Alterações metabólicas e enzimáticas na regeneração hepática em ratos alimentados com dietas suplementar de L-Glutamina e Alfa-Cetoglutarato

Abstract

Studies have shown that partial hepatectomia (HP) with removal of two thirds of the organ, in rodents, is followed by growth of remnant liver. In eukaryotic cells the enzyme malate dehydrogenase, from Krebs cycle, can be found in the cytoplasm (cytoplasmic malate dehydrogenase (MDH1) and in the mitochondrial matrix mitochondrial malate dehydrogenase (MDH2). Ammonia, a chemical compound that is toxic to animals, is produced in the course of metabolism. The liver actively participates in the mechanism of detoxification of ammonia. Two enzymes are involved in the disposal of excess ammonia in the cytosol: the glutamate dehydrogenase and glutamine synthetase which reduce α-ketoglutarate (AKG) to glutamate and glutamate to glutamine (GLN), respectively. Considering the effects of AKG and GLN in the liver of rodents, this study aims at assessing the metabolic enzyme changes that take place in regenerating livers after HP in rats treated with these amino acids. Anesthetized rats (Ketamine 50mg/mL + Xilazine 2% -1:0,5 mL) were submitted to HP and treated with calcium caseinate (CCA), L-glutamine (GLN) or ornithine alpha ketoglutarate (OKG) solutions administered by gavage, according to weight of each animal (0, 5gKg). One hundred and eight rats were distributed in 6 groups (n=18) and named according to the treatment used: G-1= Laparotomy (LAP) + CCA; G-2-HP+CCA; G-3 = LAP + GLN; G-4 HP + GLN; G-5 = LAP +ACG; G-6 = HP + ACG. Each group was redistributed into 3 subgroups. Blood and liver samples were collected on the 3rd, 7th and 14th postoperative days for quantification of metabolites (glucose, ketone bodies, lactate, pyruvate and ATP) and enzymes (MDH1 and MDH2). There was an increase of glycemia in 3rd day both in rats subjected to LAP and treated with ACG (G-5) as well as those submitted to HP and treated with GLN (G-3). There was significant reduction in expression of MDH1 enzyme in the liver in the 3rd and 14th day in rats subjected to LAP and treated with ACG and GLN (G-5 and G-3) compared to the control G-1 as well as in the expression of the enzyme MDH2 in 3rd day in the liver of G-6 and G-2 rats. Moreover no changes occurred in the expression of MDH2 in Group G-4 in relation to G-2. It is concluded that the surgical trauma in animals subjected to LAP or HP and treated with ACG or GLN induces increased glycemia in post-operative stage. ACG or GLN promotes reduction in expression of MDH1 enzyme in the liver of rats subjected to surgical trauma in 3rd and 14 days post surgery. ACG promotes reduction in the expression of MDH2 in the liver of rats undergoing HP or LAP only on the 3rd and 14 days post surgery, respectively. GLN given to HP rats does not alter the expression of MDH2 in the liver during the first 14 days post surgery.