Cobalt chloride (CoCl2) induces heme oxygenase (HO-1) in adult and neonatal rats. We tested the hypothesis that upregulation of HO-1 by CoCl2 in neonatal rats was mediated by depletion of glutathione (GSH), as suggested by studies in adult rats. Rats aged 0 to 5 days were injected sc with saline or 250 μmol/kg CoCl2. After 30 or 150 min, livers were freeze-clamped and assayed for GSH. Data were analyzed by 2-way ANOVA with modified t tests. There were no interactions between day and treatment at 30 and 150 min. At 30 min, GSH levels (μmol/g liver) trended lower in the CoCl2 groups than in controls (p<.08); at 150 min the GSH levels in the CoCl2 groups were significantly lower than in controls (p<.02). At 30 and 150 min, GSH was lowest in both control and CoCl2 groups on d 1, with recovery to birth values by d 2 (*p<.02). We therefore investigated if hepatic glycogen needed for sustaining GSH by GSSG reduction might be depleted in a similar pattern. Hepatic glycogen (nmol glucose eq/g liver) was high at birth and fell significantly by d 1 (^p<0.05). Glycogen recovery is seen by d 2-3, with a slower recovery in the CoCl2 groups. Glycogen was lower at 30 and 150 min in the CoCl2 groups than in controls(p<0.01). Thus, newborns with low glycogen stores may not have full capacities to sustain hepatic GSH. The effects of CoCl2 on hepatic GSH are statistically significant; whether these changes are of sufficient magnitude to account for upregulation of HO-1 remains to be determined. The decrease in hepatic GSH on d 1 is notassociated with a major increase in basal HO activity on d 1 (Ped Res 35:78A), suggesting that CoCl2 induces HO-1 in the newborn rat by mechanisms other than simple depletion of GSH. Supported by NIH HD01124. Table
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Tom, D., Nguyen, UL. & Smith, C. EARLY EXTRAUTERINE STRESSES DEPLETE GLUTATHIONE AND GLYCOGEN IN NEWBORN RATS.401. Pediatr Res 39 (Suppl 4), 69 (1996). https://doi.org/10.1203/00006450-199604001-00421
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DOI: https://doi.org/10.1203/00006450-199604001-00421