Aim: 

The aim of the present study was to investigate the effect of aging and ovariectomy on various physiological parameters related to inflammation and oxidative stress in livers obtained from old female rats and the influence of chronic exogenous administration of estrogens, phytoestrogens, growth hormone and melatonin on these.

Methods: 

Sixty-one 22 month old Wistar female rats were used. Intact animals were divided into three groups and treated for 10 weeks with GH, melatonin or saline, and 40 ovariectomized animals were divided into five groups and treated for the same time with GH, melatonin, estrogens, phytoestrogens or saline. A group of 2 month old female rats was used as young control. Protein expression of iNOS, HO-1, BVR, IL-6, TNFa, and IL-1b were determined by western blot analysis. The levels of NO_x, LPO, TNFa, IL-1b, IL-6, IL-10 and HO, FMO, GST activity were determined in different fractions of the liver.

Results: 

Ovariectomy and aging induced a significant decrease in activity of GST and FMO in the microsomal fraction as compared to young controls and treatment with GH, melatonin, Eos and Phyt were able to revert these changes. The activity of microsomal HO and HO-1 protein expression were reduced after melatonin and Eos treatment. Hormonal administration to the ovariectomized groups decreased NO_x, LPO levels and pro-inflammatory cytokines as compared with untreated rats. Significant rise in IL-10 and reductions in the iNOS, IL-6, TNFa and IL-1b proteins expression were also found. Treatment with Eos and melatonin to ovariectomized females showed significantly up-regulated values of the protein expression of BVR in liver.

Conclusion: 

Oxidative stress and inflammation induced during aging in the liver are more marked in castrated than in intact old females. Administration of the different hormonal replacement therapies inhibit the induction of pro-inflammatory cytokines and iNOS, increased activity of drug-metabolizing enzymes and have therapeutic potential in the prevention of liver injury.

This work was supported by grants: RETICEF RD 06/0013 (FIS) and SAF 2007, 66878-C02-01. Dr. Kireev Roman was supported by Nutricia Research Foundation, International Training Fellowship (2007-T4).