione level. The observed alterations were more pronounced in animals that received a combination of antikoch and HAART. CONCLUSIONS: This study provides the first evidence that antikoch and/or HAART induce cardiometabolic dysfunction via glutathione suppression and up-regulation of adenine deaminase/xanthine oxidase/uric acid-dependent oxidative stress and inflammatory response. These events were associated with dyslipidaemia and increased atherogenic indices. This infers that regular monitoring of glucose level, insulin sensitivity, lipid profile, and oxido-inflammatory markers is important in patients on antikoch and/or HAART for prompt diagnosis and management of cardiometabolic disorder if it ensues.

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.

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.

Metabolic Derangement by Arsenic: a Review of the Mechanisms.

Studies have implicated arsenic exposure in various pathological conditions, including metabolic disorders, which have become a global phenomenon, affecting developed, developing, and under-developed nations. Despite the huge risks associated with arsenic exposure, humans remain constantly exposed to it, especially through the consumption of contaminated water and food. This present study provides an in-depth insight into the mechanistic pathways involved in the metabolic derangement by arsenic. Compelling pieces of evidence demonstrate that arsenic induces metabolic disorders via multiple pathways. Apart from the initiation of oxidative stress and inflammation, arsenic prevents the phosphorylation of Akt at Ser473 and Thr308, leading to the inhibition of PDK-1/Akt insulin signaling, thereby reducing GLUT4 translocation through the activation of Nrf2. Also, arsenic downregulates mitochondrial deacetylase Sirt3, decreasing the ability of its associated transcription factor, FOXO3a, to bind to the agents that support the genes for manganese superoxide dismutase and PPARg co-activator (PGC)-1a. In addition, arsenic activates MAPKs, modulates p53/ Bcl-2 signaling, suppresses Mdm-2 and PARP, activates NLRP3 inflammasome and caspase-mediated apoptosis, and induces ER stress, and ox-mtDNA-dependent mitophagy and autophagy. More so, arsenic alters lipid metabolism by decreasing the presence of 3-hydroxy-e-methylglutaryl-CoA synthase 1 and carnitine O-octanoyl transferase (Crot) and increasing the presence of fatty acid-binding protein-3 mRNA. Furthermore, arsenic promotes atherosclerosis by inducing endothelial damage. This cascade of pathophysiological events promotes metabolic derangement. Although the pieces of evidence provided by this study are convincing, future studies evaluating the involvement of other likely mechanisms are important. Also, epidemiological studies might be necessary for the translation of most of the findings in animal models to humans.

Sodium acetate ameliorates doxorubicin-induced cardiac injury via upregulation of Nrf2/HO-1 signaling and downregulation of NFkB-mediated apoptotic signaling in Wistar rats.

Despite the effectiveness of doxorubicin (DOX) in the management of a wide range of cancers, a major challenge is its cardio-toxic effect. Oxidative stress, inflammation, and apoptosis are major pathways for the cardiotoxic effect of DOX. On the other hand, acetate reportedly exerts antioxidant, anti-inflammatory, and anti-apoptotic activities. This particular research assessed the impact of acetate on cardiotoxicity induced by DOX. Mechanistically, acetate dramatically inhibited DOX-induced upregulation of xanthine oxidase and uric acid pathway as well as downregulation of Nrf2/HO-1 signaling and its upstream proteins (reduced glutathione peroxidase, superoxide dismutase, glutathione-S-transferase, glutathione, and catalase, glutathione reductase). In addition, acetate markedly attenuated DOX-driven rise inTNF-α, NFkB IL-6 and IL-1ß expression, and myeloperoxidase activity. Furthermore, acetate significantly ameliorated DOX-led suppression of Bcl-2 and Ca2+-ATPase activity and upregulation of Bax, caspase 3, and caspase 9 actions. Improved body weight, heart structural integrity, and cardiac function as depicted by cardiac injury markers convoyed these cascades of events. Summarily, the present study demonstrated that acetate protects against DOX-induced cardiotoxicity by upregulating Nrf2/HO-1 signaling and downregulating NFkB-mediated activation of Bax/Bcl-2 and caspase signaling.

Regulatory Involvement of Kisspeptin in Energy Balance and Reproduction.

