Nitric oxide-mediated effects of L-ornithine-L-aspartate in acute toxic liver injury

Abstract

This study was aimed to investigate nitric oxide-dependent mechanisms of L-ornithine-L-aspartate (LOLA) action in acute toxic liver injury in rats. Acute hepatitis was induced in Wistar rats using 50% oil solution of tetrachloromethane (CCl4) intragastrically (2 g/kg) twice in a 24 hour interval. Intraperitoneal treatment with LOLA (200 mg/kg) was started 6 hours after the second CCl4 administration and maintained for 3 consecutive days. L-Nω-Nitroarginine Methyl Ester (L-NAME) was used intraperitoneally (10 mg/kg). In CCl4-induced hepatitis, LOLA restores the structure of hepatocytes and prevents aminotransferases, alkaline phosphatase and gamma-glutamyl transferase elevation. It decreases total bilirubin concentration but does not affect increased cholesterol level. LOLA augments urea concentration, total protein level in blood and liver as well as serum and liver content of nitrite anions. LOLA enhances activity of catalase, glutathione S-transferase, manganese superoxide dismutase, increases reduced glutathione level and total antioxidant capacity and decreases thiobarbituric acid reactive substances level. The concomitant use of L-NAME inhibits the action of LOLA to enhance nitrite anions synthesis both in serum and liver, to delay the recovery of hepatocytes, to counteract LOLA effect against blood total protein reduction, to prevent the decline in aminotransferases, alkaline phosphatase,, gamma-glutamyl transferase and glutathione S-transferase activity and to reduce catalase activity and reduced glutathione level. Therefore, in CCl4-induced hepatitis, LOLA effectively prevents cytolysis and cholestasis, improves liver metabolism and protects against oxidative stress. Partially, these changes occur in nitric oxide-mediated mechanism since the use of L-NAME declines most of LOLA effects.

Oxidative Mechanisms Underlying Brain Cell Damage in Rats Under Changes in Duration of the Lightdark Cycles

“…Відомо, що метаболізм L-аргініну відбувається за NOсинтазним шляхом, де утворюється оксид азоту, та аргіназним. Орнітиндекарбоксилаза приймає участь в аргіназному шляху перетворення Lаргініну: каталізує лімітуючу стадію біосинтезу поліамінів -декарбоксилювання L-орнітину, проміжної сполуки циклу сечовини, з утворенням путресцину [16]. Підвищення активності ОДК свідчить про активацію саме аргіназного шляху метаболізму L-аргініну у тканинах головного мозку щурів другої групи.…”