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)

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)

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)