In patients with abdominal region
cancers, ionizing radiation (IR)-induced long-term liver injury is a major limiting factor in the use of
radiotherapy. Previously, the major mitochondrial deacetylase,
sirtuin 3 (
SIRT3), has been implicated to play an important role in the development of acute liver injury after total body irradiation but no studies to date have examined the role of
SIRT3 in liver's chronic response to radiation. In the current study, ten-month-old
Sirt3-/- and
Sirt3+/+ male mice received 24 Gy radiation targeted to liver. Six months after exposure, irradiated
Sirt3-/- mice livers demonstrated histopathological elevations in inflammatory infiltration, the loss of mature bile ducts and higher DNA damage (TUNEL) as well as
protein oxidation (3-nitrotyrosine). In addition, increased expression of inflammatory
chemokines (IL-6, IL-1β, TGF-β) and fibrotic factors (
Procollagen 1, α-SMA) were also measured in
Sirt3-/- mice following 24 Gy IR. The alterations measured in enzymatic activities of
catalase,
glutathione peroxidase, and
glutathione reductase in the livers of irradiated
Sirt3-/- mice also implied that
hydrogen peroxide and
hydroperoxide sensitive signaling cascades in the absence of
SIRT3 might contribute to the IR-induced long-term liver injury.