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Research into the impacts of oxidative stress (OS), and hormonal balance on reproductive potential has increased over the last 40 years possibly due to rising male infertility. Decreased antioxidant levels and increased OS in tissues result from hormonal imbalance, which in turn leads to male infertility. Increased reactive oxygen species (ROS) generation in seminal plasma has been linked to many lifestyle factors such as alcohol and tobacco use, toxicant exposure, obesity, varicocele, stress, and aging. This article provides an overview of the crosslink between OS and gonadal hormone disruption, as well as a potential mode of action in male infertility. Disrupting the equilibrium between ROS generation and the antioxidant defense mechanism in the male reproductive system may affect key hormonal regulators of male reproductive activities. Unchecked ROS production may cause direct injury on reproductive tissues or could disrupt normal regulatory mechanisms of the hypothalamic-pituitary-gonadal (HPG) axis and its interaction with other endocrine axes, both of which have negative effects on male reproductive health and can lead to male infertility., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Testicular dysfunction, a major contributory factor to infertility, has received a lot of attention over the recent years. Several studies have linked abnormal sperm function and morphology with an enhanced generation of reactive oxygen species (ROS) and oxidative stress. The nuclear factor erythroid-derived 2 (Nrf2) is a transcriptional response to cellular stresses (intrinsic or extrinsic) that regulates the oxidative status, mitochondrial dysfunction, inflammation, and proteostasis. In this review, the therapeutic role of Nrf2 was explored. To do so, scientific data were retrieved from databases such as Elsevier, Wiley, Web of Science, Springer, PubMed, Taylor and Francis, and Google Scholar using search terms such as "Nrf2" and "testis," "sperm," "testicular function," and "testosterone." It has been noted that Nrf2 influences the physiology and pathology of testicular dysfunction, especially in the spermatogenic process, by regulating cellular resistance to oxidative stress, inflammation, and environmental toxicants. However, numerous compounds serve as activators and inhibitors of testicular Nrf2. Nrf2 activators might play a therapeutic role in the prevention and treatment of testicular dysfunction, while molecules that inhibit Nrf2 might induce dysfunction in testis components. Nrf2 activators protect cells against oxidative damage and activate Nrf2/KEAP1 signaling which promotes its movement to the nucleus, and increased Nrf2 function and expression, along with their downstream antioxidant gene. Nrf2 inhibitors facilitate oxidative stress via interfering with the Nrf2 signal pathway. The Nrf2 activation could serve as a promising therapeutic target for testicular dysfunction. This review explored the effect of Nrf2 on testicular function while highlighting potential activators and inhibitors of Nrf2., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The testis is an immune-privileged organ susceptible to oxidative stress and inflammation, two major factors implicated in male infertility. A reduction in the concentration and activities of testicular function biomarkers has been shown to correlate with impaired hypothalamic-pituitary-testicular axis and oxidative stress. However, the use of natural products to ameliorate these oxidative stress-induced changes may be essential to improving male reproductive function. Quercetin possesses several pharmacological activities that may help to combat cellular reproduction-related assaults, such as altered sperm function and reproductive hormone dysfunction, and dysregulated testicular apoptosis, oxidative stress, and inflammation. Studies have shown that quercetin ameliorates testicular toxicity, largely by inhibiting the generation of reactive oxygen species, with the aid of the two antioxidant pharmacophores present in its ring structure. The radical-scavenging property of quercetin may alter signal transduction of oxidative stress-induced apoptosis, prevent inflammation, and increase sperm quality in relation to the hormonal concentration. In this review, the therapeutic potential of quercetin in mediating male reproductive health is discussed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.)

The germinability and protective potential of leaf infusion of Parkia biglobosa, Moringa oleifera and Vernonia amygdalina leaves on okra (Abelmoschus esculentus) seeds against infections simulated with suspended cells of Aspergillus niger, A. flavus, A. fumigatus, and Penicillium sp. were examined. Prior to planting, the okra seeds were first surface-sterilized in 5% sodium hypochlorite solution before steeping in known concentrations (0, 20, 40, 60, 80, and 100%) of the respective leaf infusions for a known duration. Seven of the steeped seeds were planted in plastic transparent containers, incubated for 7 days under light, and observed daily. Germination index, germination rate, germination time, and vigor index were calculated for each treatment, using standard procedures. The effective concentrations of the infusions of V. amygdalina, P. biglobosa and M. oleifera were 40, 40, and 60% respectively. Optimum steeping durations in leaf infusions were 1, 5, and 6 h, for P. biglobosa, M. oleifera and V. amygdalina, respectively. All the leaf infusions were observed to protect the okra seeds against infections with the test organisms. Furthermore, seeds steeped in the respective leaf infusions showed remarkably higher germinability potential than the control seeds steeped in water. The study confirmed that the leaf infusions may be attractive as economic alternatives for seed priming and protection., (© 2022. The Author(s).)

