TY  - JOUR
AU  - Nikolić-Kokić, Aleksandra
AU  - Tatalović, Nikola
AU  - Brkljačić, Jelena
AU  - Mijović, Milica
AU  - Nestorović, Vojkan
AU  - Mijušković, Ana
AU  - Oreščanin-Dušić, Zorana
AU  - Vidonja Uzelac, Teodora
AU  - Nikolić, Milan
AU  - Spasić, Snežana
AU  - Blagojević, Duško
AU  - Miljević, Čedo
PY  - 2022
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5669
AB  - Sexual dysfunction, as a noticeable adverse effect of atypical antipsychotic drugs (APDs) for the treatment of schizophrenia, has not been investigated in detail. A study was undertaken to investigate whether 28-day long treatment with clozapine, ziprasidone or sertindole (using a recommended daily dose for atypical antipsychotic therapy), induced histopathological changes both in rat testicles and prostate, changed the activity of the antioxidant defence system and altered blood testosterone and prolactin. Clozapine, ziprasidone and sertindole induced histopathological changes in rat testicular tissue, which could be attributed to a disturbed testicular antioxidant defence system in addition to an altered prolactin to testosterone ratio. None of the APD treatments induced histopathological changes in prostate. Our results demonstrate that APDs have the capacity to change both redox and endocrinological balance. One or both outcomes could underline testicular degeneration and disturbed spermatogenesis.
PB  - MDPI
T2  - International Journal of Molecular Sciences
T1  - Antipsychotic Drug-Mediated Adverse Effects on Rat Testicles May Be Caused by Altered Redox and Hormonal Homeostasis
VL  - 23
SP  - 13698
DO  - 10.3390/ijms232213698
ER  - 

@article{
author = "Nikolić-Kokić, Aleksandra and Tatalović, Nikola and Brkljačić, Jelena and Mijović, Milica and Nestorović, Vojkan and Mijušković, Ana and Oreščanin-Dušić, Zorana and Vidonja Uzelac, Teodora and Nikolić, Milan and Spasić, Snežana and Blagojević, Duško and Miljević, Čedo",
year = "2022",
abstract = "Sexual dysfunction, as a noticeable adverse effect of atypical antipsychotic drugs (APDs) for the treatment of schizophrenia, has not been investigated in detail. A study was undertaken to investigate whether 28-day long treatment with clozapine, ziprasidone or sertindole (using a recommended daily dose for atypical antipsychotic therapy), induced histopathological changes both in rat testicles and prostate, changed the activity of the antioxidant defence system and altered blood testosterone and prolactin. Clozapine, ziprasidone and sertindole induced histopathological changes in rat testicular tissue, which could be attributed to a disturbed testicular antioxidant defence system in addition to an altered prolactin to testosterone ratio. None of the APD treatments induced histopathological changes in prostate. Our results demonstrate that APDs have the capacity to change both redox and endocrinological balance. One or both outcomes could underline testicular degeneration and disturbed spermatogenesis.",
publisher = "MDPI",
journal = "International Journal of Molecular Sciences",
title = "Antipsychotic Drug-Mediated Adverse Effects on Rat Testicles May Be Caused by Altered Redox and Hormonal Homeostasis",
volume = "23",
pages = "13698",
doi = "10.3390/ijms232213698"
}

Nikolić-Kokić, A., Tatalović, N., Brkljačić, J., Mijović, M., Nestorović, V., Mijušković, A., Oreščanin-Dušić, Z., Vidonja Uzelac, T., Nikolić, M., Spasić, S., Blagojević, D.,& Miljević, Č.. (2022). Antipsychotic Drug-Mediated Adverse Effects on Rat Testicles May Be Caused by Altered Redox and Hormonal Homeostasis. in International Journal of Molecular Sciences
MDPI., 23, 13698.
https://doi.org/10.3390/ijms232213698

Nikolić-Kokić A, Tatalović N, Brkljačić J, Mijović M, Nestorović V, Mijušković A, Oreščanin-Dušić Z, Vidonja Uzelac T, Nikolić M, Spasić S, Blagojević D, Miljević Č. Antipsychotic Drug-Mediated Adverse Effects on Rat Testicles May Be Caused by Altered Redox and Hormonal Homeostasis. in International Journal of Molecular Sciences. 2022;23:13698.
doi:10.3390/ijms232213698 .

