Molecular and cellular mechanisms of acute cytotoxic liver damage as potential biological targets for magnesium-containing cell-protective drug

Abstract

Introduction. Many anti-tumor drugs have a high potential for toxic damage to liver cells, which makes it necessary to identify molecular mechanisms of the development of the negative impact of drugs on the liver and to develop effective methods for preventing and correcting this adverse effect. Materials and methods. The study was performed on 30 nonlinear white rats of both sexes weighing 180–220 g, divided into 3 equal groups (n = 10 in each): intact control, control with liver pathology and experimental group of rats receiving the test substance LBK-527 at a dose of 100 mg/kg/day intragastrically one hour before the administration of a hepatoxic cytarabine. In the animals of the latter two groups, acute drug-induced hepatitis was simulated by intravenous administration of 2 g/m2 cytarabine in physiological saline for 5 days. Liver pathomorphology was studied on specimens stained with hematoxylin and eosin, Sudan III and by Van Gieson; a semi-quantitative method for assessing the depth of inflammatory and dystrophic organ damage was used. In the blood plasma, the activity of ASAT, ALAT, GGTP, and APF was determined. Tissue concentrations of TNF-alpha, IL-10 and HGF were determined by quantitative ELISA. Expression of Bcl-2 and Ki-67 was studied by immunohistochemistry. The proliferation index was calculated. Results and discussion. Daily administration of LBK-527 for 5 days restrains the depth of cytarabine-induced pathomorphological changes in the liver, reduces the prevalence of the dystrophic and inflammatory process, increases the anti-inflammatory and regenerative potential of the hepatic parenchyma, inhibits the programmed death of hepatocytes and reduces the activity of cytolytic and cholestatic syndromes. Conclusion. Magnesium-containing cell-protective substance LBK-527 protects liver from cytarabine-induced injury.

Protective effect of l-carnitine on oxidative stress in the liver of acute hepatotoxicity male ratsafter cytarabine chemotherapy

“…Twenty-four (24) male white albino rat were used in this experiment and their ages between (12)(13)(14) weeks and they were (260-300) gm per body weight and the animals were placed in good condition in special plastic cages and provided the animals with the appropriate conditions in terms of temperature around (30 ±5 C°) and ventilation and the light system was 12 hrs. per day.…”

“…L-carnitine may provide cell membranes protection against oxidative stress, given its pivotal role in fatty acid oxidation and energy metabolism (9). L-carnitine has the potential to protect these cellular events in several manners including decreasing the production of reactive oxygen species at different points and maintaining mitochondrial functions (14).…”