PROTECTIVE ROLE OF ERYTHROPOIETIN PRETREATED MESENCHYMAL STEM CELLS IN ANTI-TUBERCULOUS DRUGS-INDUCED LIVER TOXICITY IN ALBINO RATS
Ahmed Wafiq Elzainy
Anatomy department, Faculty of Medicine, Cairo University and Qassim University
Background: long term use of anti-tuberculous (ATT) drugs is considered an important problem that needs to be solved due to their toxic effects on many organs including the liver. Aim of work: The current study was designed to evaluate the possible effect of bone marrow derived mesenchymal stem cells (BM-MSCs) pretreated with Erythropoietin (EPO) in liver tissue protection and regeneration against the toxic effects of the anti-tuberculous drugs. Materials and Methods: Twenty-four adult male Sprague Dawley albino rats with an average weight of 200-250 g were divided into three equal groups (eight rats in each group): group I (control group), group II (ATT treated group) given INH, RMP, PZA and EMB in a single daily dose 100, 300, 700 and 155 mg/kg body weight respectively, suspended in 1% starch gel for twenty-eight days, group III (ATT and EPO pretreated BM-MSCs group) received one systemic injection (through the caudal vein) of MSCs (1 x 106) diluted in 0.5 ml of PBS at day one of the experiment. Sections of the liver were examined for histological and immunofluorescent studies and histomorphometrical analysis. Results: Marked hepatocyte damage was detected in the ATT treated group in the form of loss of their normal laminar pattern with dilatation and congestion of the portal veins and thickening of their walls, in addition to inflammatory cellular infiltration. Necrosis of some hepatocytes in the form of nuclear pyknosis, karyolisis and karyorrhexis were seen with dissolution of the cytoplasm and macrovesicular steatosis in the liver tissue. Significant increase of the levels of pro-inflammatory factors TNF-α, IL-1ß and NF-ҡß and the apoptotic factor TP53 was observed. Significant increase in the area percent of collagen fibers and decrease in PAS reaction were detected. EPO pretreated BM-MSCs group revealed the presence of PKH26 labeled stem cells within the liver tissue denoting their homing to the site of injured tissue. Their specimens showed nearly normal microscopic features of the hepatocytes. Decrease in the levels of TNF-α, IL-1ß, NF-ҡß and TP53 with minimal increase in the collagen fibers and increase PAS reaction reflecting the protective role of the mesenchymal stem cells pretreated with EPO of the liver tissue against ATT toxicity. Conclusion: EPO pretreated BM-MSCs ameliorated ATT-induced hepatic toxicity and could preserve normal histological liver structure.