In this study, thein vitroantimicrobial activities of four plant essential oils (T. schimperi,E. globulus,R. officinalis, andM. Chamomilla) were evaluated against bacteria and fungi. The studies were carried out using agar diffusion method for screening the most effective essential oils and agar dilution to determine minimum inhibitory concentration of the essential oils. Results of this study revealed that essential oils ofT. schimperi,E. globulus, andR. officinaliswere active against bacteria and some fungi. The antimicrobial effect ofM. chamomillawas found to be weaker and did not show any antimicrobial activity. The minimum inhibitory concentration values ofT. schimperiwere<15.75 mg/mL for most of the bacteria and fungi used in this study. The minimum inhibitory concentration values of the other essential oils were in the range of 15.75–36.33 mg/mL against tested bacteria. This study highlighted the antimicrobial activity of the essential oil ofE. globulus,M. chamomilla,T. Schimperi, andR. officinalis. The results indicated thatT. schimperihave shown strong antimicrobial activity which could be potential candidates for preparation of antimicrobial drug preparation.

Cymbopogon citratus has been used by the local people in Ankober district, northern Ethiopia, as traditional medicine to treat various ailments. Its essential oil has been shown to have antibacterial, antifungal, antiprotozoal, anti-carcinogenic, anti-inflammatory and antioxidant activities amongst others. This study was conducted to determine skin irritation, acute and subacute toxicity of C. citratus essential oil in mice and rabbits. The essential oil was analyzed using GC-MS. The essential oil at dose of 2000 mg/kg body weight was administered to mice for 21 consecutive days. The mice mortality, behavioral change, injury and other signs of illness were recorded once daily. Biochemical parameters were evaluated. Liver and kidney were taken after sacrifice for gross findings and histological analyses. 10 % ointment formulation of C. citratus oils was applied on the rabbit skin to determine skin irritation effects. The result revealed, the presence of citral (71.297%), myrcene (19.034%), 4, 5-epoxycarene (2.780%), linalool (1.713%), ((S)-cis-verbenol (1.110 %), linalool (1.713 %), ((S)-cis-verbenol (1.110 %) and undecan-2-one (1.001 %) in the C. citratus essential oil. There was no significant difference (p > 0.05) in the body weights, gross abnormalities of the organs and biochemical parameters compared to the control. No histopathological changes were detected in the organs tested. 10 % ointment formulation of C. citratus oils did not cause skin irritation. Analysis of results leads to the conclusion that Ethiopian C. citratus essential oil may be considered as relatively safe and non-toxic.

Lavandula angustifolia is used in traditional and folk medicines of Ankober District, North Central Ethiopia, for the treatment of several livestock and human disorders. This toxicity study aimed to investigate L. angustifolia essential oil oral toxicity in mice and skin irritation in rabbit. L. angustifolia essential oil was analyzed using gas chromatography-mass spectrometry methods and showed predominance of Eucalyptol (52.36%), Camphor (11.91%), gamma-terpinene (8.775%) and endoborneol (7.585%). Limit test at 2000 mg/kg dose was used for L. angustifolia essential oil acute toxicity test and revealed LD₅₀ value was higher than 2000 mg/kg. For subacute toxicity study 2000mg/kg was given orally to each mouse for 21 days. The result demonstrated no significant changes (p > 0.05) in the body weights, and biochemical parameters, gross abnormalities, water, and food intake were observed. No macroscopic changes were seen in the histopathology analysis of kidneys and livers. For skin irritation test shaved rabbit skin was treated with 10% ointment formulation. Ointment of L. angustifolia oil did not affect mice skin. Generally, this toxicity study demonstrated that L. angustifolia essential oil is nontoxic.

