Environmental toxicants such as chemicals, heavy metals, and pesticides have been shown to promote transgenerational inheritance of abnormal phenotypes and/or diseases to multiple subsequent generations following parental and/ or ancestral exposures. This study was designed to examine the potential transgenerational action of the environmental toxicant trichloroethane (TCE) on transmission of liver abnormality, and to elucidate the molecular etiology of hepatocyte cell damage. A total of thirty two healthy immature female albino mice were randomly divided into three equal groups as follows: a sham group, which did not receive any treatment; a vehicle group, which received corn oil alone, and TCE treated group (3 weeks, 100 μg/kg i.p., every 4th day). The F0 and F1 generation control and TCE populations were sacrificed at the age of four months, and various abnormalities histpathologically investigated. Cell death and oxidative stress indices were also measured. The present study provides experimental evidence for the inheritance of environmentally induced liver abnormalities in mice. The results of this study show that exposure to the TCE promoted adult onset liver abnormalities in F0 female mice as well as unexposed F1 generation offspring. It is the first study to report a transgenerational liver abnormalities in the F1 generation mice through maternal line prior to gestation. This finding was based on careful evaluation of liver histopathological abnormalities, apoptosis of hepatocytes, and measurements of oxidative stress biomarkers (lipid peroxidation, protein carbonylation, and nitric oxide) in control and TCE populations. There was an increase in liver histopathological abnormalities, cell death, and oxidative lipid damage in F0 and F1 hepatic tissues of TCE treated group. In conclusion, this study showed that the biological and health impacts of environmental toxicant TCE do not end in maternal adults, but are passed on to offspring generations. Hence, linking observed liver abnormality in the offspring to environmental exposure of their parental line. This study also illustrated that oxidative stress and apoptosis appear to be a molecular component of the hepatocyte cell injury.
Mohamed A. Al-Griw , Soad A. Treesh, Rabia O. Alghazeer, Sassia O. Regeai (7-2017)

Efficient extraction of genomic DNA (gDNA) from biological materials found in harsh environments is the first step for successful forensic DNA profiling. This study aimed to evaluate two methods for DNA recovery from animal tissues (livers, muscles), focusing on the best storage temperature for DNA yield in term of quality, quantity, and integrity for use in several downstream molecular techniques. Six male Swiss albino mice were sacrificed, liver and muscle tissues (n=32) were then harvested and stored for one week in different temperatures, -20C, 4C, 25C and 40C. The conditioned animal tissues were used for DNA extraction by Chelex-100 method or NucleoSpin Blood and Tissue kit. The extracted gDNA was visualized on 1.5% agarose gel electrophoresis to determine the quality of gDNA and analysed spectrophotometrically to determine the DNA concentration and the purity. Both methods, Chelex-100 and NucleoSpin Blood and Tissue kit found to be appropriate for yielding high quantity of gDNA, with the Chelex100 method yielding a greater quantity (P < 0.045) than the kit. At -20C, 4C, and 25C temperatures, the concentration of DNA yield was numerically lower than at 40C. The NucleoSpin Blood and Tissue kit produced a higher (P=0.031) purity product than the Chelex-100 method, particularly for muscle tissues. The Chelex-100 method is cheap, fast, effective, and is a crucial tool for yielding DNA from animal tissues (livers, muscles) exposed to harsh environment with little limitations.
Huda H. Al-Griw, Zena A. Zraba, Salsabiel K. Al-Muntaser, Marwan M. Draid, Aisha M. Zaidi, Refaat M. Tabagh , Mohamed A. Al-Griw(8-2017)