The hypothalamic-pituitary-gonadal axis, which regulates steroidogenesis and germ cell formation, closely regulates the reproduction process. Nonetheless, other chemical mediators, such as kisspeptin, influence this axis. Kisspeptin is a hypothalamic neuropeptide that modulates the function of this axis and also plays a central role in energy balance. The present study reviews the impact and associated mechanisms of kisspeptin on male and female reproduction based on available evidence in the literature. Kisspeptin and its neurons exert anorexigenic activity, thus maintaining adequate energy balance for optimal reproductive function. Also, they stimulate the release of GnRH, resulting in the optimal performance of gonadal physiological processes viz. production of steroid sex hormones and germ cells. However, studies linking kisspeptin to reproduction are yet scanty. Hence, studies exploring the upstream and downstream signaling pathways activated by kisspeptin concerning reproduction in an attempt to better understand the associated mechanisms of the regulatory activities of kisspeptin on reproduction are recommended. In addition, potential factors that may modulate kisspeptin activities may be useful in the management of infertility and perhaps, in the development of contraceptives for those who do not intend to achieve conception.

SARS-CoV-2 impairs male fertility by targeting semen quality and testosterone level: A systematic review and meta-analysis.

BACKGROUND: Since the discovery of COVID-19 in December 2019, the novel virus has spread globally causing significant medical and socio-economic burden. Although the pandemic has been curtailed, the virus and its attendant complication live on. A major global concern is its adverse impact on male fertility. AIM: This study was aimed to give an up to date and robust data regarding the effect of COVID-19 on semen variables and male reproductive hormones. MATERIALS AND METHODS: Literature search was performed according to the recommendations of PRISMA. Out of the 852 studies collected, only 40 were eligible for inclusion in assessing the effect SARS-CoV-2 exerts on semen quality and androgens. More so, a SWOT analysis was conducted. RESULTS: The present study demonstrated that SARS-CoV-2 significantly reduced ejaculate volume, sperm count, concentration, viability, normal morphology, and total and progressive motility. Furthermore, SARS-CoV-2 led to a reduction in circulating testosterone level, but a rise in oestrogen, prolactin, and luteinizing hormone levels. These findings were associated with a decline in testosterone/luteinizing hormone ratio. CONCLUSIONS: The current study provides compelling evidence that SARS-CoV-2 may lower male fertility by reducing semen quality through a hormone-dependent mechanism; reduction in testosterone level and increase in oestrogen and prolactin levels.

Sodium acetate abates lead-induced sexual dysfunction by upregulating testosterone-dependent eNOS/NO/cGMP signaling and activating Nrf2/HO-1 in male Wistar rat.

Oxidative stress has been linked with lead toxicity, including lead-induced sexual dysfunction. On the contrary, sodium acetate has been proven to exert antioxidant activity. However, the effect of sodium acetate on lead-induced sexual dysfunction has not been fully explored. This study investigated the effect of sodium acetate on lead-induced sexual dysfunction, exploring the involvement of testosterone, eNOS/NO/cGMP, and Nrf2/HO-1 signaling. Twenty male Wistar rats with similar weights were randomly assigned into four groups (n = 5 rats/group) after two weeks of acclimatization. Animals were vehicle-treated (0.5 ml/day of distilled water, per os), acetate-treated (200 mg/kg/day, per os), lead-treated (20 mg/kg/day, per os), or lead + acetate-treated. The results revealed that sodium acetate treatment attenuated lead-induced rise in penile lead, malondialdehyde and oxidized glutathione concentrations, and acetylcholinesterase activity. In addition, lead exposure prolonged mount, intromission, and ejaculation latency and reduced mount, intromission, and ejaculation frequency, as well as the motivation to mate and penile reflex, which were improved by acetate treatment. More so, acetate treatment ameliorated lead-induced reductions in absolute and relative penile weight, eNOS, NO, cGMP, luteinizing hormone, follicle-stimulating hormone, testosterone, dopamine, Nrf2, HO-1, and reduced glutathione concentrations, as well as glutathione reductase, glutathione peroxidase, glutathione-S-transferase, superoxide dismutase, and catalase activities. In conclusion, this study demonstrates that sodium acetate attenuated lead-induced sexual dysfunction by upregulating testosterone-dependent eNOS/NO/cGMP and Nrf2/HO-1 signaling. Despite the compelling data presented in this study, other possible associated mechanisms in the protective role of acetate should be explored.

