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FeTPPS, a Peroxynitrite Decomposition Catalyst, Ameliorates Nitrosative Stress in Human Spermatozoa

ORCID
0000-0001-7358-7541
Affiliation
Center of Excellence in Translational Medicine–Scientific and Technological Bioresource Nucleus (CEMT–BIOREN), Faculty of Medicine, Universidad de La Frontera, Temuco 4810296, Chile;(P.U.);(J.B.);(K.P.);(F.Z.);(M.S.);(C.M.)
Uribe, Pamela;
Affiliation
Center of Excellence in Translational Medicine–Scientific and Technological Bioresource Nucleus (CEMT–BIOREN), Faculty of Medicine, Universidad de La Frontera, Temuco 4810296, Chile;(P.U.);(J.B.);(K.P.);(F.Z.);(M.S.);(C.M.)
Barra, Javiera;
Affiliation
Center of Excellence in Translational Medicine–Scientific and Technological Bioresource Nucleus (CEMT–BIOREN), Faculty of Medicine, Universidad de La Frontera, Temuco 4810296, Chile;(P.U.);(J.B.);(K.P.);(F.Z.);(M.S.);(C.M.)
Painen, Kevin;
ORCID
0000-0003-4840-0508
Affiliation
Center of Excellence in Translational Medicine–Scientific and Technological Bioresource Nucleus (CEMT–BIOREN), Faculty of Medicine, Universidad de La Frontera, Temuco 4810296, Chile;(P.U.);(J.B.);(K.P.);(F.Z.);(M.S.);(C.M.)
Zambrano, Fabiola;
Affiliation
Center of Excellence in Translational Medicine–Scientific and Technological Bioresource Nucleus (CEMT–BIOREN), Faculty of Medicine, Universidad de La Frontera, Temuco 4810296, Chile;(P.U.);(J.B.);(K.P.);(F.Z.);(M.S.);(C.M.)
Schulz, Mabel;
Affiliation
Center of Excellence in Translational Medicine–Scientific and Technological Bioresource Nucleus (CEMT–BIOREN), Faculty of Medicine, Universidad de La Frontera, Temuco 4810296, Chile;(P.U.);(J.B.);(K.P.);(F.Z.);(M.S.);(C.M.)
Moya, Claudia;
ORCID
0000-0002-3674-543X
Affiliation
Research Group in Reproductive Medicine, Department of Obstetrics and Gynecology, Cologne University, 50923 Köln, Germany;(V.I.);(E.I.);(P.M.)
Isachenko, Vladimir;
Affiliation
Research Group in Reproductive Medicine, Department of Obstetrics and Gynecology, Cologne University, 50923 Köln, Germany;(V.I.);(E.I.);(P.M.)
Isachenko, Evgenia;
Affiliation
Research Group in Reproductive Medicine, Department of Obstetrics and Gynecology, Cologne University, 50923 Köln, Germany;(V.I.);(E.I.);(P.M.)
Mallmann, Peter;
ORCID
0000-0003-4853-4282
Affiliation
Center of Excellence in Translational Medicine–Scientific and Technological Bioresource Nucleus (CEMT–BIOREN), Faculty of Medicine, Universidad de La Frontera, Temuco 4810296, Chile;(P.U.);(J.B.);(K.P.);(F.Z.);(M.S.);(C.M.)
Sánchez, Raúl

Excessive levels of reactive nitrogen species (RNS), such as peroxynitrite, promote nitrosative stress, which is an important cause of impaired sperm function. The metalloporphyrin FeTPPS is highly effective in catalyzing the decomposition of peroxynitrite, reducing its toxic effects in vivo and in vitro. FeTPPS has significant therapeutic potential in peroxynitrite-related diseases; however, its effects on human spermatozoa under nitrosative stress have not been described. This work aimed to evaluate the in vitro effect of FeTPPS against peroxynitrite-mediated nitrosative stress in human spermatozoa. For this purpose, spermatozoa from normozoospermic donors were exposed to 3-morpholinosydnonimine, a molecule that generates peroxynitrite. First, the FeTPPS-mediated peroxynitrite decomposition catalysis was analyzed. Then, its individual effect on sperm quality parameters was evaluated. Finally, the effect of FeTPPS on ATP levels, motility, mitochondrial membrane potential, thiol oxidation, viability, and DNA fragmentation was analyzed in spermatozoa under nitrosative stress conditions. The results showed that FeTPPS effectively catalyzes the decomposition of peroxynitrite without affecting sperm viability at concentrations up to 50 μmol/L. Furthermore, FeTPPS mitigates the deleterious effects of nitrosative stress on all sperm parameters analyzed. These results highlight the therapeutic potential of FeTPPS in reducing the negative impact of nitrosative stress in semen samples with high RNS levels.

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