Exposures to a wide variety of environmental substances are negatively associated with many biological cell systems both in humans and rodents. Trichloroethane (TCE), a ubiquitous environmental toxicant, is used in large quantities as a dissolvent, metal degreaser, chemical intermediate, and component of consumer products. This increases the likelihood of human exposure to these compounds through dermal, inhalation and oral routes. The present in vivo study was aimed to investigate the possible cellular and molecular etiology of liver abnormality induced by early exposure to TCE using a murine model. The results showed a significant increase in liver weight. Histopathological examination revealed a TCE-induced hepatotoxicity which appeared as heavily congested central vein and blood sinusoids as well as leukocytic infiltration. Mitotic figures and apoptotic changes such as chromatin condensation and nuclear fragments were also identified. Cell death analysis demonstrates hepatocellular apoptosis was evident in the treated mice compared to control. TCE was also found to induce oxidative stress as indicated by an increase in the levels of lipid peroxidation, an oxidative stress marker. There was also a significant decrease in the DNA content of the hepatocytes of the treated groups compared to control. Agarose gel electrophoresis also provided further biochemical evidence of apoptosis by showing internucleosomal DNA fragmentation in the liver cells, indicating oxidative stress as the cause of DNA damage. These results suggest the need for a complete risk assessment of any new chemical prior to its arrival into the consumer market.
Mohamed M. Al-Griw, Rabia O. Alghazeer, S. A. Al-Azreg, Emad M. Bennour(9-2016)

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)

Mutations in the TAL1 (T-cell acute leukemia 1) gene were recently described in patients with T-cell acute lymphoblastic leukaemia (T-ALL) and in those with lymphoblastic T-cell non-Hodgkin’s lymphoma (T-NHL). The purpose of this pilot study was to assess the prevalence of mutations in TAL1 gene in T-ALL and TNHL. DNA samples from 15 unrelated healthy controls, 20 T-ALL patients, and 10 T-NHL patients were analyzed using DNA-PCR and direct DNA sequencing to identify sequence genetic variations in TAL1 gene (exons 2 and 3). TAL1 exon 2 mutations were identified in 7.7% adult and 12.5% adolescent T-ALL patients analyzed. TAL1 exon 2 mutations were detected in 16.7% of the adult TNHL patients analyzed. Sequencing of TAL1 exon 3 showed no sequence variation for the T-ALL and T-NHL cancer patients analyzed. No sex difference where observed in the incidences of TAL1 exons 2 mutations between T-ALL and T-NHL patients with and without TAL1 mutations. TAL1 exon 2 missense and frame-shift mutations were present in 44.4% (4/9) and 55.6% (5/9) of T-ALL patients, respectively. However, the frame-shift and missense mutations in the T-NHL patients accounted for, where respectively, 60% (3/5) and 40% (4/5) of all TAL1 exon 2 mutations. Comparing the clinical features showed that there are no differences in PLT and WBC counts as well as the average age between T-ALL and T-NHL patients with and without TAL1 mutations. Overall, these findings indicate that TAL1 mutations are too rare to be of clinical relevance, and do not seem to be significantly associated with the increased T-ALL and T-NHL susceptibility, implying different pathways with respect to TAL1 genetic polymorphisms as a risk factor for T-ALL and T-NHL at least in this population of Libyans.
Amal E. Elarifi, Othman A. El-Ansari, Mohamed A. Al-Griw(12-2016)

Ischaemic injury during brain development correlates with long-term neurological problems resulting in part from oligodendrocytes (OL) damage and a loss of appropriate myelination. The molecular and cellular mechanisms responsible remain partially understood and there is no effective clinical treatment. Here we develop and characterise an ex-vivo slice culture ischaemia model to elucidate the cellular mechanisms to aid the search for therapeutic interventions. Cerebellar slices from 7 day-old rats were cultured for 10 days and their developmental profile in culture and their response to oxygen-glucose deprivation (OGD) was assessed. During the culture period development of white matter progressed as in-vivo, the numbers of oligodendrocyte precursor cells (OPC) decreased and the numbers of mature OLs increased and there was extensive myelination of axons as judged by colocalisation of myelin basic protein and neurofilament. Cultured slices were exposed to a short period of OGD at 7 days in-vitro and reperfused to mimic in-vivo conditions. Twenty minutes of OGD was found to result in significant injury as judged by a 58.6% reduction in cell viability 3 days post-injury. Treatment of cultures with OGD resulted in a loss of OLs and a loss of myelination of axons. In summary we have developed a paradigm for studying the damage to OLs and loss of myelination associated with ischaemic periods during development which should facilitate the search for understanding the mechanisms responsible and identifying potential therapeutic interventions.
Mohamed A M Al Griw , Mohamed A. Al-Griw, Ian C. Wood, Michael G. Salter(11-2017)

