Naoyuki Matsumura

Lipid peroxidation and lysosomal enzymes in D-galactosamine hepatitis and its protection by vitamin E

SummaryRole of Iipid peroxidation on lysosomal instability in liver tissue was investigated in an experimental model of D-galactosamine hepatitis in rats fed on vitamin E (V.E) deficient diet.Administration of D-galactisamine to V.E deficient rats resulted in a sudden increase of serum glutamic oxaloacetic transaminase (sGOT), glutamic pyruvic transaminase (sGPT), lipid peroxide value, as well asβ glucuronidase and acid phosphatase activity examined as markers of lysosomal enzymes, when compared with control rats fed on V.E supplemented diet.Lipid peroxide in the liver tissue also showed significant increase in V.E deficient rats. In contrast, \- glucuronidase and acid phosphatase in the liver tissue were found to decrease in V.E deficient rats by the administration of D-galactosamine, indicating that the enzymes in the lysosome were entirely released outside the liver cells as a result of cell destruction.It is concluded that the increase of lipid peroxide causes the instability of lysosomal membranes and releases various kinds of hydrolytic enzymes to lead further cell damage. V.E might act on inhibiting lipid peroxidation to stabilize lysosomal membranes.

Therapeutic Effect of a Low Dosage of Human Leukocyte Interferon on Chronic Hepatitis B Virus Infection

A low dosage of human leukocyte interferon was intramuscularly given to 47 patients with hepatitis B surface antigen (HBsAg) positive chronic active hepatitis once a week for 4 consecutive weeks (10 X 10(5), 5 X 10(5), 2 X 10(5) and 1 X 10(5) U). After treatment, a reduction of serum HBsAg was observed in 26 patients; 3 of them showed no serum HBsAg and 1 of the 3 appeared to produce antibody to HBsAg. 31 of 34 patients investigated showed a significant decrease in Dane particle-associated DNA-polymerase activity (p less than 0.001). Among 17 patients positive for hepatitis B e antigen (HBeAg), 10 of them seroconverted to anti-HBe. Serum transaminase levels also significantly improved in 34 of 38 patients (p less than 0.001). Our findings indicate that a low dosage of human leukocyte interferon such as 18 X 10(5) U, administered in progressively decreasing doses, may be effective in the treatment of chronic hepatitis B virus infection.

Effect of Low Dosage of Interferon on Natural Killer Activity in Patients with HBsAg-Positive Chronic Active Hepatitis

The effect of human leukocyte interferon (IFN) on natural killer (NK) activity in 7 patients with HBsAg-positive chronic active hepatitis was investigated. Human leukocyte IFN was intramuscularly given once a week for 4 consecutive weeks (10 X 10(5), 5 X 10(5), 2 X 10(5) and 1 X 10(5) U). 1 week after the initial injection, NK activity showed a significant rise compared with the preinjection levels (p less than 0.001) and remained elevated during the 1-month treatment, while it fell after the cessation of IFN therapy. 4 of 5 patients showed a marked decrease in Dane particle-associated DNA-polymerase activity. Serum HBeAg disappeared in 3 of 6 patients and serum transaminase levels markedly improved in all patients. Only a transient reduction in HBsAg was observed in 2 patients after the treatment period. The findings indicate that a low dosage of human leukocyte IFN such as 18 X 10(5) U, administered in decreasing doses, enhances NK activity in patients with HBsAg-positive chronic active hepatitis, and that the effect of IFN is involved in the immune mechanisms associated with natural cytotoxicity.