Effects of Total Parenteral Nutrition with Nucleoside and Nucleotide Mixture on D‐Galactosamine‐Induced Liver Injury in Rats

Abstract

The effect of a nucleoside-nucleotide mixture on liver injury of rats induced by D-galactosamine was studied by examining changes in function and histopathology of the liver. Animals with liver damage received total parenteral nutrition with glucose and amino acids supplemented with a nucleoside-nucleotide mixture containing inosine, cytidine, GMP, uridine and thymidine, or with uridine which inhibits galactosamine injury, or with liver cell extract containing flavin adenine dinucleotide and nucleic acid derivatives. As control, animals with liver damage received total parenteral nutrition with glucose and amino acids only. The serum GOT and GPT concentrations were significantly lower in the group supplemented with nucleoside-nucleotide mixture than those in other groups. A large dose (1.2 g/kg) of uridine inhibited liver injury, but a lower dose (0.14 g/kg) did not have any effect, whereas nucleoside-nucleotide mixture containing the same amount of uridine inhibited the injury. Liver cell extract also did not improve liver function. Thus infusion of a physiological and balanced mixture of nucleosides or nucleotides may improve liver function in rats with liver injury.

Gastroprotective effects of oral nucleotide administration

“…12 Similarly, an NT mixture was effective when administered intravenously to rats with D-galactosamine induced liver injury. 13 In addition, small pilot human studies have shown that polydeoxyriboNT, given as eye drops, increased corneal epithelial regeneration 14 and when given by combined intramuscular and subcutaneous route, increased the rate of healing of autologous skin grafts. 15 In conclusion, our studies have shown that NTs, commercially available as over the counter ''health food'' supplements for licensing purposes, possesses biological activity when assessed using several models of gut integrity and repair.…”

The Role of Nucleotides in the Immune and Gastrointestinal Systems

“…Over the course of 5 weeks, hepatic cholesterol and lipid phosphorous were significantly higher, and liver weight and glycogen were lower in weanling mice on a nucleotide‐free diet compared with those on nucleotide‐containing diets 83 . Nucleoside‐nucleotide mixtures added to amino acids and glucose and administered parenterally demonstrated favorable effects on nitrogen metabolism and liver function in rats with liver injury induced by D‐galactosamine, a condition histologically comparable to viral hepatitis in humans 84 . Dietary nucleotides also demonstrated beneficial effects in rats with liver cirrhosis in which nucleotide supplementation showed extensive structural repair to cellular damage within 2 weeks 85 .…”

The role of dietary nucleotides in single-stomached animals

“…Several studies with rodents and cats are available focusing on potential effects of supplemental dietary nucleotides and/or nucleosides on blood parameters (14) , on hepatic blood flow (61) and on liver morphology (62) . Novak et al (14) reported increased hepatic cholesterol and lipid P concentration as well as 4·0 11·3 12·8 6·8 4·3 3·0 2·19 CMP 1·5 7·1 7·1 3·5 2·3 0·9 0·98 GMP 5·4 14·7 14·0 10·2 6·0 7·1 1·41 IMP 1·1 1·8 2·6 1·4 0·9 0·4 0·38 UMP 555·6 305·6 263·1 144·0 122·8 104·0 27·05 AMP, adenosine 5 0 -monophosphate; CMP, cytosine 5 0 -monophosphate; GMP, guanosine 5 0 -monophosphate; IMP, inosine 5 0 -monophosphate; UMP, uridine 5 0 -monophosphate.…”

“…Ogoshi et al (62) showed that parenteral nutrition based on a balanced mixture of nucleosides and nucleotides at a physiological level may improve hepatic function in rats and promote earlier restoration of N balance following liver injury. These findings were confirmed in experiments with hepatectomised rabbits which showed an enhanced mitochondrial phosphorylative activity in the remnant liver, when fed a nucleoside-nucleotide mixture (64) .…”