The present in vivo murine study was aimed to investigate the long-term effect of repeated administration of low-dose of the environmental toxicant trichloroethane (TCE) over three weeks on the spleen and peripheral blood cells, and the possible role of oxidative stress in TCE-induced toxicity. The results showed neither adverse clinical signs nor mortality on the TCE-treated mice. However, significant changes were noticed in the spleen of those animals. Grossly, the spleen of TCE-treated group was congested and enlarged (splenomegaly). Histpathologically, the splenic tissues of TCE-treated mice showed signs of toxicity as highly activated germinal centers of the white pulp with minimal apoptotic reaction as well as a prominent megakarocytosis and infiltration of the red pulp by comparatively increased number of eosinophiIs and mature lymphocytes were detected. In addition, lymphocyte numbers were decreased in peripheral blood as well as basophils. In contrast, there was an increase in monocyte numbers in the peripheral circulation. In addition, lipid peroxidation/ malondialdehyde formation, a biomarker of oxidative stress, was significantly induced by TCE treatment in the sera and spleen of mice, suggesting an overall increase in oxidative stress. These results provide further support to a role of oxidative stress in TCE-induced cell death, which could result in an impaired spleen function. This study concludes that attenuation of TCE-induced splenic damage in mice provides an approach for preventive and/or therapeutic strategies
Massaud S. Maamar, Mohamed A. Al-Griw, Rabia O. Al-Ghazeer, Seham A. Al-Azreg, Naser M. Salama, Emad M. Bennour(3-2016)

Exposure to chemicals has been shown to adversely affect CNS health in rodents and humans. The objective was to evaluate, in-vivo, the effects of trichloroethane (TCE), a ubiquitous environmental contaminant, on the integrity of neural cells. A group of albino mice was injected intraperitoneally twice weekly for three weeks with TCE (100 and 400 µg/kg). Animals were followed up for signs of toxicity and death. Alterations in neural tissues have also been investigated by histopathology The results showed a large number of degenerative neural cells (pyknosis of nuclei, DNA fragmentation, chromatin condensation) in the 100 and 400 µg/kg TCE-treated groups comparing to controls. Although there were no significant effect on the neural cell counts, the pattern of increased degenerative cells in TCE-treated groups was higher compared to controls. The results also showed that TCE led to a significant increase in the percent of degenerative neurons. There was also a significant reduction in the percent of neurons. These results correlated with the increase in the percent of glia. This study indicates that TCE exposure had detrimental impact on neural cells, and that neurons are more vulnerable to TCE than glia in this in-vivo mouse model.
Mohamed A. Al-Griw, Naser M. Salama, Soad A. Treesh, Lubna N. Algadi, Abdul hakim Elnfati(7-2015)

Evidence based medicine, clinical reasoning, self-directed critical thinking and problem solving approach are mandatory in order to acquire better retained and usable knowledge in a clinical context through student-centered teaching, and team interpersonal skills promotion. Adoption of new and high standards methods of teaching such as 3D models [24,25], along with updated responsive teaching materials are mandatory and represent pre-requirements for accredited medical schools
Aisha Nasef, Mohamed A Al-Griw, Adel El Taguri(5-2020)

Aim– This paper aims to review the existing literature relevant to the subject of ISO/IEC 17025 within Arabic countries and Libyan Research Centres Laboratories (LRCL), especially to the Critical Success Factors (CSFs) that effect the implementation of ISO/IEC 17025 standards. Therefore, a review of the literature revealed a major gap in studies in this area of quality standards for testing and calibration laboratories. Methodology– The aspects listed were based on a review of the literature. This paper summaries the key findings result within LRCL using SWOT and Template analysis to analyse the data collected from existing literature and LRCL data. Findings –The findings revealed that despite some organisations have faced challenges undertaking ISO/IEC 17025 implementations, many others have enjoyed the benefits that the systems have brought to the organisations. Outcomes of the research are important for Arabic and Libyan organisations implementing ISO/IEC 17025 systems and for consulting companies assisting with ISO/IEC 17025 implementation. The distribution of the current study results will lead to knowledge transfer and help organisations, among Arabic and developing countries including Libya, in the process of achieving standardisation. Originality, Value – The novelty of this research paper stems from the realisation of critical factors determining a successful implementation of ISO/IEC 17025 within research centers and Laboratories in Arabic countries and LRCL. The originality and value of this research paper is to fill the gap in knowledge in this area, which is explicit to the Arabic countries and Libya in particular. In addition, it contributes to the literature and professional practice by offering new insights into the CSFs for the implementation of ISO/IEC 17025 in Arabic countries and LRCL.
Anwar Salih Ali Al-mijrab, Maged Elmabruk Elgharib, Mohamed A. Al-Griw(5-2019)