Nikolić-Kokić, Aleksandra, Tatalović, Nikola, Brkljačić, Jelena, Mijović, Milica, Nestorović, Vojkan, Mijušković, Ana, Oreščanin-Dušić, Zorana, Vidonja Uzelac, Teodora, Nikolić, Milan, Spasić, Snežana, Blagojević, Duško, Miljević, Čedo, "Antipsychotic Drug-Mediated Adverse Effects on Rat Testicles May Be Caused by Altered Redox and Hormonal Homeostasis" in International Journal of Molecular Sciences, 23 (2022):13698,
https://doi.org/10.3390/ijms232213698 . .

TY  - JOUR
AU  - Stanković, Dalibor
AU  - Ristić, Slavica M.
AU  - Vukadinović, Aleksandar
AU  - Mirković, Marija D.
AU  - Vladimirov, Sandra S.
AU  - Milanović, Zorana
AU  - Radović, Magdalena
AU  - Mijović, Milica
AU  - Stanković, Dalibor
AU  - Sabo, Tibor
AU  - Vranješ-Đurić, Sanja
AU  - Janković, Drina
PY  - 2019
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2894
AB  - It was reported that novel O,O′-diethyl-(S, S)-ethylenediamine-N,N′-di-2-(3-cyclohexyl) propanoate dihydrochloride (DE-EDCP) displayed in vitro antiproliferative activity on several human and mouse cancer cell lines, which was comparable to that of the prototypical anticancer drug cisplatin. In order to reveal its toxicity profile, acute and repeated-dose toxicity studies were performed in Naval Medical Research Institute (NMRI) Han mice. The intravenous LD 50 values of DE-EDCP were found to be 95.3 and 101.3 mg/kg body weight in female and male mice, respectively. In the subacute toxicity study, DE-EDCP was administered intravenously at the doses of 15, 25, and 40 mg/kg/day for a period of 28 days. There were no adverse effects on general condition, growth, feed and water consumption, and hematological parameters. There was a significant increase in urea and alanine aminotransferase in female mice and aspartate aminotransferase and alkaline phosphatase in both genders in 40 mg/kg/day dose-treated group. The histopathological changes confined to the liver and kidney, but in other organs were not found. Satellite group revealed that changes in the kidney and liver were less pronounced, suggesting their reversibility. Interactions with DNA could also be of importance for understanding DE-EDCP toxic side effects. Hyperchromic effect obtained with ultraviolet–visible, suggested electrostatic interactions between DE-EDCP and calf thymus DNA. The toxicity testing of DE-EDCP was conducted to predict human outcomes.
PB  - SAGE PUBLICATIONS LTD
T2  - Human and Experimental Toxicology
T1  - Toxicity study of DE-EDCP as a potential drug for cancer therapy: Toxicity profile of DE-EDCP
VL  - 38
IS  - 4
SP  - 466
EP  - 481
DO  - 10.1177/0960327118819047
ER  - 

@article{
author = "Stanković, Dalibor and Ristić, Slavica M. and Vukadinović, Aleksandar and Mirković, Marija D. and Vladimirov, Sandra S. and Milanović, Zorana and Radović, Magdalena and Mijović, Milica and Stanković, Dalibor and Sabo, Tibor and Vranješ-Đurić, Sanja and Janković, Drina",
year = "2019",
abstract = "It was reported that novel O,O′-diethyl-(S, S)-ethylenediamine-N,N′-di-2-(3-cyclohexyl) propanoate dihydrochloride (DE-EDCP) displayed in vitro antiproliferative activity on several human and mouse cancer cell lines, which was comparable to that of the prototypical anticancer drug cisplatin. In order to reveal its toxicity profile, acute and repeated-dose toxicity studies were performed in Naval Medical Research Institute (NMRI) Han mice. The intravenous LD 50 values of DE-EDCP were found to be 95.3 and 101.3 mg/kg body weight in female and male mice, respectively. In the subacute toxicity study, DE-EDCP was administered intravenously at the doses of 15, 25, and 40 mg/kg/day for a period of 28 days. There were no adverse effects on general condition, growth, feed and water consumption, and hematological parameters. There was a significant increase in urea and alanine aminotransferase in female mice and aspartate aminotransferase and alkaline phosphatase in both genders in 40 mg/kg/day dose-treated group. The histopathological changes confined to the liver and kidney, but in other organs were not found. Satellite group revealed that changes in the kidney and liver were less pronounced, suggesting their reversibility. Interactions with DNA could also be of importance for understanding DE-EDCP toxic side effects. Hyperchromic effect obtained with ultraviolet–visible, suggested electrostatic interactions between DE-EDCP and calf thymus DNA. The toxicity testing of DE-EDCP was conducted to predict human outcomes.",
publisher = "SAGE PUBLICATIONS LTD",
journal = "Human and Experimental Toxicology",
title = "Toxicity study of DE-EDCP as a potential drug for cancer therapy: Toxicity profile of DE-EDCP",
volume = "38",
number = "4",
pages = "466-481",
doi = "10.1177/0960327118819047"
}