Ethnopharmacological Relevance: Liver diseases is a public health issue in sub-saharan Africa and has been reported to be the major cause of many hospital admissions. Oxidative stress, mitochondrial dysfunction and inflammation play important roles in several diseases including liver injury. Cajanus cajan is an indigenous medicinal plant useful in the traditional treatment of jaundice, inflammation and liver injury., Aim of Study: This study assessed the effects of methanol extract Cajanus cajan (MECC) on mitochondrial permeability transition (mPT) pore opening, biomarkers of oxidative stress and inflammation in CCl 4- induced liver injury in rats., Methods: Wistar albino rats (200-210g) were completely randomized into five (5) groups of six animals each. Group I (control) was given distilled water orally once daily. Animals in group II were administered CCl 4 in parafin (1:1) at a dose of 0.5 mL/kg i.p on the seventh day. Animals in groups III, IV and V were administered methanol extract of Cajanus cajan (MECC) at doses of 100, 200 mg/kg and silymarin (100 mg/kg) respectively for 7 days prior to a single intraperitoneal dose of CCl 4 . After 24 h of CCl 4 treatment, serum and liver tissues were collected. Mitochondrial permeability transition (mPT) pore opening, mitochondrial ATPase activities and biomarkers of oxidative stress were determined spectrophotometrically. Tumor necrosis factor (TNFα), NF-κB and COX-2 were determined by immunohistochemistry and the phytochemicals present in the extract were determined by GC-MS., Results: Liver enzyme (AST, ALP, ALT and γGT) activities and MDA levels were significantly decreased in rats pretreated with MECC at the dose of 100, 200 and silymarin (100 mg/kg) when compared to the rats administered CCl 4 alone (p < 0.05). GSH, GST, CAT and SOD increased and the expressions of TNFα, NF-κB and COX- 2 were also reduced when compared to the CCl 4 - treated animals. In addition, the liver histopathological analyses revealed that MECC markedly alleviated inflammatory cell infiltration, hepatic fibrosis, hepatocyte ballooning, necrosis and severe apoptosis of hepatocytes induced by CCl 4 . GC-MS analysis yielded 23 compounds including flavonoids, terpenoids and fatty acids., Conclusion: Cajanus cajan leaf extract elicited hepatoprotective action on CCl 4 -induced liver injury via inhibition of mPT pore opening, prevention of CCl 4 -induced hepatic oxidative stress and suppression of inflammatory response thus it may become useful for chemoprevention of liver injury. This supports its traditional use., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Alcoholism has been linked to problems with male reproductive function. The combined effects of alcohol, cannabis, and tobacco were compared in this study. A total of 35 rats were assigned randomly into seven groups A-G: animals in A were administered distilled water. Animals in B-G were either administered alcohol orally (30 ml 40% alcohol) or exposed to smoke from ignited tobacco (exposure to smoke from 0.7 g tobacco for 5 min) or cannabis (exposure to smoke from 0.7 g tobacco and cannabis for 5 min): B (orally administered alcohol), C (exposed to the smoke from tobacco), D (exposed to smoke from cannabis), E (treated with alcohol and exposed to smoke from tobacco), F (treated with alcohol and exposed to smoke from cannabis), G (treated with alcohol and exposed to smokes from tobacco and cannabis). Assays were carried on the testicular homogenate after a 14-day treatment. There was a significant increase in activity of alkaline phosphatase ( P  ≤ 0.05), concentrations of cholesterol, glutathione reductase, and malondialdehyde in treated rats by the co-administration of alcohol with cannabis and tobacco compared with the control group. The combined treatment also caused degeneration and morphological distortions of testicular cells. The biochemical and histoarchitectural change was due to oxidative damage attributable to the synergistic effects. The high binding energy of tetrahydrocannabinol ligand to prostate acid phosphatase may be a prediction that the ligand can have an inhibitory effect on the function of enzymes in the prostate., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