Exposure to trichloroethane (TCE), an industrial solvent, has been shown to be negatively associated with reproductive performance. The present study was performed to assess the effects of TCE exposure on the reproductive performance and outcome in mice during a critical developmental window of later reproductive life. A group of female mice were injected intraperitoneally twice weekly for three weeks with TCE (100 and 400 µg/kg). Mice were followed up for signs of toxicity and death. Changes in uterine tissues have also been investigated by histopathology. The results showed that TCE exposure has reduced the number of F0 fertile females comparing to controls. Moreover, TCE exposure resulted in a decreased pups number and changed sex ratio in the litter of F0 TCE­treated dams. Histopathological examination revealed a TCE­induced uterine toxicity appeared as a severe endometrial hyperplasia with squamous cell metaplasia and adenomyosis. These results indicate that TCE exposure during a critical reproductive developmental window could affect the fertility and interfere with the reproductive outcome in mice.
Mohamed A. Al-Griw, Seham A. Azreg, Emad M. Bennour, Salem A. El-Mahgiubi, Ali R. Al-Attar, Naser M. Salama, Abdul Hakim Elnfati(10-2015)

تهدف هذه الورقة إلى التعرف على إدارة الجودة الشاملة، وتأثيرها في تحسين أداء مؤسسات التعليم العالي الليبي والعالم العربي، وبيان الانعكاسات الايجابية في الأداء نتيجة لتطبيق إدارة الجودة الشاملة المتمثلة في (التحسين المستمر، واعتماد الإدارة على المعلومات عند اتخاذ القارارت، ودعم الإدارة العليا لتطبيق إدارة الجودة الشاملة، وتركيز الجهود على تلبية حاجات ورغبات الزبائن). إذ توضح هذه الورقة أن إدارة الجودة الشاملة هي أسلوب إداري حديث متميز، ويتطلب من جميع الباحثين في المؤسسات التعليمية في ليبيا، رفع مستوي المنتج التعليمي من خرجين، وبحوث ودارسات، بما يتناسب مع متطلبات مجتمعاتها كما تهدف هذه الورقة لتوضيح مدى تحقيق جودة التعليم حيث ا عتمد ، العالي في المؤسسات التعليمية العربية والليبية من خلال منهج نظري وصفي يستعرض في هذه الورقة الباحثين في هذه الورقة على الأدبيات، والدارسات السابقة المتعلقة بهذا الموضوع، مفهوم إدارة الجودة الشاملة في التعليم العالي، ومميازته، ومتطلباته، ومعوقاته، والتحديات التي تواجه التعليم العالي في العالم العربي بما فيهم دولة ليبيا بالتحديد. كما تتجلي أهمية الدارسة من خلال تناولها لموضوع يتسم بالحداثة ويعد تطبيق المبادئ والأساليب الحديثة على مؤسسات التعليم العالي الليبي في غاية الأهمية، وذلك من أجل الارتقاء بها إلى معدلات عالية من الأداء والجودة ورفع كفاءة الخدمات المقدمة للطلبة والعاملين والباحثين وأعضاء هيئة التدريس. من خلال هذه الدارسة التي قام بها الباحثين تم استخلاص نتيجة مفادها ان تطبيق إدارة الجودة الشاملة يساهم في تعزيز القدارت التنافسية للمؤسسات وبالدرجة التي تمكنها من تحقيق أداء متميز لمواجهة حدة المنافسة التي يتميز بها عصرنا الحالي. وقد توصل الباحثين في هذه الورقة من خلال الدارسات السابقة لاقتارح عدد من التوصيات من أهمها: نشر ثقافة الجودة، الاهتمام بدعم البحث العلمي، دعم الإدارة العليا لتطبيق معايير وا جارءات اعتماد مؤسسات التعليم العالي الليبي الصادرة من المركز الوطني لضمان الجودة.
محمد عبدالسلام محمد القريو , , (12-2018)

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)

