Inactivation of kupffer cells by gadolinium chloride protects murine liver from radiation-induced apoptosis.
OBJECTIVE
To determine whether the inhibition of Kupffer cells before radiotherapy (RT) would protect hepatocytes from radiation-induced apoptosis.


METHODS
A single 30-Gy fraction was administered to the upper abdomen of Sprague-Dawley rats. The Kupffer cell inhibitor gadolinium chloride (GdCl3; 10 mg/kg body weight) was intravenously injected 24 h before RT. The rats were divided into four groups: group 1, sham RT plus saline (control group); group 2, sham RT plus GdCl3; group 3, RT plus saline; and group 4, RT plus GdCl3. Liver tissue was collected for measurement of apoptotic cytokine expression and evaluation of radiation-induced liver toxicity by analysis of liver enzyme activities, hepatocyte micronucleus formation, apoptosis, and histologic staining.


RESULTS
The expression of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha was significantly attenuated in group 4 compared with group 3 at 2, 6, 24, and 48 h after injection (p <0.05). At early points after RT, the rats in group 4 exhibited significantly lower levels of liver enzyme activity, apoptotic response, and hepatocyte micronucleus formation compared with those in group 3.


CONCLUSIONS
Selective inactivation of Kupffer cells with GdCl3 reduced radiation-induced cytokine production and protected the liver against acute radiation-induced damage.
Du
Shi-Suo
SS
Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Qiang
Min
M
Zeng
Zhao-Chong
ZC
Ke
Ai-Wu
AW
Ji
Yuan
Y
Zhang
Zheng-Yu
ZY
Zeng
Hai-Ying
HY
Liu
Zhongshan
Z
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D017209:Apoptosis; D001219:Aspartate Aminotransferases / Q000097:blood; D015153:Blotting, Western; D005682:Gadolinium / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007728:Kupffer Cells / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D015162:Micronucleus Tests; D011833:Radiation Injuries, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011879:Radiotherapy Dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000098902:CD163 Antigen
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D053583:Interleukin-1beta; D015850:Interleukin-6; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; D005682:Gadolinium; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C038958:gadolinium chloride