Stanković, D., Ristić, S. M., Vukadinović, A., Mirković, M. D., Vladimirov, S. S., Milanović, Z., Radović, M., Mijović, M., Stanković, D., Sabo, T., Vranješ-Đurić, S.,& Janković, D.. (2019). Toxicity study of DE-EDCP as a potential drug for cancer therapy: Toxicity profile of DE-EDCP. in Human and Experimental Toxicology
SAGE PUBLICATIONS LTD., 38(4), 466-481.
https://doi.org/10.1177/0960327118819047

Stanković D, Ristić SM, Vukadinović A, Mirković MD, Vladimirov SS, Milanović Z, Radović M, Mijović M, Stanković D, Sabo T, Vranješ-Đurić S, Janković D. Toxicity study of DE-EDCP as a potential drug for cancer therapy: Toxicity profile of DE-EDCP. in Human and Experimental Toxicology. 2019;38(4):466-481.
doi:10.1177/0960327118819047 .

Stanković, Dalibor, Ristić, Slavica M., Vukadinović, Aleksandar, Mirković, Marija D., Vladimirov, Sandra S., Milanović, Zorana, Radović, Magdalena, Mijović, Milica, Stanković, Dalibor, Sabo, Tibor, Vranješ-Đurić, Sanja, Janković, Drina, "Toxicity study of DE-EDCP as a potential drug for cancer therapy: Toxicity profile of DE-EDCP" in Human and Experimental Toxicology, 38, no. 4 (2019):466-481,
https://doi.org/10.1177/0960327118819047 . .

TY  - JOUR
AU  - Nikolić-Kokić, Aleksandra
AU  - Tatalović, Nikola
AU  - Nestorov, Jelena
AU  - Mijović, Milica
AU  - Mijušković, Ana
AU  - Miler, Marko
AU  - Oreščanin-Dušić, Zorana
AU  - Nikolić, Milan
AU  - Milošević, Verica
AU  - Blagojević, Duško P.
AU  - Spasic, Mihajlo
AU  - Miljević, Čedo
PY  - 2018
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2206
AB  - Atypical antipsychotics produce severe side effects including myocarditis that may be attributed to oxidative stress. The aim of this study was to investigate the influence of clozapine, ziprasidone, and sertindole on rat heart morphology and determine whether redox imbalane plays a role in development of histopathological changes. Adult 3-month-old male Wistar rats were treated with recommended daily dose for selected drugs. After 4week treatment histopathological analysis of the heart was performed and expression and activity of antioxidant enzymes determined. All examined drugs induced histopathological changes that were characterized as toxic myocarditis. Degenerative changes in cardiomyocytes were accompanied by lymphocytic infiltration as well as pericardial histopathological alterations in all treated groups. The least prominent changes were observed in sertindole-treated animals, and most severe with clozapine. Clozapine increased superoxide dismutase 1 (SOD1) activity while ziprasidone reduced glutathione reductase (GR) activity. Sertindole exerted no marked effect on antioxidant enzyme function in the heart even though myocardial degeneration was noted. In conclusion, treatment with clozapine or ziprasidone induced pathophysiological alterations in rat heart, which appeared to be associated disturbances in antioxidant capacity.Abbreviation: AAP, Atypical antipsychotics; ROS, reactive oxygen species; SOD1, Copper-zinc superoxide dismutase; SOD2, Manganese superoxide dismutase; CAT, Catalase; GPx, Glutathione peroxidase; GR, Glutathione reductase; H&E, hematoxylin and eosin stain; TNF- , tumor necrosis factor alpha.
PB  - Taylor & Francis Inc, Philadelphia
T2  - Journal of Toxicology and Environmental Health. Part A
T1  - Clozapine, ziprasidone, and sertindole-induced morphological changes in the rat heart and their relationship to antioxidant enzymes function
VL  - 81
IS  - 17
SP  - 844
EP  - 853
DO  - 10.1080/15287394.2018.1495587
ER  - 