Pathophysiology and management of testicular ischemia/reperfusion injury: Lessons from animal models.

Testicular torsion is a urological emergency that involves the twisting of the spermatic cord along its course. Compelling pieces of evidence have implicated oxidative stress-sensitive signaling in pathogenesis of testicular I/R injury. Although, surgical detorsion is the mainstay management; blockade of the pathways involved in the pathogenesis may improve the surgical outcome. Experimental studies using various testicular I/R models have been reported in a bid to explore the mechanisms associated with testicular I/R and evaluate the benefits of potential therapeutic measures; however, most are limited by their shortcomings. Thus, this review was intended to describe the details of the available testicular I/R models as well as their merits and drawbacks, the pathophysiological basis and consequences of testicular I/R, and the pharmacological agents that have being proposed to confer testicular benefits against testicular I/R. This provides an understanding of the pathophysiological events and available models used in studying testicular I/R. In addition, this research provides evidence-based molecules with therapeutic potentials as well as their mechanisms of action in testicular I/R.

Sexual dysfunction in dichlorvos-exposed male Wistar rat is ameliorated by curcumin and associated with the upregulation of testosterone.

Dichlorvos is an organophosphate pesticide that is commonly used for agricultural and domestic control of pests and insects. Despite its usefulness, it exerts reproductive toxicity and induces male sexual dysfunction. On the other hand, curcumin has been reported to improve sexual dysfunction. However, till date, no study has reported the impact of curcumin on dichlorvos-induced sexual dysfunction. This study investigated the effect and associated mechanism of curcumin on dichlorvos-induced sexual dysfunction. Thirty-two male Wistar rats were randomized into four groups; the control (1 mL of olive oil), curcumin-treated (100 mg/kg), DDVP-treated (98.54 g/m3 of dichlorvos by inhalation), and DDVP + Curcumin-treated. Dichlorvos induced sexual dysfunction as depicted by reduced motivation to mate (8.38 ± 0.18 vs. 4.00 ± 0.33, P < 0.0001), prolonged latencies (46.63 ± 1.30 vs. 98.75 ± 1.32, P < 0.0001) and reduced frequencies of mount (14.88 ± 0.52 vs. 8.63 ± 0.38), intromission (9.38 ± 0.50 vs. 3.75 ± 0.31, P < 0.0001), and ejaculation (7.63 ± 0.38 vs. 1.50 ± 0.19, P < 0.0001). These findings were accompanied by suppression of hypothalamic-pituitary-testicular axis, evidenced by marked reductions in circulating FSH (60.00 ± 1.04 vs. 21.13 ± 0.52, P < 0.0001), LH (46.38 ± 1.38 vs. 19.00 ± 0.46, P < 0.0001), and testosterone (6.01 ± 0.50 vs. 0.74 ± 0.05, P < 0.0001). Nonetheless, the administration of curcumin in dichlorvos-exposed rats significantly attenuated dichlorvos-induced sexual dysfunction by improving the assessed indices of male sexual act. Also, curcumin significantly increased serum levels of FSH (21.13 ± 0.52 vs. 47.25 ± 0.10, P < 0.0001), LH (19.00 ± 0.46 vs. 43.00 ± 1.49), and testosterone (0.74 ± 0.05 vs. 3.98 ± 0.08, P < 0.0001). This study revealed that curcumin attenuated dichlorvos-induced sexual dysfunction by activating the hypothalamic-pituitary-testicular axis and upregulating circulating testosterone.

L-arginine attenuates dichlorvos-induced testicular toxicity in male Wistar rats by suppressing oxidative stress-dependent activation of caspase 3-mediated apoptosis.