Maternal exposure to environmental chemicals can adversely affect fetal health. This study aims to identify, in-vivo, the risk of maternal exposure to trichloroethane (TCE) on the birth weight and the neurobehavioral performance of newborns. Groups of female albino mice (F0 generation) were injected intraperitoneally twice weekly for three weeks with TCE (100 and 400 µg/kg BW). Animals were followed up for signs of toxicity and mortality. Neonate's motor behavior including large movement (crawling, pivoting, righting) and small movement (tremor) were assessed. No toxicity adverse signs or mortality were observed in the animals (F0 generation) treated with TCE. The results showed that TCE exposure led to a significant increase in the F1 mouse body weight compared to controls. The results also showed that tremor of neonates of dams exposed to TCE (100µg/kg and 400µg/kg BW) were significantly increased when assessed on postnatal day-1 (PND-1). These findings provide support to a role of the environmental toxicant, TCE, in abnormalities in birth weight and neonatal neurobehavior.
Mohamed A. Al-Griw, Massaud S. Maamar, Naser M. Salama, Lubna N. Algadi, Abdul Hakim S. Elnfati, Emad M. Bennour(9-2015)

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)

Cellular elements of maturing brain are vulnerable to insults, which lead to neurodevelopmental defects. There are no established treatments at present. Here we examined the efficacy of selective adenosine A2A receptor inhibitor SCH58261 to combat brain injury, particularly oligodendrocyte (OL) lineage cells, in young rats. Wistar rats (n = 24, 6.5 days old) were randomly divided into equal groups of four. The sham (SHAM) group received no treatment, the vehicle (VEHICLE) group received 0.1% dimethylsufoxide, the injury (INJ) group was exposed to oxygen-glucose deprivation insult, and the injury+SCH58261 (INJ+SCH58261) group was exposed to the insult and received 1 μM SCH58261. Immunocytochemical experiments revealed that there was a significant reduction in the populations of mature OL (MBP+ OLs) and immature OL precursors (NG2+ OPCs) in the INJ group compared to SHAM group. Furthermore, there was also a significant increase in the percent of apoptotic MBP+ OL and NG2+ OPC populations as evidenced by TUNEL assay. In addition, there was a significant reduction in the proliferation rate among NG2+ OPCs, which was confirmed by BrdU immunostaining. On the other hand, treatment with SCH58261 significantly enhanced survival, evidenced by the reduction in apoptotic indices for both cell types, and it is preserved the NG2+ OPC proliferation. Activation of adenosine A2A receptors may contribute to OL lineage cell loss in association with decreased mitotic behavior of OPCs in neonatal brains upon injury. Future investigations assessing ability of SCH58261 to regenerate myelin will provide insights into its wider clinical relevance.
Mohamed A. Al-Griw, Rabia O. Alghazeer, Nuri Awayn, Ghalia Shamlan, Areej A. Eskandrani, Afnan M. Alnajeebi, Nouf A. Babteen, Wafa S. Alansari(1-2020)

Background: During early development, environmental compounds can induce adult onset diseases and disrupt the circulating vitamin D (VitD) levels. Aim: This study aimed to examine the protective role of VitD against the adverse effects of BPA on male and female mice. Methods: A total of 60 male and female Swiss Albino mice (3 weeks old) were randomly divided into 5 groups; each consisted of 12 mice (6 males and 6 females) and was treated as follows: Group I received no treatment (sham control); Group II, sterile corn oil only (vehicle control); Group III, BPA (400 μg/kg); Group IV, VitD (2,195 IU/kg); and Group V, BPA + VitD. At 10.5 weeks, the animals were sacrificed to conduct histological examinations. Results: BPA-exposed mice were found to have neurobehavioral abnormalities, heart, kidney, and lung diseases with increased apoptotic indices in both sexes. On the other hand, the treatment of BPA mice with VitD altered this scenario with modulated motor activity, enhanced body and organ weights, and preserved the heart, kidney, and lung architecture, alongside a decreased percent apoptotic index. Conclusion: Our findings illustrate that VitD protects mice against BPA-induced heart, kidney, and lung abnormalities. arabic 20 English 103
Mohamed A. Al-Griw(8-2021)

