Antibiotic treatment is superior to ursodeoxycholic acid on total parenteral nutrition associated hepatic dysfunction.
OBJECTIVE
This study aimed to investigate the apoptotic mechanisms, oxidative stress, and mechanisms of effect of antibiotics and ursodeoxycholic acid (UDCA) in total parenteral nutrition (TPN)-associated liver injury.


METHODS
Four groups of young rabbits were used in the study as follows: Group 1 (n: 7): TPN + Metronidazole (30 mg/kg IV) + Gentamicin (6 mg/kg IV); Group 2 (n: 7): TPN + UDCA (15 mg/kg per oral); Group 3 (n: 6): TPN only; and Group 4 (n: 7): Control group. After 10 days, the animals were killed and livers were removed. Hepatic apoptosis, apoptotic proteins, malondialdehyde (MDA) and myeloperoxidase (MPO) levels were studied in liver, and direct bilirubin values were assessed in the blood samples.


RESULTS
Direct bilirubin increased with TPN, and antibiotic combination, as the most effective group, significantly lowered its levels (p < 0.01). MDA values also showed significant differences in comparisons between G1 and G3 (p < 0.05) and G1-G4 (p < 0.01). An increased number of apoptotic cells was detected particularly in G2 and G3, whereas the lowest levels, other than in the control group, were found in G1. All TUNEL-positive cell number data were statistically significant except between G2 and G3(p < 0.05). Caspase-3 and Bax immunoreactivities were greatest in G2. Significant differences were shown in caspase-3 immunoreactivity between the groups (p < 0.01), except between G1 and G3 (p > 0.05). All comparisons between the groups were significant for Bax (p < 0.01). In contrast, Bcl-2 immunoreactivity was moderate and highest in G1: comparisons between G1 and the other groups demonstrated statistically significant differences (p < 0.01). Fas-L immunoreactivity was greatest in G2, and all comparisons between the groups were statistically significant (p < 0.01).


CONCLUSIONS
Metronidazole and gentamicin combination is effective on TPN-induced liver injury by the Bcl-2 anti-apoptotic pathway, total anti-apoptotic effect and by decreasing bilirubin levels. Oxidative injury in the liver increased with therapy. UDCA seems less effective on TPN-associated liver injury.
Günşar
Cüneyt
C
Department of Pediatric Surgery, Celal Bayar University Medical Faculty, 45030, Manisa, Turkey. cuneyt.gunsar@bayar.edu.tr
Vatansever
Seda
S
Var
Ahmet
A
Aygören
Reha
R
Yilmaz
Omer
O
Türköz
Elgin
E
Sencan
Aydin
A
Mir
Erol
E
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis; D001663:Bilirubin / Q000097:blood; D053148:Caspase 3 / Q000378:metabolism; D053222:Fas Ligand Protein / Q000378:metabolism; D005839:Gentamicins / Q000494:pharmacology*; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D008107:Liver Diseases / Q000188:drug therapy* / Q000209:etiology*; D008315:Malondialdehyde / Q000378:metabolism; D008795:Metronidazole / Q000494:pharmacology*; D018384:Oxidative Stress; D010289:Parenteral Nutrition, Total / Q000009:adverse effects*; D009195:Peroxidase / Q000378:metabolism; D011817:Rabbits; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D053222:Fas Ligand Protein; D005839:Gentamicins; D051028:bcl-2-Associated X Protein; D008795:Metronidazole; D008315:Malondialdehyde; D014580:Ursodeoxycholic Acid; D009195:Peroxidase; D053148:Caspase 3; D001663:Bilirubin
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