A series of thirty-one hydrazones of aminoguanidine, nitroaminoguanidine, 1,3-diaminoguanidine, and (thio)semicarbazide were prepared from various aldehydes, mainly chlorobenzaldehydes, halogenated salicylaldehydes, 5-nitrofurfural, and isatin (yields of 50-99%). They were characterized by spectral methods. Primarily, they were designed and evaluated as potential broad-spectrum antimicrobial agents. The compounds were effective against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus with minimum inhibitory concentrations (MIC) from 7.8 µM, as well as Gram-negative strains with higher MIC. Antifungal evaluation against yeasts and Trichophyton mentagrophytes found MIC from 62.5 µM. We also evaluated inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The compounds inhibited both enzymes with IC50 values of 17.95-54.93 µM for AChE and ≥1.69 µM for BuChE. Based on the substitution, it is possible to modify selectivity for a particular cholinesterase as we obtained selective inhibitors of either AChE or BuChE, as well as balanced inhibitors. The compounds act via mixed-type inhibition. Their interactions with enzymes were studied by molecular docking. Cytotoxicity was assessed in HepG2 cells. The hydrazones differ in their toxicity (IC50 from 5.27 to >500 µM). Some of the derivatives represent promising hits for further development. Based on the substitution pattern, it is possible to modulate bioactivity to the desired one.

• Keywords
• acetylcholinesterase, aminoguanidine, antimicrobial activity, butyrylcholinesterase, cytotoxicity, enzyme inhibition, hydrazones, molecular docking, salicylaldehydes,
• Publication type
• Journal Article MeSH

Oxidative stress occurs when the levels of reactive oxygen species (ROS) overcome the antioxidant defenses of the organism, jeopardizing several biological functions, including reproduction. In the male reproductive system, oxidative stress not only impairs sperm fertility but also compromises offspring health and survival, inducing oxidative damage to lipids, proteins and nucleic acids. Although a clear link between oxidative stress and male fertility disorders has been demonstrated in humans and laboratory rodents, little information is available about the implications of impaired redox homeostasis in the male fertility of domestic and wild animals. Therefore, this review aims to provide an update regarding the intrinsic and extrinsic factors that are associated with oxidative stress in the male reproductive system and their impact on the reproductive performance of domestic and wild animals. The most recent strategies for palliating the detrimental effects of oxidative stress on male fertility are reviewed together with their potential economic and ecological implications in the livestock industry and biodiversity conservation.

• Keywords
• ROS, antioxidant, infertility, livestock, semen, sperm dysfunction, wildlife,
• Publication type
• Journal Article MeSH
• Review MeSH

Hydrogen sulphide (H2S) is involved in the physiology and pathophysiology of different cell types, but little is known about its role in sperm cells. Because of its reducing properties, we hypothesise that H2S protects spermatozoa against the deleterious effects of oxidative stress, a condition that is common to several male fertility disorders. This study aimed i) to determine the total antioxidant capacities of Na2S and GYY4137, which are fast- and slow-releasing H2S donors, respectively, and ii) to test whether H2S donors are able to protect spermatozoa against oxidative stress. We found that Na2S and GYY4137 show different antioxidant properties, with the total antioxidant capacity of Na2S being mostly unstable and even undetectable at 150 µM. Moreover, both H2S donors preserve sperm motility and reduce acrosome loss, although the effects were both dose and donor dependent. Within the range of concentrations tested (3-300 µM), GYY4137 showed positive effects on sperm motility, whereas Na2S was beneficial at the lowest concentration but detrimental at the highest. Our findings show that Na2S and GYY4137 have different antioxidant properties and suggest that both H2S donors might be used as in vitro therapeutic agents against oxidative stress in sperm cells, although the optimal therapeutic range differs between the compounds.

• MeSH
• Antioxidants pharmacology   MeSH
• Humans MeSH
• Morpholines pharmacology   MeSH
• Sperm Motility drug effects   MeSH
• Organothiophosphorus Compounds pharmacology   MeSH
• Oxidative Stress drug effects   MeSH
• Swine MeSH
• Spermatozoa drug effects   MeSH
• Hydrogen Sulfide metabolism   MeSH
• Sulfides pharmacology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Antioxidants MeSH
• GYY 4137 MeSH Browser
• Morpholines MeSH
• Organothiophosphorus Compounds MeSH
• sodium sulfide MeSH Browser
• Hydrogen Sulfide MeSH
• Sulfides MeSH

After being historically considered as noxious agents, nitric oxide (NO) and hydrogen sulfide (H2S) are now listed as gasotransmitters, gaseous molecules that play a key role in a variety of cellular functions. Both NO and H2S are endogenously produced, enzymatically or non-enzymatically, and interact with each other in a range of cells and tissues. In spite of the great advances achieved in recent decades in other biological systems, knowledge about H2S function and interactions with NO in sperm biology is in its infancy. Here, we aim to provide an update on the importance of these molecules in the physiology of the male gamete. Special emphasis is given to the most recent advances in the metabolism, mechanisms of action, and effects (both physiological and pathophysiological) of these gasotransmitters. This manuscript also illustrates the physiological implications of NO and H2S observed in other cell types, which might be important for sperm function. The relevance of these gasotransmitters to several signaling pathways within sperm cells highlights their potential use for the improvement and successful application of assisted reproductive technologies.

• Keywords
• gasotransmitters, hydrogen sulfide, interaction, metabolism, nitric oxide, spermatozoa,
• MeSH
• Gasotransmitters chemistry   metabolism   MeSH
• Humans MeSH
• Nitric Oxide metabolism   MeSH
• Oxidation-Reduction MeSH
• Oxidative Stress MeSH
• Reactive Nitrogen Species chemistry   metabolism   MeSH
• Sulfur chemistry   metabolism   MeSH
• Spermatozoa chemistry   enzymology   metabolism   physiology   MeSH
• Hydrogen Sulfide metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Gasotransmitters MeSH
• Nitric Oxide MeSH
• Reactive Nitrogen Species MeSH
• Sulfur MeSH
• Hydrogen Sulfide MeSH

In recent decades, an increasing number of ethnopharmacological studies have been dedicated to medicinal plants from South African fynbos. Among these plants, honeybush (Cyclopia spp.) has become a popular tea, mainly due to its healthy properties and caffeine-free status. The antioxidant, antimutagenic, and antimicrobial properties of this plant have been reported in several cell types, but its effects on reproductive function are still unknown. Here, we assessed the effects of honeybush (Cyclopia intermedia) on boar sperm parameters under induced oxidative stress (Fe2+/ascorbate) and during five days of semen storage at 17 °C without oxidative stress. In both experiments, four concentrations (200, 50, 12.5, and 3.125 µg/mL) of fermented honeybush were tested. Our results show that honeybush enhances sperm parameters, and no toxic effects were observed at any of the tested extract concentrations. Interestingly, honeybush (12.5 µg/mL) improved the sperm motility and kinetic parameters, preserved the plasma membrane integrity, and reduced the lipid peroxidation in the samples exposed to Fe2+/ascorbate (p < 0.05). In the stored samples, positive effects of honeybush on sperm parameters (motility, kinetics, acrosome, and mitochondria) were observed from 48 h until 120 h of semen storage (p < 0.05). Our results clearly show the protective effects of honeybush on sperm samples, thus promoting its use as a natural source of antioxidants for boar semen.

• Keywords
• Cyclopia intermedia, lipid peroxidation, oxidative stress, semen storage, sperm function,
• Publication type
• Journal Article MeSH