Supplementation with branched-chain amino acids attenuates hepatic apoptosis in rats with chronic liver disease.
Branched-chain amino acids (BCAA) can function as pharmacologic nutrients for patients with decompensated cirrhosis. However, the effects of BCAA at the early stage of chronic liver disease are not clear. We hypothesized that early BCAA supplementation would attenuate the progression of chronic liver disease. The present study examined the effects of BCAA supplementation on the progression of chronic liver disease in rats caused by injected carbon tetrachloride (CCl₄). Sprague-Dawley rats were fed with a casein diet (control group) or the same diet supplemented with BCAA (BCAA group) for 11 weeks, and all rats were repeatedly injected with CCl₄. Food intake did not significantly differ between control and BCAA groups during the experimental period. Plasma alanine aminotransferase activities gradually increased during the experimental period in both groups but peaked later in the BCAA group. Liver fibrosis was more evident in the control group. Levels of connective tissue growth factor messenger RNA were significantly lower in the livers of rats in the BCAA group than in the control group. Terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick end labeling assays found considerably more hepatic apoptosis in the control group. Liver cytosolic cytochrome c levels and expression of the proapoptotic Bax protein in the mitochondrial fraction were significantly lower in the BCAA group than in the control group. These results suggest that supplementation with BCAA delays the progression of chronic liver disease caused by CCl₄ in rats by attenuating hepatic apoptosis.
Department of Nutrition Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, 1-5 Shimogamo-hangi-cho, Sakyo, Kyoto 606-8522, Japan. kuwahata@kpu.ac.jp
Masashi
M
Kuwahata
Hiroyo
H
Kubota
Hiroaki
H
Kanouchi
Shunsuke
S
Ito
Aki
A
Ogawa
Yukiko
Y
Kobayashi
Yasuhiro
Y
Kido
D000597:Amino Acids, Branched-Chain / Q000008:administration & dosage* / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002251:Carbon Tetrachloride / Q000633:toxicity; D002364:Caseins / Q000008:administration & dosage; D002908:Chronic Disease; D019587:Dietary Supplements; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017423:Sequence Analysis, RNA; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
D000597:Amino Acids, Branched-Chain; C494828:Bax protein, rat; D002364:Caseins; D051028:bcl-2-Associated X Protein; D002251:Carbon Tetrachloride