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      Evaluation of Acute and Sub-Acute Toxicity of Aqueous Extracts of Artemisia afra Leaves on Brain, Heart and Suprarenal Glands in Swiss Albino Mice

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          Abstract

          Background

          The majority of population rely on traditional medicine as a source of healthcare. Artemisia afra is a plant traditionally used for its medicinal values, including treatment of malaria in many parts of the world. Currently, it is also attracting attention because of a claim that a related species, Artemisia annua, is a remedy for the COVD-19 pandemic. The aim of the present study was to investigate toxic effects of A. afra on brain, heart and suprarenal glands in mice aged 8–12 weeks and weighing 25–30g.

          Methods

          Leaves of A.afra were collected from Bale National Park, dried under shade, crushed into powder and soaked in distilled water to yield aqueous extract for oral administration. For acute toxicity study, seven treated and one control groups, with 3 female mice each, were used. They were given a single dose of 200mg/kg, 700mg/kg, 1200mg/kg, 2200mg/kg, 3200mg/kg, 4200mg/kg or 5000mg/kg b/wt of the extract. For the sub-acute toxicity study, two treated and one control groups, with 5 female and 5 male mice each, were used. They were daily treated with 600mg/kg or 1800mg/kg b/wt of extract.

          Results

          LD 50 was found to be greater than 5000mg/kg indicating that the plant is relatively safe. In the sub-acute study, no signs of toxicity were observed in all treatment groups. On microscopic examination of the brain, heart and suprarenal glands no sign of cellular injury was observed.

          Conclusion

          The findings of this study suggest that the leaves extract of A. afra is relatively safe in mice.

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          Most cited references25

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          Relationships between organ weight and body/brain weight in the rat: what is the best analytical endpoint?

          Analysis of organ weight in toxicology studies is an important endpoint for identification of potentially harmful effects of chemicals. Differences in organ weight between treatment groups are often accompanied by differences in body weight between these groups, making interpretation of organ weight differences more difficult. Using data from control rats that were part of 26 toxicity studies conducted under similar conditions, we have evaluated the relationship between organ weight and body/brain weight to determine which endpoint (organ weight, organ-to-body weight ratio, or organ-to-brain weight ratio) is likely to accurately detect target organ toxicity. This evaluation has shown that analysis of organ-to-body weight ratios is predictive for evaluating liver and thyroid gland weights, and organ-to-brain weight ratios is predictive for evaluating ovary and adrenal gland weights. Brain, heart, kidney, pituitary gland, and testes weights are not modeled well by any of the choices, and alternative analysis methods such as analysis of covariance should be utilized.
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            Acute toxicity study of the standardized methanolic extract of Mitragyna speciosa Korth in rodent.

            Mitragyna speciosa Korth (ketum) is widely used in Malaysia as a medicinal agent for treating diarrhea, worm infestations and also acts as an analgesic and antipyretic. The aim of the study is to determine the acute toxicity of Mitragyna speciosa Korth standardized methanol extract in vivo in 4-weeks-old Sprague-Dawley rats. Rats were orally administrated single dose of 100, 500 and 1000 mg/kg Mitragyna speciosa Korth standardized methanol extract and the control group received 430 mg/kg of morphine orally. There were 10 rats in each group. All animals were sacrificed after 14 days of treatment. Eight parameters were tested: cage side observation, body weight measurement, food and water consumption, blood pressure, absolute and relative organ weight, hematology, biochemical analysis and histopathology, to look for evidence of toxicity. No mortality was noted after 14 days of treatment. In general, behavior, food and water consumption, hematological studies and organ weights showed no significant changes. The standardized methanol extraction of Mitragyna speciosa Korth increased rat blood pressure (systolic: 147.4+/-1.01, 131.64+/-4.94 and 137.8+/-4.46) after an hour of 100, 500 and 1000 mg/kg doses, respectively. Biochemical studies showed significant elevation of ALT, AST, albumin, triglycerides, cholesterol and albumin (p>0.05), at all levels of doses. But, nephrotoxicity evidenced by elevated creatinine was seen only at a dose of 1000 mg/kg. Histological examination showed congestion of sinusoids, hemorrhage hepatocytes, fatty change, centrilobular necrosis and increased number of Kuppfer cells in the liver of all Mitragyna speciosa Korth standardized methanol extract treated groups. Oral administration of standardized methanolic extraction of Mitragyna speciosa Korth resulted in increasing rat blood pressure after an hour of drug administration. The highest dose of extract also induced acute severe hepatotoxicity and mild nephrotoxicity. However, Mitragyna speciosa Korth shows no effects on body weight, food and water consumption, absolute and relative organ weight and also hematology parameters. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
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              A 90-day oral gavage toxicity study of D-methylphenidate and D,L-methylphenidate in Sprague-Dawley rats.

