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)

Reactive gliosis and inflammation are risk factors for white matter injury (WMI) development, which are correlated with the development of many neurodevelopmental deficits with no treatment. This study aimed to understand the mechanisms correlated with WMI, with a particular focus on the role of nuclear factor‑kappa B (NF‑kB) and p38 mitogen‑activated protein kinases (MAPKs) pathways. Seven‑day‑old Wistar rats were used to generate cerebellar tissue slices. Slices were cultured and randomly allocated to one of 3 groups and treated as follows: group‑I (control); group‑II (WMI), slices were subjected to 20 min of oxygen‑glucose deprivation (OGD); group‑III (WMI+ blockers), slices were subjected to OGD and treated with the blockers. Results showed that OGD insult triggered a marked increase in the apoptosis among WM elements, as confirmed by TUNEL assay. Immunocytochemical experiments revealed that there was a significant decrease in the percent of MBP+ OLs and NG2+ OPCs, and myelin integrity. There was also a significant increase in the percent of reactive microglia and astrocytes. BrdU immunostaining revealed there was an increase in the percent of proliferating microglia and astrocytes. Q‑RT‑PCR results showed OGD upregulated the expression levels of cytokines (TNF‑α, IL‑1, IL‑6, and IL‑1β) and inducible nitric oxide synthase (iNOS). On the other hand, treatment with BAY11 or SB203580 significantly enhanced the OL survival, restored myelin loss, and reduced microglia and astrocyte reactivity, and downregulated the iNOS and cytokine expression. Our findings demonstrate that blocking of NF‑KB/p38 MAPK pathways alleviated reactive gliosis, inflammation, and OL loss upon WMI. The findings may help to develop therapeutic interventions for WMI.
Mohamed A. Al-Griw, Michael G. Salter, Ian C. Wood(1-2022)

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)