ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Different degrees of expression pulmonary fibrosis signs with intratracheal administration of bleomycin at different doses to male SD rats (a study aimed at helping to select the optimal bleomycin dose for modeling pulmonary fibrosis)
Provisionally accepted
Elena A. Tukhovskaya1,2*
Yulia A. Palikova2Maria S. Severyukhina2Alina M. Ismailova2
Victor Palikov2Gulsara A. Slashcheva2
Natalya Borozdina2Evgeniy S. Mikhaylov2Irina N. Kravchenko2
Vitaly Kazakov2Ekaterina N. Kazakova2Elena A. Kalabina2Ekaterina A. Rasskazova2
Igor Dyachenko2
Vladimir A. Rykov2
Olga Patsap3Alexander A. Globenko4Ekaterina A. Jain4
Andrey Kolosov4
Arkady N. Murahsev2- 1Institute of Bioorganic Chemistry (RAS), Moscow, Russia
- 2Shemyakin-Ovchinnicov Institute of Bioorganic Chemistry (Branch), Russian Academy of Sciences, Pushchino, Russia
- 3Peoples' Friendship University of Russia named after Patrice Lumumba, Miklukho-Maklaya str., 6, Moscow, 117198, Russia, Moscow, Russia
- 4Valenta Pharm JSC, Ryabinovaya street 26, building 10, Moscow, 121471, Russia, Moscow, Russia
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Pulmonary fibrosis (PF) is a life-threatening lung disease. PF develops under the influence of various damaging agents. To study new therapeutic strategies, a PF model with intratracheal administration of the bleomycin (BLM) is used. We studied the effect of different doses of BLM. The study was performed on male SD rats. BLM was administrated at doses of 0.5 mg/kg, 1.5 mg/kg, 2.5 mg/kg, 3 mg/kg and 5 mg/kg. Animals were observed for 21 days for the following parameters: overall health status, body weight gain, and external respiratory function. On the 22nd day the lung weight, cellular composition of the bronchoalveolar fluid (BALF), hydroxyproline content were determined, and degree of lungs fibrosis was histologically assessed. With an increase in the BLM dose, overall health status deteriorates, function of external respiration worsens, BALF neutrophilic infiltration increases, and increase of PF severity occurs. The least marked PF manifestations were observed after administration of BLM at a dose of 0.5 mg/kg, and the most marked after 5 mg/kg. The results demonstrate a dose-dependent BLM effect on PF severity, which gives us an idea of damaging agent different doses effect on the severity of PF.
Keywords: Pulmonary Fibrosis, Rats, Bleomycin, general health status, Dose-dependence, Lung, respiratory function, Histological assessment
Received: 10 Sep 2025; Accepted: 04 Nov 2025.
Copyright: © 2025 Tukhovskaya, Palikova, Severyukhina, Ismailova, Palikov, Slashcheva, Borozdina, Mikhaylov, Kravchenko, Kazakov, Kazakova, Kalabina, Rasskazova, Dyachenko, Rykov, Patsap, Globenko, Jain, Kolosov and Murahsev. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Elena A. Tukhovskaya, tukhovskaya@bibch.ru
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