              D-methylphenidate is an enantiomer of D,L-methylphenidate and was developed as an improved treatment for attention deficit hyperactivity disorder in children. The current study was performed to determine and compare the toxicity of 2-50 mg/kg per day D-MPH and 100 mg/kg per day D,L-MPH for 90 days in rats with the top D-MPH dose being equimolar to 100 mg/kg D,L-MPH. The top D-MPH and D,L-MPH doses were at least 67 times that of the human dose and produced systemic exposures that were over 10 times higher than those typically achieved in children. During the course of the study, one male each from the 50 mg/kg per day and D,L-MPH groups and one female from the 50 mg/kg group died. Incidences of material around nose/eyes, scabbing, foot swelling, alopecia and abrasions were evident at 50 mg/kg per day D-MPH and 100 mg/kg per day D,L-MPH doses. Body weight and its changes decreased in a dose-dependent manner for D-MPH males. There were significant changes in some clinical chemistry measurements at the terminal bleed in the high dose groups of both sexes although most of these changes were resolved by the recovery bleed. Differences in absolute and relative body and certain organ weights for high dose D-MPH and D,L-MPH groups were seen at terminal necropsy with the differences no longer present after the recovery period. No abnormal or gross histopathological changes were associated with any of these organ weight changes reported for the terminal and recovery periods. Based on body weight changes, the no observed adverse effect level for D-MPH in rats was 20 mg/kg. Overall, the toxicity profile observed in rats with 50 mg/kg per day D-MPH was comparable to that of an equimolar dose of D,L-MPH (100 mg/kg per day) when given repeatedly for 90 days using a twice a day dosing regimen.
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                Author and article information

                Journal
                Ethiop J Health Sci
                Ethiop J Health Sci
                Ethiopian Journal of Health Sciences
                Research and Publications Office of Jimma University (Jimma, Ethiopia )
                1029-1857
                2413-7170
                November 2020
                : 30
                : 6
                : 981-990
                Affiliations
                [1 ] Department of Anatomy, College of Health Sciences, Debermarkos University, Ethiopia
                [2 ] Department of Anatomy, College of Health Sciences, Addis Ababa University, Ethiopia
                [3 ] Department of Pharmacology, College of Health Sciences, Addis Ababa University, Ethiopia
                [4 ] Center for Innovative Drug Development and Therapeutic Trials for Africa, College of Health Sciences, Addis Ababa University, Ethiopia
                [5 ] Ethiopian Public Health Institute, Ethiopia
                [6 ] Department of Pathology, College of Health Sciences, Addis Ababa University, Ethiopia
                [7 ] Department of physiology, College of Health Sciences, Addis Ababa University, Ethiopia
                Author notes

                Funding: Nil

                Competing Interests: The authors declare that this manuscript was approved by all authors in its form and that no competing interest exists.

                Article
                jEJHS.v30.i6.pg981
                10.4314/ejhs.v30i6.16
                8047245
                33883843
                b62ff3b0-aff1-4d1c-b841-a8c7056702f7
                © 2020 Ketema Mekonnen., et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 21 May 2020
                : 22 June 2020
                Categories
                Original Article

                Medicine
                a. afra,toxicity study,histopathology,brain,heart,suprarenal glands,swiss albino mice
                Medicine
                a. afra, toxicity study, histopathology, brain, heart, suprarenal glands, swiss albino mice

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