Plasma amino acids in four models of experimental liver injury in rats

Abstract

We studied the plasma amino acid profiles in four models of hepatic injury in rats. In partially hepatectomized rats (65% of liver was removed) we observed significant increase of aromatic amino acids (AAA; i.e. tyrosine and phenylalanine), taurine, aspartate, threonine, serine, asparagine, methionine, ornithine and histidine. Branched-chain amino acids (BCAA; i.e. valine, leucine and isoleucine) concentrations were unchanged. In ischemic and carbon tetrachloride acute liver damage we observed extreme elevation of most of amino acids (BCAA included) and very low concentration of arginine. In carbon tetrachloride induced liver cirrhosis we observed increased levels of AAA, aspartate, asparagine, methionine, ornithine and histidine and decrease of BCAA, threonine and cystine. BCAA/AAA ratio decreased significantly in partially hepatectomized and cirrhotic rats and was unchanged in ischemic and acute carbon tetrachloride liver damage. We conclude that a high increase of most of amino acids is characteristic of fulminant hepatic necrosis; decreased BCAA/AAA ratio is characteristic of liver cirrhosis; and decrease of BCAA/AAA ratio may not be used as an indicator of the severity of hepatic parenchymal damage.

Profile of Plasma Amino Acid Levels in Rats Exposed to Acute Hypoxic Hypoxia

“…Marked increases in AST, ALT and LDH as markers of hepatic injury indicate that serious and acute liver damage occurred. These observations suggest that a large amount of the arginase contained in the liver is likely to have leaked out into the circulating blood and led to the conversion of arginine to ornithine [10,11]. Exposure to hypoxia, however, resulted in no change in the levels of these marker enzymes compared to normoxic controls, suggesting that hepatic injury had not occurred under the hypoxic conditions used.…”

“…In the current study, acute hepatic injury induced by a single administration of CCl 4 resulted in an elevation in both the levels of BCAAs and AAAs and significant decrease in the Fischer ratio. Holecek et al [10] reported that the Fischer ratio remained unaffected by acute liver damage, in contrast to the reported response to liver cirrhosis. The reason for difference between their and our results may be attributed to the severity of liver damage, as judged by amino acid levels and activities of marker enzymes in liver injury.…”

Branched-chain amino acids and ammonia metabolism in liver disease: Therapeutic implications

“…Acute injury or the decompensation of a previously wellcompensated liver disease result in a marked increase in aminoacidemia, including the BCAA, due to the leak of amino acids from dying hepatocytes into the circulation [40,41,[65][66][67]. On the other hand, in the recovery phase after acute liver injury in rats we observed a decrease in a group of amino acids in blood plasma, including the BCAA, below the control values [67].…”

“…The decrease of plasma BCAA levels is a hallmark of liver cirrhosis [40,41] and it might be suggested that the favorable effects of BCAA supplementation on hepatic encephalopathy, protein balance, glucose tolerance, immunity, and liver functions reported in a number of studies result mostly (if not entirely) from corrections of disadvantages resulting from their deficiency. Therefore, theoretically, BCAA supplementation might be of benefit particularly in patients with low BCAA levels.…”

Evidence of a vicious cycle in glutamine synthesis and breakdown in pathogenesis of hepatic encephalopathy–therapeutic perspectives

“…However, a serious problem in many trials evaluating the effectiveness of BCAA is the lack of information about alterations in aminoacidemia. An increase in BCAA levels has been observed in acute injury or in the case of acute decompensation of liver disease (Rosen et al 1977; Hehir et al 1985; Holecek et al 1996a; Holecek et al 1999). …”