ABSTRACT
In recent years, the possibility of increasing the low cryoresistance of sturgeon sperm by using antioxidants in basic cryoprotective media has been studied. The goal of this work was to review the current literature on impact of the cryoprotectors, well-known antioxidants and new multifunctional compounds on the activity indicators and fertilizing capability of sperm, as well as on biomarkers of cryostress. A special attention is given to the radical scavenging activity of studied compounds in relation to the highly reactive oxygen species, to prevent and negate oxidative stress damage of sturgeon sperm. Also, new trends for future research through the application of novel polyfunctional antioxidants to sturgeon sperm cryopreservation were indicated.
Subject(s)
Cryopreservation , Spermatozoa , Antioxidants/chemistry , Humans , MaleABSTRACT
The antioxidant and cryoprotective efficiencies of a 3,5-di-tert-butyl-4-hydroxyphenyl)methylenediphosphonic acid (MDPA) differ significantly for sperm cells of various species of sturgeon fish (Russian sturgeon, beluga and Stellate sturgeon). The ability of phosphorus-containing phenol MDPA to decrease the level of lipid peroxidation of sperm, beneficial effect on the activity indicators of the sperm of native sturgeon and of the defrosted one after deep freezing as well as on the fertility of sperm cells was shown.
Subject(s)
Cryopreservation , Semen Preservation , Animals , Cryopreservation/methods , Cryoprotective Agents/pharmacology , Humans , Male , Phenol , Phenols/pharmacology , Phosphorus , Russia , Sperm Motility , SpermatozoaABSTRACT
Metal-based drugs are gaining momentum as a rapidly developing area of medicinal inorganic chemistry. Among gold pharmaceuticals, auranofin is a well known antirheumatic drug. The efficacy of gold-organic complexes largely depends on their pro-oxidant properties since auranofin targets the redox enzyme thioredoxin reductase (TrxR). However, an uncontrollable oxygen burst may be harmful for healthy cells; therefore, the search for chemical modifications to attenuate oxidation-related general toxicity of gold containing anti-inflammatory drugs is justified. In this study, we demonstrate that the incorporation of a specific antioxidant phenol fragment can counterbalance the pro-oxidative potential of the Au containing complex molecule. The electrochemical studies of AuPPh3SR (1, R= 3,5-di-tert-butyl-4-hydroxyphenyl) and its precursors AuPPh3Cl (2) and RSH (3) showed that complex 1 and phenol 3 efficiently scavenged the radicals (as detected by cyclic voltammetry) whereas 2 had no effect. Compound 1 inhibited TrxR in vitro with IC50 0.57 ± 0.15 µM, a value one order of magnitude bigger than the potency reported for auranofin. Compound 1 (5 mg kg-1 daily gavage for 14 days) caused a decrease in ex vivo spontaneous and ascorbate-induced lipid peroxidation in the homogenates of rat lung, heart muscle, spleen, liver, kidneys, testicles and brain as assessed by the thiobarbituric acid reactive substances. Importantly, in animals fed with 1, no discernible general toxicity was registered suggesting that this compound is well tolerated. Our results provide evidence for an efficient synthetic route to obtain gold containing anti-inflammatory drug candidates with balanced pro/anti-oxidative properties.
Subject(s)
Antioxidants/pharmacology , Auranofin/pharmacology , Lipid Peroxidation , Oxidants/pharmacology , Oxidative Stress , Phenols/chemistry , Reactive Oxygen Species/metabolism , Animals , Antioxidants/chemistry , Antirheumatic Agents/chemistry , Antirheumatic Agents/pharmacology , Auranofin/chemistry , Free Radical Scavengers/chemistry , Free Radical Scavengers/pharmacology , Male , Oxidants/chemistry , Oxidation-Reduction , RatsABSTRACT
Heterocyclic derivatives of butylated hydroxytoluene (BHT) were studied as cryoprotectants of the basic media for cryopreservation of the Russian sturgeon sperm. Rates of lipid peroxidation of sturgeon sperm before and after cryopreservation were reduced in the presence of the studied compounds, exceeding the effects of BHT and water-soluble analogue of vitamin E, trolox. The most efficient antioxidant has the effective concentration of 0.1 mM. Novel antioxidant agents as cryomedium supplements not only reduced the level of lipid peroxidation, but also enhanced the translational motility of the sperm of the Russian sturgeon after defrosting.