This study investigated the effect of ketogenic diet on monosodium glutamate (MSG)-induced testicular dysfunction. Forty-six male rats (180 ± 40 g) were grouped into two groups (23 rats each); control group and MSG-induced group (4 mg/kg bw) for 28 days. At the 29th day, 5 rats from both group were sacrificed to establish testicular dysfunction. The remaining animals from the control group was further divided into three sub-groups and treated for 42 days; untreated group, ketogenic diet only and curcumin only as the standard drug (150 mg/kg bw). In the pre-treatment, the administration of MSG resulted in a significant (p < 0.05) decrease in the testis-body weight ratio, alkaline phosphatase (ALP), acetylcholine esterase (AChE), cholesterol, triglycerides (TG), nitric oxide (NO), glycogen, protein and antioxidant enzymes in the testis. In the post treatment, the MSG only group significantly reduced testicular cholesterol, catalase (CAT) and NO. In contrast, MSG + ketogenic diet group showed a significant increase in levels of rat testicular acid phosphatase (ACP), ALP, cholesterol, HMG-CoA, TG, malondialdehyde (MDA), reduced glutathione (GSH) and NO. The ketogenic diet showed a significant increase (p < 0.05) in the levels of NO, ALP, cholesterol, HMG CoA reductase and (TG). In addition, significant increases in levels of rat testicular ACP, ALP, HMG-CoA, (CAT), SOD and GSH were recorded for MSG + Curcumin group. Taken together, the findings support the prospects of ketogenic diet to enhance the testicular function in rats., Competing Interests: Declaration of Competing Interest The authors have no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Toxoplasmosis is a common parasitic disease caused by Toxoplasma gondii. Limitations of available treatments motivate the search for better therapies for toxoplasmosis. In this study, we synthesized a series of new imidazole derivatives: bis-imidazoles (compounds 1-8), phenyl-substituted 1H-imidazoles (compounds 9-19), and thiopene-imidazoles (compounds 20-26). All these compounds were assessed for in vitro potential to restrict the growth of T. gondii. To explore the structure-activity relationships, molecular analyses and bioactivity prediction studies were performed using a standard molecular model. The in vitro results, in combination with the predictive model, revealed that the imidazole derivatives have excellent selectivity activity against T. gondii versus the host cells. Of the 26 compounds screened, five imidazole derivatives (compounds 10, 11, 18, 20, and 21) shared a specific structural moiety and exhibited significantly high selectivity (> 1176 to > 27,666) towards the parasite versus the host cells. These imidazole derivatives are potential candidates for further studies. We show evidence that supports the antiparasitic action of the imidazole derivatives. The findings are promising in that they reinforce the prospects of imidazole derivatives as alternative and effective antiparasitic therapy as well as providing evidence for a probable biological mechanism.

Reproductive dysfunction is often characterized by malfunction of the reproductive tissues, which may lead to disruption of the synergistic rhythm that should bring about a progression of sexual events and the conception of new life. This may therefore result in the sexual dysfunction and infertility that can be seen in couples having prolonged biological difficulty in reproducing their offspring after having unrestricted sexual intercourse for at least twelve months. Several factors have been implicated in the cause and progression of reproductive dysfunction, including poor nutrition, drug side effects, disease states, and toxicant ingestion. A well-known food additive that has been found to be potent at initiating reproductive anomalies in males is monosodium glutamate (MSG). This regular flavor enhancer is widely used as a taste enhancer in several diets. The different mechanisms by which it may induce reproductive dysfunctions include spermatogenic alteration resulting in a low sperm count, high sperm abnormality, reduced live sperm and decreased sperm pH, oxidative damage (increased lipid peroxidation and reduced antioxidant enzyme activities), histological alteration (blood hemorrhage, distorted germ and Sertoli cells), as well as gonadotropin imbalance (reduced testosterone, luteinizing hormone, and follicle-stimulating hormone concentrations). Therefore, this review discusses various established mechanisms through which MSG may induce reproductive dysfunction and the treatment strategies to ameliorate its toxic effects., Competing Interests: The authors declare no conflict of interest.

Toxoplasmosis, which affects more than a billion people worldwide, is a common parasitic infection caused by the obligate intracellular parasite, Toxoplasma gondii . Current treatment strategies have several limitations, including unwanted side effects and poor efficacy. Therefore, newer therapies are needed for toxoplasmosis. Drug repurposing and screening of a vast array of natural and/or synthetic compounds is a viable option for antiparasitic drug discovery. In this study, we screened 62 compounds comprising natural products (NPs) and FDA-approved (FDA) drugs, to identify the hit compounds that suppress the growth of T. gondii . To determine the parasite inhibitory potential of the compounds, host mammalian cells were infected with a transgenic T. gondii strain, and the viability of the parasite was evaluated by luminescence. Of the 62 compounds, tubericidin, sulfuretin, peruvoside, resveratrol, narasin and diacetoxyscirpenol of the natural product isolates, as well as bortezonib, 10-Hydroxycamtothecin, mebendazole, niflumic acid, clindamycin HCl, mecamylamine, chloroquine, mitomycin C, fenbendazole, daunorubicin, atropine, and cerivastatin of FDA molecules were identified as "hits" with ≥ 40 percent anti-parasite action. Additionally, mitomycin C, radicicol, naringenin, gitoxigenin, menadione, botulin, genistin, homobutein, and gelsemin HCl of the natural product isolates, as well as lomofungin, cyclocytidine, prazosin HCl, cerivastatin, camptothecin, flufenamic acid, atropine, daunorubicin, and fenbendazole of the FDA compounds exhibited cytotoxic activity, reducing the host viability by ≥ 30 percent. Our findings not only support the prospects of drug repurposing, but also indicate that screening a vast array of molecules may provide viable sources of alternative therapies for parasitic infection.