BACKGROUND: The continuous use of pesticides, such as dichlorvos, is a common agricultural and domestic practice. However, it is associated with shortfalls like testicular toxicity through the induction of oxidative stress-mediated signaling. On the other hand, L-arginine, a precursor of nitric oxide, has been reported to exert antioxidant activities and thus may attenuate dichlorvos-induced testicular toxicity. AIM: Hence, this study was designed to evaluate the effect of L-arginine treatment on dichlorvos-induced testicular toxicity. MATERIALS AND METHODS: Forty male Wistar rats were randomly assigned into four equal groups. The control rats were administered 0.5 mL of distilled water, dichlorvos- (DDVP-) treated rats were exposed to DDVP via inhalation for 15 min, DDVP + L-arginine-treated rats were exposed to DDVP and also received 100 mg/kg b.w/day, while L-arginine-treated rats received 100 mg/kg b.w/day. RESULTS: DDVP exposure significantly reduced testicular nitric oxide, relative testicular weight, lowered sperm count, viability, and motility, and suppressed serum FSH, LH, and testosterone levels. These findings were associated with a rise in testicular malondialdehyde, TNF-α, IL-6, and 8OHdG levels and caspase 3 activities, and a reduction in GSH and superoxide dismutase. Additionally, on histopathological examination, DDVP was observed to reduce mature sperm cells in the seminiferous tubular lumen and induce focal vascular congestion in the interstitial space. Nonetheless, L-arginine treatment significantly attenuated DDVP-induced biochemical and histological alterations. CONCLUSION: This study showed that L-arginine attenuated testicular toxicity by improving epididymal sperm variables and male sex hormones by suppressing oxidative stress, inflammation, and apoptosis in DDVP-exposed rats.

Acetate attenuates cyclophosphamide-induced cardiac injury via inhibition of NF-kB signaling and suppression of caspase 3-dependent apoptosis in Wistar rats.

AIM: The goal of the current study was to examine the potential therapeutic effects of sodium acetate on cardiac toxicities caused by cyclophosphamide in Wistar rats. The possible involvement of NF-kB/caspase 3 signaling was also explored. MAIN METHODS: Thirty-two male Wistar rats were divided into four groups at random. (n = 8). The control animals received 0.5 mL of distilled water orally for 14 days, the acetate-treated group received 200 mg/kg/day of sodium acetate orally for 14 consecutive days, and cyclophosphamide-treated rats received 150 mg/kg /day of cyclophosphamide i.p. on day 8, while cyclophosphamide + acetate group received sodium acetate and cyclophosphamide as earlier stated. KEY FINDINGS: Results showed that cyclophosphamide-induced cardiotoxicity, which manifested as a marked drop in body and cardiac weights as well as cardiac weight/tibial length, increased levels of troponin, C-reactive protein, lactate, and creatinine kinase, and lactate dehydrogenase activities in the plasma and cardiac tissue. Histopathological examination also revealed toxic cardiac histopathological changes. These alterations were associated with a significant increase in xanthine oxidase and myeloperoxidase activities, uric acid, malondialdehyde, TNF-α, IL-1ß, NFkB, DNA fragmentation, and caspase 3 and caspase 9 activities in addition to a marked decline in Nrf2 and GSH levels, and SOD and catalase activities in the cardiac tissue. Acetate co-administration significantly attenuated cyclophosphamide cardiotoxicity by its antioxidant effect, preventing NFkB activation and caspase 9/caspase 3 signalings. SIGNIFICANCE: This study shows that acetate co-administration may have cardio-protective effects against cyclophosphamide-induced cardiotoxicity by inhibiting NF-kB signaling and suppressing caspase-3-dependent apoptosis.

Comparison of the effectiveness of levonorgestrel intrauterine system and dienogest in the management of adenomyosis: A systematic review and meta-analysis.

BACKGROUND: Adenomyosis is a gynaecological lesion that impairs female fertility and contributes to reduced quality of life. There are several surgical and medical options for the management of this lesion; however, women who wish to conceive opt for medical therapies such as the levonorgestrel intrauterine device (LNG-IUS) and dienogest, which have various outcomes. To date, there is no consensus regarding which is more effective. OBJECTIVES: To compare the effectiveness of LNG-IUS and dienogest for the management of adenomyosis, and explore the risk of occurrence of known side effects for both treatments. DESIGN: Systematic review and meta-analysis exploring the effectiveness of LNG-IUS and dienogest for the management of adenomyosis. METHODS: A literature search was conducted using PICO guidelines and EMBASE, PubMed/MEDLINE, Scopus and Web of Science databases. Only clinical trials were collected and analysed. RESULTS: Of the 792 studies that were initially identified, six were eligible for inclusion in this study. The studies included a total of 707 women; of these, 270 were treated with LNG-IUS, 354 were treated with dienogest, and 83 were controls. All the studies were from Asia (Bangladesh n = 1, China n = 2, India n = 1, Japan n = 1, South Korea n = 1). Dienogest was found to reduce pelvic pain significantly, evidenced by a lower visual analogue scale score, compared with LNG-IUS. Also, dienogest led to a significant reduction in uterine volume compared with LNG-IUS. However, subjects in the LNG-IUS group had significantly higher levels of haemoglobin than those in the dienogest group. Nonetheless, the occurrence of side effects such as weight gain, breast tenderness/distension, headache, insomnia/sleep disorder, depression/mood disorder, skin disorder/acne, and coital discomfort/reduced libido were comparable in both treatment groups. CONCLUSION: Dienogest may be more effective than LNG-IUS for the management of adenomyosis, as it shows a superior effect in the reduction of pelvic pain and uterine volume. As only six studies were included in the present meta-analysis due to the paucity of data in the literature, it is recommended that well-designed randomized controlled trials comparing the effectiveness of dienogest with LNG-IUS should be conducted.

