Dovhal H. V., Dovhal M. A., Romanenko O. A., Zharikov M. Yu., Romanenko K. L.


About the author:

Dovhal H. V., Dovhal M. A., Romanenko O. A., Zharikov M. Yu., Romanenko K. L.



Type of article:

Scentific article


The aim of the study was to determine the expression of the spectrum of immunohistochemical markers in the liver in the early postnatal period of rats after exposure to lead acetate during pregnancy and under correction. From the first day of pregnancy, female Wistar rats were exposed to lead acetate in an aqueous solution at a dose of 20 mg/kg per os daily; in the correction group, the same dose of lead acetate and lycopene (500 mg/kg) was administered. The liver of rat pups underwent the immunohistochemical analysis on the 1st, 3rd and 7th day of life; the control was the liver of intact rat pups. In the group after exposure to lead acetate, changes in rat liver parenchyma within 1-7 days included dystrophy, particulary the granulations and vacuolation of the cytoplasm. Interstitial edema and moderate interstitial infiltration by lymphoid cells were also observed. Pathomorphological changes increased during the 1st week. The decrease of AE1/AE3 expression was corresponded to the common degenerative changes in the liver parenchyma. Some liver parenchyma nuclei were positive for the caspase-3 marker, and within 1-7 days, most of stromal nucleus cells were caspase-3-positive. No changes in WT1 expression were observed. MMP-1 and MMP-9 expression was significantly suppressed in the cells of the interlobular stroma. Endothelial cells showed weak immunostaining of eNOS in most vessels at day 1st. Subsequent observations showed the stable inhibition of the synthesis of this enzyme. The highest number of αSMA-positive interstitial cells was observed in the peripheral parts of organ, which underwent severe fibrotic changes. Hepatocyte cytoplasm was weakly positive for VEGF, its expression was no longer heterogeneous. There were areas of liver that had no staining at all, they also demonstrated the most pronounced dystrophic changes. Stromal cells, as in the control group, showed a clear expression of VEGF. This pattern persisted for 1-7 days postnatal period. Hepatocytes with caspase-3 positive nuclei were more abundant at day 1 compared to control. The number of such nuclei increased during the first postnatal week. In the group after exposure to lead acetate and lycopene correction, AE1/AE3 expression was suppressed less than in the non-correction group, but we did not observe areas with clear staining as normal. In the cytoplasm of hepatocytes, the distribution of this marker was not uniform. As in the non-correction group, WT1 expression did not differ from normal. Expression of eNOS decreased within 1-7 days of life, compared to the control group, in small caliber vessels, in most cases of interlobular, there was a suppression of immunostaning. The number of cells positive for αSMA was slightly lower than in the intact liver, but their distribution pattern was similar to normal. Stromal cells showed the high level of VEGF expression, especially in areas with fibrotic changes. The expression of VEGF in the cytoplasm of hepatocytes was similar to the group after lead acetate treatment without correction. Caspase-3-positive hepatocytes were more abundant in the peripheral parts of the organ, however, they were generally less in number than in the group after exposure to lead acetate. The expression of MMP-1 and MMP-9 was at the same level as in the group after treatment with the toxicant only. We conclude that the expression of immunohistochemical markers in the liver of rat during 1-7 days of life showed the different susceptibility to lead acetate after maternal treatment during the whole pregnancy, and the corrective potential of lycopene. The most vulnerable was the expression of VEGF, caspase-3, AE1/AE3, MMP-1 and MMP-9; lycopene showed a slight corrective ability for their synthesis, but it was more beneficial for the eNOS expression


liver, postnatal period, rats, lead acetate, immunohistochemical markers.


  1. Aleksiichuk VD, Sokurenko LM, Omelchuk ST. Osoblyvosti vplyvu nanochastok sulfidu ta nitratu svyntsu na orhanizm eksperymentalnykh tvaryn u rizni periody doslidzhennia ta metody korektsii yikh nehatyvnoi dii. Svit medytsyny ta biolohii. 2015;54(4):97-100. [in Ukrainian].
  2. Vylegzhanina TA. Vliyanie acetata svinca na razvitie pecheni krys. Original’nye nauchnye publikacii. 2015;44-8. [in Russian].
  3. Dovhal HV, Dovhal MA, Romanenko OA. Pathomorphology of fetal and mature liver under the lead intoxication and after the correction: the review of experimental data. Pathologia. 2019;1(45):139-44. DOI: 10.14739/2310-1237. 2019.1.166497
  4. Dovhal HV, Dovhal MA, Shevchenko IV. Porushennia morfohenezu sertsia shchuriv pid vplyvom atsetatu svyntsiu ta za umov korektsii. Visnyk problem biolohii i medytsyny. 2018;4(147):271-6. DOI: 10.29254/2077-4214-2018-4-2-147-271-276 [in Ukrainian].
  5. Liu CM, Ma JQ, Sun YZ. Puerarin protects the rat liver against oxidative stress-mediated DNA damage and apoptosis induced by lead. Exp Toxicol Pathol. 2012;64(6):575-82. DOI: 10.1016/j.etp.2010.11.016
  6. Dovhal HV, Dovhal MA, Romanenko OA. The expression of immunohistochemical markers in the fetal liver after maternal exposure of lead acetate and under the correction. Science Rewiew. 2017;7:17-9. Available from: pw0567.pdf
  7. Gargouri M, Ben Saad H, Ben Amara I, Magné C, El Feki A. Spirulina exhibits hepatoprotective effects against lead induced oxidative injury in newborn rats. Cell Mol Biol. 2016;62(10):85-93. DOI:10.14715/cmb/2016.62.10.14
  8. Gargouri M, Magné C, Ben Amara I, Ben Saad H, El Feki A. Dandelion-enriched diet of mothers alleviates lead-induced damages in liver of newborn rats. Cell Mol Biol. 2017;63(2):67-75. DOI: 10.14715/cmb/2017.63.2.10

Publication of the article:

«Bulletin of problems biology and medicine» Issue 1 (155), 2020 year, 297-301 pages, index UDK 611.36: 611.136.41:611.013]-092.9