Flavonoids have been shown to have antioxidant factors and effective against hepatotoxicity. This in vivo study aimed to evaluate the efficacy of flavonoids rich extracts in a model of chemicalinduced liver cell injury. Materials and Methods: Flavonoids were extracted from leaves and flowers of Arbutus pavarii using Microwave assisted extraction method. Different concentrations of extracted flavonoids (200, 500, 1000, 2000 and 5000mg/kg bw) were evaluated up to two weeks on mice model. The hepatoprotective effects of the extracts were examined using mice pretreated orally with 200 and 400 mg/kg bw of flavonoids extracted from leaves and flowers as well as their combination (200 mg/kg; 1:1) for 28 days. At day 28, the mice were received orally a single dose of 1ml/kg CCl4 in corn oil. Forty-eight hours after Carbon tetrachloride (CCl4) treatment, the animals were sacrificed and their liver and blood samples were collected for determination of biochemical parameters (Alkaline phosphatase (ALT), Aspartate-aminotransferase (AST) and Alanine-aminotransferase (ALP)), histopathological investigation and antioxidant status. Results: Treatment of the mice with a daily dose of flavonoids extracts up to 5 g/kg bw did not cause mortality and did not show hepatotoxicity. Pretreatment with extracts decreased the increased serum levels of ALT, AST, and ALP, decreased lipid peroxidation and maintained the levels of glutathione and antioxidant enzymes status in the CCl4 treated mice, especially in the group treated with combined extracts. The hepato-protcitve effects were confirmed by histopathological examinations. Conclusion: The results shown by the extracted flavonoids need further investigation.
Rabia Alghazeer, Sana Elgahmasi, Abdul Hakim Elnfati, Mohamed Elhensheri, Mohamed A. Al-Griw, Nuri Awayn, Mariuma El- Nami(3-2018)

The goal of this study was to investigate, in-vivo, the predominant mechanism of cell death, apoptosis versus necrosis, in the mature mouse brain exposed early to a ubiquitous environmental toxicant trichloroethane (TCE). A subset of male albino mice was injected intraperitoneally twice weekly for three weeks with TCE (100 and 400µg/kg). All animals were followed up for signs of toxicity and mortality. Changes in neural tissues were histpathologically evaluated. Biomarkers of brain cell number were also studied. The results showed that TCE insult triggered significant alterations in the microstructure of the brain tissues compared to controls. Mitotic figures and apoptotic changes such as chromatin condensation and nuclear fragments were also identified. Cell death analysis demonstrates that cell apoptosis with necrosis was evident in the TCE-treated groups. The percent of necrosis was quantified as 20.09 ± 2.57% at 100µg/kg TCE, 30.57 ± 5.18% at 400µg/kg TCE, and 12.67 ± 1.25% in controls. However, the percent of apoptosis was quantified as 29.18 ± 1.51% at 100µg/kg TCE, 20.14 ± 2.12% at 400µg/kg TCE, and 8 ± 1.25% in controls. There was also a significant reduction in the brain DNA content in the TCE-treated groups. Agarose gel electrophoresis is also provided further biochemical evidence of apoptosis by showing internucleosomal DNA fragmentation. These results correlated with neurobehavioral impairment. These findings indicate that TCE induces degeneration and apoptotic cell death in mouse brain, suggesting a crucial role played by apoptosis in TCE neurotoxicity.
Mohamed A. Al-Griw, Abdul Hakim Elnfati, Naser M. Salama, Massaud S. Maamar, Soad A. Treesh, Taher Shaibi(10-2015)

Alterations in genes encoding the xenobiotic-metabolizing enzymes contribute to the variability in susceptibility to various cancers. In this study, we assessed the possible association between the CYP1A1 variants and lung cancer (LC) risk in a population of Libyan males. For this study, we selected 20 unrelated healthy controls and 32 patients with LC. DNA samples from the controls and patients were screened by DNA-PCR and direct DNA sequence analysis to search for genetic sequence variations in CYP1A1 gene (exon 7 and 3’ non-coding region). CYP1A1 mutations were identified in 11.5 % adult subjects and cases analyzed, and all were males. Overall, 11 CYP1A1 mutations were documented in this study implicating exon 7 and 3’ non-coding region. Nonsense, missense, and frame-shift mutations accounted for, respectively, 27.3 %, 63.6 % and 9.1 % of all CYP1A1 mutations. Three missense mutations namely CYP1A1*2B/m2 (rs1048943), CYP1A1*4/m4 (rs1799814), and CYP1A1*2A/m1 (rs4646903) have already been reported. The remaining mutations have not been described previously. We observed two apparently heterozygous carriers of mutation CYP1A1*2B/m2 (CYP1A1 4889A/G [642Ile/Val] genotype) in control group. We also observed two heterozygotic genotypes one containing mutation m4 (CYP1A1 4887C/A [461Thr/Asp]) and another containing mutation m1 (6235T/C) in cancer group. The mutations m2, m4, and m1 accounted for, respectively, 18.2 %, 9.1 % and 9.1 % of all CYP1A1 mutations. Comparing the clinical features showed that PLT and WBC counts were lower in CYP1A1 mutant than in CYP1A1 wild type, but they have not reached statistical significant (P > 0.05). The average age of CYP1A1 mutant was lower than in CYP1A1 wild type. Overall, these findings suggest that genetic alterations in the metabolic gene CYP1A1 are too rare to be of clinical relevance in this study, implying different pathways for the LC risk with respect to CYP1A1 polymorphisms as a risk factor for LC at least in this study.
Najah A. Fares, Othman A. El-Ansari, Mohamed A. Al-Griw(4-2017)