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Apoptotic bodies were identified by the presence of pyknotic nuclei and various stages of karyorrhexis and karyolysis. The total number of apoptotic bodies were counted in each field and normalized to the live cells. We observed that on treatment with Ex4, there was a significantly lower number of apoptotic bodies in the steatotic liver as compared to the nontreated steatotic mice undergoing IRI (6.9 �� 3.06 versus 25.3 �� 4.3; P lead to lower apoptosis as compared to nontreated MAPK lean IRI (1.5 �� 0.6 versus 6.0 �� 1.4; P Smad inhibitor in overall improvement in resilience of the liver to IRI, in particular in the steatotic liver. To verify that the effect of Ex4 on steatosis was indeed a direct action, we performed TUNEL assays in HuH7 cells that were made steatotic in vitro and exposed to a hypoxia chamber. As shown in Figures 3, C and F, there was a significantly lower number of TUNEL-positive cells in lean and steatotic hepatocytes exposed to Ex4 as compared to nontreated lean and steatotic cells (5.8 �� 0.29 versus 26.6 �� 2.2 in lean cells; P EPZ5676 concentration to the in vivo protective effect of Ex4 seen in our previous experiment in decreasing cell death in hepatocytes undergoing IRI. Although the reduction in apoptosis is seen in both lean and steatotic cells, it is several-fold higher in the steatotic hepatocytes. The effectiveness of Ex4 in normal and steatotic livers undergoing IRI broadens the potential of its clinical applicability. To assess the effect of Ex4 on lipid droplets, we examined liver histology by H&E staining. In steatotic mice undergoing IRI without Ex4, there was an increase in coalescence of fat droplets or lipid droplet ��fusion�� leading to macrovesicular steatosis (Figures 4, B and E), a striking difference from the predominantly microvesicular fat before IRI (Figures 4, A and D). In the Ex4 treated mice, this effect was ameliorated with a significant reduction in large fat droplets (Figures 4, C and F). To study these lipid droplets at a subcellular level, we performed electron microscopy.