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Study of Reproductive Toxicity of the Liposomal Photosensitizer Lipophthalocyan
Objective Study of embryotoxicity, teratogenicity and reproductive toxicity of the new drug Lipophtalocyan in rats.
Material and Methods Studies were conducted on 210 non-inbred female rats and 105 non-inbred male rats. The drug was administered daily via i. v. injection for 48 days (males) and for 15 days (females) in 2 total doses corresponding to the therapeutic dose (TD) for mice when converted to rats and 10 TD.
Results and Conclusion When mating with intact female rats, no changes in sexual behavior were observed, but the index of the ability to fertilize and conceive decreased when compared to the values of the control group by 35–40% (TD index=60%) and by 75–80% (10 TD index=20%). The index of the ability to fertilize and conceive differed from the values of the control group by 90% (TD index=5%) and by 15% (10 TD index=80%). There were no differences in the indicator of embryotoxicity and teratogenicity in intact and drug-treated female rats, compared with the control group. Lipophtalocyan has a negative effect on the male and female reproductive function in rats and has an embryotoxic effect according to the index of the ability to fertilize and conceive, as well as the indices of preimplantation and post-implantation fetal death. The drug does not have a teratogenic effect, neither it affects the physical development of offspring or the rate of maturation of sensory-motor reflexes during feeding.
Received: 25 March 2021
Accepted: 21 June 2021
29 July 2021 (online)
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Georg Thieme Verlag KG
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- 1 Meerovich IG, Sanarova EV, Meerovich GA. et al. Near-infrared photosensitizers based on nanostructured forms of phthalocyanine derivatives. Russ J General Chem 2015; 85: 280-288 DOI: 10.1134/S1070363215010430.
- 2 Sanarova EV, Lantsova AV, Polozkova AP. et al. Effectiveness of liposomal system of delivery of hydrophobic antineoplastic thiosens photosensitizer. Nanotechnologies in Russ 2015; 10: 492-500 DOI: 10.1134/S1995078015030143.
- 3 Meerovich GA, Borisova LM, Bud’Ko AP. et al. Study of level and selectivity of liposomal form of photosensitiser hydroxyaluminium tetra-3-phenylthiophthalocyanine accumulation on transplantable mice tumor models at different ways of transplantation. Russ J Biother 2017; 16: 74-79. DOI: 10.17650/1726-9784-2017-16-4-74-79.
- 4 Budko AP, Deichman ZG, Meerovich GA. et al. Study of pharmacokinetics of liposomal photosensitiser based on hydroxyaluminium tetra-3-phenylthiophthalocyanine on mice. Biomedical Photonics 2018; 4: 16-22. DOI: 10.24931/2413-9432-2018-7-4-16-22.
- 5 Meerovich I, Nichols MG, Dash AK. Low-intensity light-induced paclitaxel release from lipid-based nano-delivery systems. J Drug Targeting 2019; 27: 971-983. DOI: 10.1080/1061186X.2019.1571066.
- 6 Koshkaryev A, Thekkedath R, Pagano C. et al. Intracellular Targeting of Lysosomes by Liposomes Modified with Octadecyl-Rhodamine B. J Drug Targeting 2011; 19: 606-614 DOI: 10.3109/1061186X.2010.550921.
- 7 Smol’nikova NM, Chirkova EM, Golovanova IV. et al. Guidelines for the preclinical study of the reproductive toxicity of pharmacological agents. Vedomosti Farmakologicheskogo Komiteta 1998; 1: 13-20
- 8 Smolnikova NM, Lyubimov BI, Durnev AD. et al. Methodical recommendations for study of reproductive toxicity of pharmacological substances. In: Khabriev RU (Ed).Guidance on the experimental (preclinical) study of new pharmacological substances. Moscow: Medicine; 2005: 87-100
- 9 Durnev AD, Smolnikova NM, Skosyreva AM. et al. Methodical recommendations for the study of reproductive toxicity of drugs. In: Mironov AN (ed). Preclinical Drug Research Guide, part 1. Moscow: Grif & K; 2012: 80-93
- 10 Bol'shakov OP, Neznanov NG, Babakhanyan RV. Didactic and ethical aspects of research on biomodels and laboratory animals. Kachestvennaya klinicheskaya praktika 2002; 1: 58-61 https://www.clinvest.ru/jour/article/view/249#tab1
- 11 Freireich EJ, Gehan EA, Rall DP. et al. Quantitative comparison of toxicity of anticancer agents in mouse, rat, hamster, dog, monkey, and man. Cancer Chemother Rep 1966; 50: 219-244