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)

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)

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)