Bisphenol A (BPA), an endocrine and metabolic disruptor, is widely used to manufacture polycarbonate plastics and epoxy resins. Accumulating evidence suggests that paternal BPA exposure adversely affects male germlines and results in atypical reproductive phenotypes that might persist for generations to come. Our study investigated this exposure on testicular architecture and sperm quality in mouse offspring, and characterised underlying molecular mechanism(s). A total of 18 immature male Swiss albino mice (3.5 weeks old) were randomly divided into three groups and treated as follows: Group I, no treatment (sham control); Group II, sterile corn oil only (vehicle control); Group III, BPA (400 μg/kg) in sterile corn oil. At 9.5 weeks old, F0 males were mated with unexposed females. F0 offspring (F1 generation) were monitored for postnatal development for 10 weeks. At 11.5 weeks old, the animals were sacrificed to examine testicular architecture, sperm parameters, including DNA integrity, and oxidative stress biomarkers (malondialdehyde (MDA), protein carbonylation (PC), and nitric oxide (NO)). Results showed that BPA significantly induced changes in the body and testis weights of the F0 and F1 generation BPA lineages compared to F0 and F1 generation control lineages. A decrease in sperm count and motility with further, increased sperm abnormalities, no or few sperm DNA alterations and elevated levels of MDA, PC, and NO were recorded. Similar effects were found in BPA exposed F0 males, but were more pronounced in the F0 offspring. In addition, BPA caused alterations in the testicular architecture. These pathological changes extended transgenerationally to F1 generation males’ mice, but the pathological changes were more pronounced in the F1 generation. Our findings demonstrate that the biological and health BPA impacts do not end in paternal adults, but are passed on to offspring generations. Hence, the linkage of seen testis and sperm pathologies in the F1 generation to BPA exposure of their parental line was evident in this work. The findings also illustrate that oxidative stress appears to be a molecular component of the testis and sperm pathologies. arabic 18 English 101
Mohamed A. Al-Griw(11-2020)

Preterm infants have a high risk of neonatal white matter injury (WMI). WMI leads to reduced myelination, inflammation, and clinical neurodevelopmental deficits for which there are no effective treatments. Ionotropic glutamate receptor (iGluR) induced excitotoxicity contributes to oligodendrocyte (OL) lineage cell loss and demyelination in brain models of neonatal and adult WMI. Here, we hypothesized that simulated ischemia (oxygen‑glucose deprivation) damages white matter via activation of iGluR signaling, and that iGluR inhibition shortly after WMI could mitigate OL loss, enhance myelination, and suppress inflammation in an ex vivo cerebellar slice model of developing WMI. Inhibition of iGluR signaling by a combined block of AMPA and NMDA receptors, shortly after simulated ischemia, restored myelination, reduced apoptotic OLs, and enhanced OL precursor cell proliferation and maturation as well as upregulated expression of transcription factors regulating OL development and remyelination. Our findings demonstrate that iGluR inhibition post‑injury alleviates OL lineage cell loss and inflammation and promotes myelination upon developing WMI. The findings may help to develop therapeutic interventions for the WMI treatment.
Mohamed A. Al-Griw, Michael G. Salter, Ian C. Wood(1-2021)

ا كان لإلنسان أن يخطو، يف فترة وجيزة تقارب القرن من الزمن، هذه اخلطوات العمالقة يف مجال العلوم واملعرفة، بدون البحث العلمي الرصني الذي يعتمد الطريقة العلمية يف التفكير، وليس غريبا أن تكون إحدى أهم ركائز تصنيف اجلامعات العاملية مدى قدرة اجلامعة على اإلسهام الفاعل يف إثراء املعرفة االنسانية من خالل ما جتريه من بحوث. وانطالقا من اإلحساس مبسؤولياتها، ويف سبيل السعي إلى احلصول على موطأ قدم لها بني جامعات العالم، شكلت جامعة طرابلس جلنة من أساتذتها؛ لوضع مشروع وثيقة ألخالقيات البحث العلمي داخلها تلزم باحثيها اتباع االشتراطات، واملعايير، واملتطلبات األخالقية املنبثقة أس�اس�ا م�ن املفاهيم وامل�ب�ادئ العليا التي تقوم عليها املجتمعات، وتقرها الديانات واألعراف والتشريعات والثقافة واملواثيق الدولية ذات العالقة والتي تضبط وتنظم السلوك اإلنساني وتصنف املمارسات واألفعال والعالقات والسياسات، فيما إذا كانت مقبولة، أو غير مقبولة، ولتحافظ على أعلى مستوى ممكن من الشفافية واملصداقية يف العملية البحثية.
بسمة محمد خليفة دورو, خالد الهادي عبدالسلام الرفاعي, عبدالكريم امحمد احمد احتاش, محمد عبدالسلام محمد القريو , محمود احمد امحمد الديك, ضو خليفة محمد الترهوني, (1-2017)