@article{
author = "Nikolić-Kokić, Aleksandra and Tatalović, Nikola and Nestorov, Jelena and Mijović, Milica and Mijušković, Ana and Miler, Marko and Oreščanin-Dušić, Zorana and Nikolić, Milan and Milošević, Verica and Blagojević, Duško P. and Spasic, Mihajlo and Miljević, Čedo",
year = "2018",
abstract = "Atypical antipsychotics produce severe side effects including myocarditis that may be attributed to oxidative stress. The aim of this study was to investigate the influence of clozapine, ziprasidone, and sertindole on rat heart morphology and determine whether redox imbalane plays a role in development of histopathological changes. Adult 3-month-old male Wistar rats were treated with recommended daily dose for selected drugs. After 4week treatment histopathological analysis of the heart was performed and expression and activity of antioxidant enzymes determined. All examined drugs induced histopathological changes that were characterized as toxic myocarditis. Degenerative changes in cardiomyocytes were accompanied by lymphocytic infiltration as well as pericardial histopathological alterations in all treated groups. The least prominent changes were observed in sertindole-treated animals, and most severe with clozapine. Clozapine increased superoxide dismutase 1 (SOD1) activity while ziprasidone reduced glutathione reductase (GR) activity. Sertindole exerted no marked effect on antioxidant enzyme function in the heart even though myocardial degeneration was noted. In conclusion, treatment with clozapine or ziprasidone induced pathophysiological alterations in rat heart, which appeared to be associated disturbances in antioxidant capacity.Abbreviation: AAP, Atypical antipsychotics; ROS, reactive oxygen species; SOD1, Copper-zinc superoxide dismutase; SOD2, Manganese superoxide dismutase; CAT, Catalase; GPx, Glutathione peroxidase; GR, Glutathione reductase; H&E, hematoxylin and eosin stain; TNF- , tumor necrosis factor alpha.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Journal of Toxicology and Environmental Health. Part A",
title = "Clozapine, ziprasidone, and sertindole-induced morphological changes in the rat heart and their relationship to antioxidant enzymes function",
volume = "81",
number = "17",
pages = "844-853",
doi = "10.1080/15287394.2018.1495587"
}

Nikolić-Kokić, A., Tatalović, N., Nestorov, J., Mijović, M., Mijušković, A., Miler, M., Oreščanin-Dušić, Z., Nikolić, M., Milošević, V., Blagojević, D. P., Spasic, M.,& Miljević, Č.. (2018). Clozapine, ziprasidone, and sertindole-induced morphological changes in the rat heart and their relationship to antioxidant enzymes function. in Journal of Toxicology and Environmental Health. Part A
Taylor & Francis Inc, Philadelphia., 81(17), 844-853.
https://doi.org/10.1080/15287394.2018.1495587

Nikolić-Kokić A, Tatalović N, Nestorov J, Mijović M, Mijušković A, Miler M, Oreščanin-Dušić Z, Nikolić M, Milošević V, Blagojević DP, Spasic M, Miljević Č. Clozapine, ziprasidone, and sertindole-induced morphological changes in the rat heart and their relationship to antioxidant enzymes function. in Journal of Toxicology and Environmental Health. Part A. 2018;81(17):844-853.
doi:10.1080/15287394.2018.1495587 .

Nikolić-Kokić, Aleksandra, Tatalović, Nikola, Nestorov, Jelena, Mijović, Milica, Mijušković, Ana, Miler, Marko, Oreščanin-Dušić, Zorana, Nikolić, Milan, Milošević, Verica, Blagojević, Duško P., Spasic, Mihajlo, Miljević, Čedo, "Clozapine, ziprasidone, and sertindole-induced morphological changes in the rat heart and their relationship to antioxidant enzymes function" in Journal of Toxicology and Environmental Health. Part A, 81, no. 17 (2018):844-853,
https://doi.org/10.1080/15287394.2018.1495587 . .