In Ankober, Northern Ethiopia, Rosmarinus officinalis has been commonly used for flavoring foods as a condiment; moreover, the plant has also been widely used for different medicinal purposes. The current study was undertaken to provide data on acute and subacute toxicity in mice as well as skin irritation of R. officinalis essential oil in rabbit. Acute dermal and oral toxicity tests were conducted using limited dose of 2000 mg/kg. In sub-acute study, 1000 mg/kg were given by gavage to mice for 28 consecutive days. The mice were weighed and various observations like mortality, behavior, injury, or any signs of illness were conducted once daily during the study period. At the end of each study, biochemical parameters were evaluated and kidney and liver were taken after sacrifice for gross findings and histological analyses. For dermal toxicity, 10% ointment formulation of oils was applied on the rabbit skin to evaluate whether the animals sustained significant skin damage. The LD50 of R. officinalis essential oil for both dermal and oral administration is greater than 2000 mg/kg. There was no significant difference (p > 0.05) observed in the body weights, biochemical parameters, and gross abnormalities, as compared to the control in subacute study. No mortality was recorded. Pathological studies showed that there were no any macroscopic changes in kidneys and liver and all of them have normal appearance. The data of acute skin irritation test demonstrated that 10% R. officinalis oils ointment formulation did not induce acute toxicity in the skin of the animals. Overall, the findings of this study indicate that R. officinalis essential oil is non-toxic. Key words: Rosmarinus officinalis, skin irritation, acute dermal toxicity, acute oral toxicity, subacute toxicity, biochemical analysis, histopathology.

Introduction: Genetic variation in the thiopurine S-methyltransferase (TPMT) gene by and large predicts variability in 6-mercaptopurine (6-MP) related toxicities. However, some individuals without genetic variants in TPMT still develop toxicity that necessitates 6-MP dose reduction or interruption. Genetic variants of other genes in the thiopurine pathway have been linked to 6-MP related toxicities previously.Objective: The aim of this study was to evaluate the effect of genetic variants in ITPA, TPMT, NUDT15, XDH, and ABCB1 on 6-MP related toxicities in patients with acute lymphoblastic leukemia (ALL) from Ethiopia.Methods: Genotyping of ITPA, and XDH was performed using KASP genotyping assay, while that of TPMT, NUDT15, and ABCB1 with TaqMan^® SNP genotyping assays. Clinical profile of the patients was collected for the first 6 months of the maintenance phase treatment. The primary outcome was the incidence of grade 4 neutropenia. Bivariable followed by multivariable cox regression analysis was performed to identify genetic variants associated with the development of grade 4 neutropenia within the first 6 months of maintenance treatment.Results: In this study, genetic variants in XDH and ITPA were associated with 6-MP related grade 4 neutropenia and neutropenic fever, respectively. Multivariable analysis revealed that patients who are homozygous (CC) for XDH rs2281547 were 2.956 times (AHR 2.956, 95% CI = 1.494–5.849, p = 0.002) more likely to develop grade 4 neutropenia than those with the TT genotype.Conclusion: In conclusion, in this cohort, XDH rs2281547 was identified as a genetic risk factor for grade 4 hematologic toxicities in ALL patients treated with 6-MP. Genetic polymorphisms in enzymes other than TPMT involved in the 6-mercaptopurine pathway should be considered during its use to avoid hematological toxicity.

Introduction: The maintenance phase of acute lymphoblastic leukemia treatment is the final and longest stage of treatment, mainly focused on antimetabolite therapy. This phase is essential to eliminate residual leukemic clones and prevent relapse. However, dose-limiting hematotoxicity is a major problem during this phase resulting in dose reduction or treatment discontinuation. Objective: In this cohort study, the clinical features and risk factors of hematological toxicity during the maintenance phase of treatment were analyzed in pediatric patients from Ethiopia. Methods: A total of 160 patients from Tikur Anbessa specialized hospital were included in the study of which 142 had sufficient data available for analysis. Patient characteristics as well as information about the care-givers, sides-effects as reported by the care-givers and clinical factors were collected. Bivariable followed by multivariable analysis was performed to investigate which factors were associated with hematological toxicity during the maintenance phase. Results: During the first six months of maintenance phase treatment grade 4 neutropenia was detected in 52.8% of the patients. The risk of developing grade 4 neutropenia was increased by about two fold in children with the age of 6 years and less compared to those with the age of more than 6 years. Similarly, the rate of developing grade 4 neutropenia among children with less than 4,500 maintenance day 1 white blood cell counts was significantly higher than that of children with normal maintenance day 1 white blood cell counts (AHR 2.477, 95% CI = 1.461–4.200, p = 0.001). Conclusion: In conclusion, child’s age and day 1 maintenance white blood cell/absolute neutrophil counts significantly affected the occurrence of grade 4 hematotoxicity. Close monitoring for white blood cell and absolute neutrophil counts during maintenance phase treatment is recommended for early diagnosis of hematotoxicity.