ABSTRACT
Oxidative stress contributes importantly to the aetiology of male infertility, impairing sperm function. The protective effect of antioxidants on seminal parameters has been established, and the antioxidant penicillamine has shown beneficial effects; however, its protective effect on human spermatozoa exposed to oxidative stress has not been reported. The objective of this work was to evaluate the effect of penicillamine on human spermatozoa exposed in vitro to oxidative stress. First, the effect of penicillamine on spermatozoa from normozoospermic donors was evaluated. Then, the effect of penicillamine on spermatozoa exposed to oxidative stress induced separately by ionomycin and hydrogen peroxide (H2 O2 ) was analysed. An untreated control and a control treated only with the oxidative stress inducer were included. Reactive oxygen species (ROS) levels, viability, mitochondrial membrane potential (MMP) and motility were analysed. The results showed that penicillamine, added to the incubation medium, decreased the ROS levels induced by ionomycin and H2 O2 , and this effect was associated with better preservation of MMP, motility, and ATP levels. These results highlight the potential advantages of penicillamine supplementation of sperm culture medium, especially for semen samples with high ROS levels and also in circumstances where laboratory handling can cause an increase in ROS production.
Subject(s)
Antioxidants/pharmacology , Infertility, Male/therapy , Oxidative Stress/drug effects , Penicillamine/pharmacology , Semen Preservation/methods , Culture Media/pharmacology , Humans , Hydrogen Peroxide/toxicity , Infertility, Male/pathology , Ionomycin/toxicity , Male , Membrane Potential, Mitochondrial/drug effects , Reactive Oxygen Species/metabolism , Reproductive Techniques, Assisted , Sperm Motility/drug effects , Spermatozoa/drug effects , Spermatozoa/pathologyABSTRACT
Our aim was to investigate the antioxidant potential of lycopene in different experimental liver models: in vitro, to evaluate the influence of lycopene on reactive oxygen species (ROS) production mediated by the PKC pathway and in vivo, to evaluate the protective effects of lycopene in an experimental model of hepatotoxicity. The in vitro study assessed the lycopene antioxidant potential by the quantification of ROS production in SK-Hep-1 cells unstimulated or stimulated by an activator of the PKC pathway. The role of NADPH oxidase was evaluated by measuring its inhibition potential using an inhibitor of this enzyme. In the in vivo study, male C57BL/6 mice received lycopene (10 or 100 mg/kg by oral gavage) and 1 h later, acetaminophen (APAP) (500 mg/kg) was administrated. Lycopene decreased ROS production in SK-Hep-1 cells through inhibition of NADPH oxidase, brought about in the PKC pathway. Lycopene improved hepatotoxicity acting as an antioxidant, reduced GSSG and regulated tGSH and CAT levels, reduced oxidative damage primarily by decreasing protein carbonylation, promoted the downregulation of MMP-2 and reduced areas of necrosis improving the general appearance of the lesion in C57BL/6 mice. Lycopene is a natural compound that was able to inhibit the production of ROS in vitro and mitigate the damage caused by APAP overdose in vivo.
Subject(s)
Acetaminophen/toxicity , Antioxidants/pharmacology , Carotenoids/pharmacology , Chemical and Drug Induced Liver Injury/prevention & control , Liver/drug effects , Animals , Antioxidants/therapeutic use , Carotenoids/therapeutic use , Catalase/metabolism , Cell Line , Cell Survival/drug effects , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/pathology , Glutathione/metabolism , Glutathione Peroxidase/metabolism , Glutathione Reductase/metabolism , Ionomycin/toxicity , Liver/enzymology , Liver/metabolism , Lycopene , Male , Matrix Metalloproteinase 2/metabolism , Mice , Mice, Inbred C57BL , NADPH Oxidases/metabolism , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolismABSTRACT
Two new methymycin derivatives, 3'-demethylmethymycin (1) and 3'-demethyldeoxymethymycin (2), together with seven known ones (3-9), were obtained from the strain Streptomyces venezuelae ATCC 15439. Their structures were determined on the basis of IR, MS, 1D and 2D NMR data. In addition, the inhibitory effects of all the compounds on human T cell proliferation mediated by PMA/ionomycin were evaluated. The data suggested for the first time that methymycin derivatives have potential anti-inflammatory activity.