thioacetamide and isoquercitrin

The current study was conducted to evaluate the ameliorative and protective potentials of Moringea oleifera leaves ethanolic extract (MOLE) against thioacetamide (TAA) toxicity. A total of 58 male albino rats were randomly assigned into six experimental groups. G1, rats received distilled water. G2, rats were injected with a single dose of TAA (200 mg/kg BW) i.p. G3, rats were given MOLE (300 mg/kg BW) orally for 26 days. G4, rats were injected TAA as in G2 and treated with MOLE as G3. G5, rats were kept for 26 days without treatment then on day 27 injected with TAA as in G2. G6, rats were given MOLE for 26 days then on day 27 injected with TAA. Phytochemical analysis of MOLE indicated the presence of kaempferol, kaempferol malonylglucoside, kaempferol hexoside, kaempferol -3-O-glucoside, kaempferol-3-O-acetyl-glucoside, cyanidin -3-O-hexoside, ellagic acid, quercetin, quercetin-3-O-glucoside, and apigenin glucoside. Intoxication of rats with TAA significantly elevated activities of serum AST, ALT, and ALP; concentrations of malondialdehyde, nitric oxide, and hepatic tissue protein expression of caspase 3 and COX2 with alteration of the histological structures of hepatic tissues, while it decreased serum levels of total protein, albumin, and hepatic tissue contents of reduced glutathione. Also, TAA intoxication resulted in 62.5% mortality in rats of G5. Treatment of TAA intoxicated rats (G4) with MOLE ameliorated the toxic effects of TAA on hepatic tissue structure and function. It decreased serum activities of AST, ALT, and ALP; enhanced hepatic GSH concentration; reduced pathological alterations and lipid peroxidation; and downregulated caspase 3 and COX2 proteins expression in hepatic tissue. In addition, MOLE protected rats of G6 from TAA-induced hepatic tissues injury and dysfunction, and increased survival rate of rats. In conclusion, MOLE had both ameliorating and protecting potentials against TAA-induced rats liver damage through regulation of antioxidant, anti-apoptotic, and inflammatory biomarkers. Graphical abstract.

Topics: Animals; Antioxidants; Biomarkers; Chemical and Drug Induced Liver Injury; Glucosides; Glutathione; Lipid Peroxidation; Liver; Male; Malondialdehyde; Moringa oleifera; Plant Extracts; Plant Leaves; Protective Agents; Quercetin; Rats; Rats, Wistar; Thioacetamide

To investigate the protective effect of enzymatically modified isoquercitrin (EMIQ) on the hepatocarcinogenic process, we used a two-stage hepatocarcinogenesis model in N-diethylnitrosamine-initiated and thioacetamide (TAA)-promoted rats. We examined the modifying effect of co-administration with EMIQ on the liver tissue environment including hepatic macrophages and lymphocytes and on the induction mechanism of preneoplastic cell apoptosis during early stages of hepatocellular tumor promotion. TAA increased the number and area of glutathione S-transferase placental form (GST-P)(+) liver cell foci and the numbers of proliferating and apoptotic cells in randomly selected areas in liver sections. Co-administration with EMIQ suppressed these effects. TAA also increased the numbers of ED2(+), cyclooxygenase-2(+), and heme oxygenase-1(+) liver cells, as well as the number of CD3(+) lymphocytes. These effects were also suppressed by EMIQ. EMIQ increased liver levels of thiobarbituric acid-reactive substance and 8-hydroxydeoxyguanosine, and TUNEL(+) apoptotic cells, death receptor 5 (DR5)(+) cells and 4-hydroxy-2-nonenal(+) cells within GST-P(+) foci. Outside the GST-P(+) foci, EMIQ decreased the numbers of apoptotic cells and DR5(+) cells. These results suggest that TAA-induced tumor promotion involves activation of hepatic macrophages producing proinflammatory factors. EMIQ may suppress the TAA-induced tumor-promoting activity by an anti-inflammatory mechanism mediated by suppressing the activation of these macrophages. Furthermore, EMIQ may suppress tumor-promoting activity differentially between the inside and outside of GST-P(+) foci. Within GST-P(+) foci, EMIQ facilitates the apoptosis of preneoplastic cells through the upregulation of DR5. Outside the GST-P(+) foci, EMIQ suppresses apoptosis and the subsequent regeneration of non-transformed liver cells.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Apoptosis; Carcinogens; Cell Line, Tumor; Deoxyguanosine; Diethylnitrosamine; Glutathione; Immunohistochemistry; In Situ Nick-End Labeling; Liver Neoplasms, Experimental; Lymphocytes; Macrophages; Male; Precancerous Conditions; Proliferating Cell Nuclear Antigen; Quercetin; Rats; Rats, Inbred F344; Real-Time Polymerase Chain Reaction; Receptors, TNF-Related Apoptosis-Inducing Ligand; Thioacetamide; Thiobarbituric Acid Reactive Substances