PT - JOURNAL ARTICLE AU - Miriam Watafua AU - Jane I. Ejiofor AU - Aminu Musa AU - Mubarak Hussaini Ahmad TI - <em>Acacia sieberiana</em> (Fabaceae) Attenuates Paracetamol and Bile Duct Ligation-Induced Hepatotoxicity via Modulation of Biochemical and Oxidative Stress Biomarkers AID - 10.1101/2022.06.22.497272 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.06.22.497272 4099 - http://biorxiv.org/content/early/2022/06/26/2022.06.22.497272.short 4100 - http://biorxiv.org/content/early/2022/06/26/2022.06.22.497272.full AB - Background The plant Acacia sieberiana (Fabaceae) is traditionally used to manage hepatitis. This research work aims to investigate the hepatoprotective effectiveness of root bark extract of Acacia sieberiana (ASE) against paracetamol (PCM) and bile duct ligation (BDL)-induced hepatotoxicity. The phytochemical and median lethal dose (LD50) investigations were conducted. The rats were pre-treated with the ASE (250, 750, 1,500 mg/kg) once daily via oral route for 7 consecutive days. On the 8th day, liver injury was initiated by PCM administration (2g/kg). Similarly, in the BDL-induced liver injury, the animals were administered ASE (125, 250 and 380 mg/kg) intraperitoneally for 7 consecutive days. After 24 hours, blood samples and hepatic tissues were obtained for biochemical and histopathological investigations.Results Phytocomponents determination revealed glycosides, triterpenes, glycosides, saponins, tannins, flavonoids and alkaloids. The oral and intraperitoneal LD50 values of the ASE were &gt;5,000 and 1,300 mg/kg, respectively. The ASE efficiently (p&lt;0.05) decreased the alanine transaminase (ALT) and aspartate transaminase (AST) levels and elevated the albumin and total protein (TP) levels. The direct bilirubin effectively (p&lt;0.05) decreased at 750 mg/kg. Besides, the extract efficiently elevated the glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) in relation to the PCM hepatotoxic group. Also, the malondialdehyde (MDA) concentration was reduced by the ASE. Meanwhile, in the BDL– induced liver injury, the ASE remarkably (p&lt;0.05) declined the AST, ALP, bilirubin and MDA. Besides, there was effective (p&lt;0.05) elevation in SOD, GPx and CAT in the ASE-treated groups. The morphology of liver tissue was preserved at 125 and 250 mg/kg ASE groups from BDL-induced necrosis and vascular congestion.Conclusion The study shows that the ASE has hepatoprotective actions against liver damage by possible modulation of biochemical and oxidative stress biomarkersCompeting Interest StatementThe authors have declared no competing interest.ABUAhmadu Bello UniversityABUCAUCABU Ethical Committee on Animal Use and Care Research PolicyALPAlkaline phosphataseALTAlanine transaminaseNOVAAnalysis of varianceARRIVEAnimal Research: Reporting of In Vivo ExperimentsASEAcacia sieberiana extractASTaspartate transaminaseBDLBile duct ligationCATCatalaseDBDirect bilirubinDWDistilled waterFNFocal necrosisGPxGlutathione peroxidasei.pIntraperitonealKHKupffer cell hyperplasiaLD50Medial lethal doseLHLymphocytes hyperplasiaMDAMalondialdehydeMNModerate necrosisNNecrosisNAPQIN-acetyl-p-benzoquinonyminNHNormal hepatocytesPCMParacetamolROSReactive oxygen speciesrpmRevolutions per minuteSCSinusoid congestionSCslight sinusoidal congestionSEMStandard error of the meanSNSlight necrosisSODSuperoxide dismutaseTBTotal bilirubinTPTotal proteinVCVascular congestion