Impact of arsenic on male and female reproductive function: a review of the pathophysiology and potential therapeutic strategies.

Arsenic is a ubiquitous metalloid and heavy metal that contributes to the global decline in human fertility. Humans are constantly exposed to arsenic through biotic and abiotic sources, especially ingestion of arsenic-contaminated food and water. Its exposure is associated with several adverse health challenges, including reproductive toxicity. In spite of its reported adverse effects, arsenic exposure remains a global challenge. Hence, this study provides a comprehensive review of the literature on the impact and mechanism of arsenic on male and female reproductive function. Additionally, a review of the potential therapeutic strategies is presented. Evidence from the literature reveals that arsenic upregulates reactive oxygen species (ROS) generation which mediates arsenic-induced suppression of the hypothalamic-pituitary-gonadal axis and inactivation of 3ß-HSD and 17ß-HSD activities, leading to reduced gonadal steroidogenesis. Through several oxidative stress-dependent signaling, arsenic induces the apoptosis of the germ cells, thus contributing to the development of infertility. At the moment, there is no specific treatment for arsenic-induced reproductive toxicity. However, increasing data form the scientific literature reveals the benefits of antioxidants in ameliorating arsenic-induced reproductive toxicity. These molecules suppress ROS generation and maintain optimal activities of the hypothalamic-pituitary-gonadal axis, leading to optimal steroidogenesis and gametogenesis as well as improved germ cells. Overall, this study revealed the impact and associated mechanism of arsenic-induced reproductive toxicity. It also provides evidence from the literature demonstrating potential therapeutic measures in managing arsenic-induced reproductive toxicity.

Common onion (Allium cepa) extract reverses cadmium-induced organ toxicity and dyslipidaemia via redox alteration in rats.

BACKGROUND: Cadmium (Cd) remains an important environmental pollutant of public health concern as it causes organ toxicity, and cardiovascular diseases (CVD), but the roles of common foods such as onion (Allium cepa) need further clarification. The aims of this study were to clarify whether or not Cd-induced organ dysfunction was associated with blood protein, lipid and lipid peroxidation and the effects of onion extract AcE in a rat model. METHODS: Control and Cd-treated rats were maintained on control diet, while AcE+Cd-treated rats were also orally administered AcE (1ml/100g body weight). Cd-treated and AcE+Cd-treated rats also received cadmium as CdSO4 (1.5ml/kg body weight of 0.3mg/L of CdSO4) via drinking water. RESULTS: It was found that Cd significantly increased total cholesterol, triglycerides, LDL-cholesterol, serum albumin, and reduced HDL-cholesterol, total plasma protein, and plasma testosterone. Administration of AcE restored the liver and kidney toxicities and blood protein and lipid profiles. Moreover, AcE improved Cd-induced decrease in urinary volume and renal clearance, and also protected against Cd-induced oxidative stress by normalizing redox status. However, AcE did not affect Cd-induced altered plasma testosterone. CONCLUSION: Our study suggests that Cd-induced CVD was associated with altered blood dysproteinemia, dyslipidaemia, and oxidative stress. It also provided the first evidence of the therapeutic efficacy of AcE against atherosclerotic conditions and organ toxicity in Cd-intoxicated rats via a mechanism independent of the circulating testosterone level.