Subject(s)
Antioxidants/pharmacology , Butylated Hydroxytoluene/pharmacology , Cryopreservation/methods , Cryoprotective Agents/pharmacology , Fishes/physiology , Spermatozoa/drug effects , Animals , Butylated Hydroxytoluene/metabolism , Chromans/pharmacology , Lipid Peroxidation/drug effects , Male , Phenols/metabolismABSTRACT
A cryoprotective effect of an addition of a new synthetic antioxidant - a representative of phosphorus-containing sterically hindered phenols is presented. The efficiency of the compound was shown to exceed the effect of lipid-soluble antioxidants butylated hydroxytoluene (BHT) and trolox in the conditions of cryopreservation of beluga sperm in the presence of the modified Stein's medium. It was shown that the level of carbonyl oxidation by-products, which can react with thiobarbituric acid (TBARS), in beluga sperm was inversely proportional to the motility time of sperm cells. The fertility of beluga sperm increased 2 times upon the addition of phosphorus-containing phenol to a modified Stein's medium. The prospects of the new antioxidant application to improve cryoresistance of beluga sperm in the conditions of cryopreservation for its efficient protection from the peroxidation processes are discussed.
Subject(s)
Antioxidants/metabolism , Cryopreservation/veterinary , Cryoprotective Agents/metabolism , Fishes/physiology , Phenols/metabolism , Semen Preservation/veterinary , Spermatozoa/cytology , Animals , Antioxidants/chemistry , Beluga Whale , Butylated Hydroxytoluene/metabolism , Chromans/metabolism , Cryopreservation/methods , Cryoprotective Agents/chemistry , Female , Fertilization , Lipid Peroxidation/drug effects , Male , Phenols/chemistry , Phosphorus/chemistry , Phosphorus/metabolism , Semen Preservation/methods , Sperm Motility/drug effects , Spermatozoa/drug effects , Spermatozoa/metabolismABSTRACT
A series of organotin complexes with Sn-S bonds of formulae Me2Sn(SR)2 (1); Et2Sn(SR)2 (2); (n-Bu)2Sn(SR)2 (3); Ph2Sn(SR)2 (4); R2Sn(SR)2 (5); Me3SnSR (6); Ph3SnSR (7) (R = 3,5-di-tert-butyl-4-hydroxyphenyl) were synthesized and characterized by elemental analysis, (1)H, (13)C NMR, and IR. The crystal structures of compounds 1, 4, 5, and 7 were determined by X-ray diffraction analysis. The tetrahedral geometry around the Sn center in the monocrystals of 1, 4, 5, and 7 was confirmed by X-ray crystallography. The high radical scavenging activity of the complexes was confirmed spectrophotometrically in a DPPH-test. The binding affinity of 1-7 and the starting R2SnCl2 (8) towards tubulin through their interaction with SH groups of proteins was studied. It was found that the hindered organotin complexes could interact with the colchicine site of tubulin, which makes them promising antimitotic drugs. Compounds 1-8 were tested for their in vitro cytotoxicity against human breast (MCF-7) and human cervix (HeLa) adenocarcinoma cells. Complexes 1-8 were also tested against normal human fetal lung fibroblast cells (MRC-5). Complexes 2-4 and 8 exhibit significantly lower cytostatic activity against the normal MRC-5 cell line compared to the tumor cell lines MCF-7 and HeLa used. A high activity against both cell lines 250 nM (MCF-7) and 160 nM (HeLa) was determined for the triphenyltin complex 7 while the introduction of hindered phenol groups decreases the cytotoxicity of the complexes against normal cells.