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)

Background & aim: There is significant evidence indicating that endocrine disrupted bisphenol A (BPA) seriously endangers human health. In males, BPA affects testis architecture and sperm quality, and ultimately reduces fertility. This study explored the therapeutic potential of Nigella sativa (NS) seed extract on testis and sperm abnormalities in BPA-exposed mice and characterized the underlying mechanism. Methods: Forty male Swiss albino mice (5.5 weeks old, N = 8 per group) were randomly divided into five groups: Group I, normal control, Group II, vehicle control (sterile corn oil); Group III, NS-exposed (oral 200 mg/kg); Group IV, BPA-exposed (oral 400 μg/kg body weight); Group V, BPA + NS-exposed mice. Animals were treated for 6 weeks and sacrificed for biochemical and histological examination. Results: The results indicated that BPA exposure results in significant testis and sperm abnormalities. Specifically, BPA promoted a marked reduction in the body and testis compared with the control group. Histopathological findings showed that BPA caused a widespread degeneration of spermatogenic cells of the seminiferous epithelium, decreased sperm counts and motility, and augmented sperm abnormalities, and whereas little alteration to sperm DNA was observed. In addition, BPA increased the levels of the lipid peroxidation marker, malondialdehyde (MDA), and reduced the levels of the antioxidant marker, reduced glutathione (GSH). Treatment with NS oil extract during BPA exposure significantly alleviated testis and sperm abnormalities, reduced MDA levels, and enhanced GSH levels. Conclusions: The results demonstrate that NS oil protects mice against BPA-induced sperm and testis abnormalities, likely by suppressing levels of the oxidative stress marker, MDA, and enhancing the levels of the antioxidant marker, GSH.
Mohamed A M Al Griw (5-2022)

Accumulating evidence indicates the role of endocrine disruptor bisphenol A (BPA) in many pathological conditions. Histone deacetylase (HDAC) inhibition has potential for the treatment of many diseases/abnormalities. Using a mouse BPA exposure model, this study investigated the hepatoprotective effects of the Food and Drug Administration–approved HDAC2 inhibitor valproic acid (VPA) against BPA-induced liver pathology. We randomly divided 30 adult male Swiss albino mice (8 weeks old; N = 6) into five groups: group 1, no treatment (sham control (SC)); group 2, only oral sterile corn oil (vehicle control (VC)); group 3, 4 mg/kg/day of oral BPA (single dose (BPA group)); group 4, 0.4% oral VPA (VPA group); and group 5, oral BPA + VPA (BPA + VPA group). At the age of 10 weeks, the mice were euthanized for biochemical and histological examinations. BPA promoted a significant decrease in the body weight (BW), an increase in the liver weight, and a significant increase in the levels of liver damage markers aspartate aminotransferase and alanine aminotransferase in the BPA group compared to SC, as well as pathological changes in liver tissue. We also found an increase in the rate of apoptosis among hepatocytes. In addition, BPA significantly increased the levels of oxidative stress indices, malondialdehyde, and protein carbonylation but decreased the levels of reduced glutathione (GSH) in the BPA group compared to SC. In contrast, treatment with the HDAC2 inhibitor VPA significantly attenuated liver pathology, oxidative stress, and apoptosis and also enhanced GSH levels in VPA group and BPA + VPA group. The HDAC2 inhibitor VPA protects mice against BPA-induced liver pathology, likely by inhibiting oxidative stress and enhancing the levels of antioxidant-reduced GSH.
Mohamed A. Al-Griw, Zaynab Osama Alshibani, Rabia Omar abdullah Alghazeer, Mohamed Elhensheri, Refaat. M. Tabagh, Areej A. Eskandrani, Wafa S. Alansari, Mahmoud M. Habibulla, Ghalia Shamlan(6-2022)