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BrdU does not induce hepatocellular damage in experimental Wistar rats.

Abril Alondra Barrientos-Bonilla1, Paola Belem Pensado-Guevara2, Abraham Puga-Olguín3

  • 1Centro de Investigaciones Biomédicas, Universidad Veracruzana, Xalapa, Veracruz, Mexico.

Acta Histochemica
|November 28, 2023
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Summary

Bromodeoxyuridine (BrdU) administration did not cause liver damage in rats undergoing partial hepatectomy. While BrdU did not induce apoptosis, elevated liver enzymes were observed, indicating potential systemic effects.

Keywords:
Adult ratsCell deathHepatocellular damageIntraperitonealLiver function

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Area of Science:

  • Biomedical research
  • Toxicology
  • Cell biology

Background:

  • Bromodeoxyuridine (BrdU) is a thymidine analog crucial for cell proliferation and neurogenesis studies.
  • Repeated administration of BrdU may impact liver function, necessitating investigation.
  • Partial hepatectomy (PHx) models are used to study liver regeneration and drug effects.

Purpose of the Study:

  • To assess the systemic and hepatocellular effects of multiple Bromodeoxyuridine (BrdU) administrations in a rat partial hepatectomy (PHx) model.
  • To evaluate potential liver function profile changes induced by BrdU.
  • To determine if BrdU causes hepatocellular damage or apoptosis post-PHx.

Main Methods:

  • Male Wistar rats underwent 30% partial hepatectomy (PHx) and received BrdU (50 mg/Kg) via intraperitoneal injection at multiple time points post-surgery.
  • Groups included control, sham, PHx without BrdU (PHx/BrdU(-)), and PHx with BrdU (PHx/BrdU(+)).
  • Liver function markers (ALT, AST, LDH, AP, bilirubin, proteins, albumin), histopathology (hematoxylin-eosin), and apoptosis (caspase-3) were analyzed on day 16.

Main Results:

  • Bromodeoxyuridine (BrdU) did not induce significant hepatocellular damage or apoptosis in male rats post-PHx.
  • Multiple BrdU administrations did not cause a significant decrease in body weight.
  • Elevated serum levels of alanine transferase (ALT) and lactate dehydrogenase (LDH) were observed.

Conclusions:

  • Bromodeoxyuridine (BrdU) administration, even multiple times, does not appear to cause direct hepatocellular damage in this rat model.
  • The observed increase in ALT and LDH suggests potential systemic effects or transient liver stress rather than direct toxicity.
  • Further research is warranted to fully elucidate the systemic impact of BrdU in regenerative models.