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      In vitro Antioxidant and in vivo Hepatoprotective Activities of Root Bark Extract and Solvent Fractions of Croton macrostachyus Hochst. Ex Del. ( Euphorbiaceae) on Paracetamol-Induced Liver Damage in Mice

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          Abstract

          Background

          Liver disease is a major public health threat, particularly in developing countries. Several medicinal plants and formulations have been claimed to have liver protective activities. The present study aimed to evaluate in vitro antioxidant and in vivo hepatoprotective activities of root bark extracts of Croton macrostachyus (Euphorbiaceae).

          Methods

          Free radical scavenging activity of crude extract and solvent fractions of the plant was conducted using the DPPH assay method. Hepatoprotective activities of the crude extract and solvent fractions of the plant were carried out based on paracetamol-induced liver damage in mice. Serum biomarkers (AST, ALT, ALP, total bilirubin and total protein) were assessed to find out the effect. Histopathological examination was also carried out for all groups of mice to further confirm the findings.

          Results

          Antioxidant assay revealed that the crude extract, aqueous fraction and chloroform fraction of Croton macrostachyus exhibited free radical scavenging activity with IC 50 values of 128.6, 168.9, and 406 µg/mL, respectively. Pretreatment of the mice with the crude extract and solvent fractions of Croton macrostachyus significantly reduced ALP (p<0.001), ALT (p<0.001), and AST (p<0.001) levels at all the administered doses compared to the toxic group. The crude extract and chloroform fraction decreased total bilirubin level at doses of 200 mg/kg (P<0.05) and 400 mg/kg (P<0.001). Pretreatment of the mice with 400 mg/kg of the crude extract and aqueous fraction elevated total protein value compared to the paracetamol treated group (P<0.05). The hepatoprotective activities of the plant extracts were confirmed by histopathological studies.

          Conclusion

          From this study, it can be concluded that the crude extract and solvent fractions of Croton macrostachyus demonstrated antioxidant and hepatoprotective activities.

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          Most cited references50

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          Antioxidant principles from Bauhinia tarapotensis.

          A new cyclohexenone (1) and a new caffeoyl ester derivative (2), together with the known compounds (-)-isolariciresinol 3-alpha-O-beta-D-glucopyranoside (3), (+)-1-hydroxypinoresinol 1-O-beta-D-glucopyranoside (4), isoacteoside (5), luteolin 4'-O-beta-D-glucopyranoside (6), and indole-3-carboxylic acid (7), were isolated from the leaves of Bauhinia tarapotensis. The structures of these new compounds were determined by spectroscopic data analysis. The antioxidant activities of 1-7 were determined by measuring their free radical scavenging effects, using the 1,1-diphenyl-2-dipicrylhydrazyl free radical (DPPH) and Trolox equivalent antioxidant activity (TEAC) methods, and the coupled oxidation of beta-carotene and linoleic acid. Compounds 3-5 showed good activities in the DPPH and TEAC tests, while compounds 1 and 2 were active in the coupled oxidation of beta-carotene and linoleic acid bioassay.
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            An ethnobotanical study of medicinal plants in Mana Angetu District, southeastern Ethiopia

            This study documents indigenous medicinal plant utilization, management and the threats affecting them. The study was carried out in Mana Angetu district between January 2003 and December 2004. Ethnobotanical data were collected using semi structured interviews, field observations, preference and direct matrix ranking with traditional medicine practitioners. The ethnomedicinal use of 230 plant species was documented in the study area. Most of the plants (78.7%) were reportedly used to treat human diseases. The most frequently used plant part were roots (33.9%), followed by leaves (25.6%). Most of the medicinal species (90.4%) were collected from the wild. Direct matrix analysis showed that Olea europaea L. Subsp. cuspidata (Wall. ex G. Don) was the most important species followed by Acacia tortilis (Forssk.) Hayne (120) indicating high utility value of these species for the local community. The principal threatening factors reported were deforestation (90%), agricultural expansion (85%) and fire (53%). Documenting the eroding plants and associated indigenous knowledge can be used as a basis for developing management plans for conservation and sustainable use of medicinal plants in the area.
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              Acetaminophen: Dose-Dependent Drug Hepatotoxicity and Acute Liver Failure in Patients

              Background: Drug-induced liver injury is a rare but serious clinical problem. A number of drugs can cause severe liver injury and acute liver failure at therapeutic doses in a very limited number of patients (<1:10,000). This idiosyncratic drug-induced liver injury, which is currently not predictable in preclinical safety studies, appears to depend on individual susceptibility and the inability to adapt to the cellular stress caused by a particular drug. In striking contrast to idiosyncratic drug-induced liver injury, drugs with dose-dependent hepatotoxicity are mostly detected during preclinical studies and do not reach the market. One notable exception is acetaminophen (APAP, paracetamol), which is a safe drug at therapeutic doses but can cause severe liver injury and acute liver failure after intentional and unintentional overdoses. Key Messages: APAP overdose is responsible for more acute liver failure cases in the USA or UK than all other etiologies combined. Since APAP overdose in the mouse represents a model for the human pathophysiology, substantial progress has been made during the last decade in understanding the mechanisms of cell death, liver injury and recovery. More recently, emerging evidence based on mechanistic biomarker analysis in patients and studies of cell death in human hepatocytes suggests that most of the mechanisms discovered in mice also apply to patients. The rapid development of N-acetylcysteine as an antidote against APAP overdose was based on the early understanding of APAP toxicity in mice. However, despite the efficacy of N-acetylcysteine in patients who present early after APAP overdose, there is a need to develop intervention strategies for late-presenting patients. Conclusions: The challenges related to APAP toxicity are to better understand the mechanisms of cell death in order to limit liver injury and prevent acute liver failure, and also to develop biomarkers that better predict as early as possible who is at risk for developing acute liver failure with poor outcome.
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                Author and article information

                Journal
                J Exp Pharmacol
                J Exp Pharmacol
                jep
                jexpharm
                Journal of Experimental Pharmacology
                Dove
                1179-1454
                26 August 2020
                2020
                : 12
                : 301-311
                Affiliations
                [1 ]Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, Mekelle University , Mekelle, Ethiopia
                [2 ]Department of Pharmacology, JKK Nattraja College of Pharmacy , Komarapalayam 638 183, Tamilnadu, India
                Author notes
                Correspondence: Kald Beshir Tuem Tel +251920425426 Email kalizad2003@gmail.com
                Author information
                http://orcid.org/0000-0002-6274-0106
                http://orcid.org/0000-0003-2847-1392
                Article
                259081
                10.2147/JEP.S259081
                7493212
                32982486
                b6f51cea-59ae-4f8e-ba6d-0471b14485f3
                © 2020 Tafere et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 20 April 2020
                : 04 August 2020
                Page count
                Figures: 1, Tables: 10, References: 56, Pages: 11
                Funding
                Funded by: Mekelle University;
                This work was funded by Mekelle University.
                Categories
                Original Research

                antioxidant,hepatoprotective,croton macrostachyus,paracetamol,biochemical parameters,liver damage

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