Little is known about how liver fibrosis influences lobular zonation. To address this question, we used three mouse models of liver fibrosis, repeated CCl4 administration for 2, 6 and 12 months to induce pericentral damage, as well as bile duct ligation (21 days) and mdr2−/− mice to study periportal fibrosis. Analyses were performed by RNA-sequencing, immunostaining of zonated proteins and image analysis. RNA-sequencing demonstrated a significant enrichment of pericentral genes among genes downregulated by CCl4; vice versa, periportal genes were enriched among the upregulated genes. Immunostaining showed an almost complete loss of pericentral proteins, such as cytochrome P450 enzymes and glutamine synthetase, while periportal proteins, such as arginase 1 and CPS1 became expressed also in pericentral hepatocytes. This pattern of fibrosis-associated ‘periportalization’ was consistently observed in all three mouse models and led to complete resistance to hepatotoxic doses of acetaminophen (200 mg/kg). Characterization of the expression response identified the inflammatory pathways TGFβ, NFκB, TNFα, and transcription factors NFKb1, Stat1, Hif1a, Trp53, and Atf1 among those activated, while estrogen-associated pathways, Hnf4a and Hnf1a, were decreased. In conclusion, liver fibrosis leads to strong alterations of lobular zonation, where the pericentral region adopts periportal features. Beside adverse consequences, periportalization supports adaptation to repeated doses of hepatotoxic compounds.

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The present study was implemented to provide comprehensive information on the developmental sequence of the proventriculus of Muscovy ducks by gross examination, macro-micrometric analysis and by using light microscope, scanning electron microscope (SEM) and transmission electron microscope (TEM). Samples from 55 healthy post-hatching Muscovy ducks of both sexes ranging from 1 to 60 days old. The proventriculus began cranially opposite to the cranial end of the liver at 1-15 days old, but in front this level at 30 and 60 days old. Morphometrically, the length of the proventriculus was increased by about four folds while weight by 19 folds at 60 days old when compared with those at one day old. Scanning electron microscopy of the proventricular lumen at one day old exhibited numerous small mostly rounded irregularly distributed openings of the glands, but uniformly distributed and surrounded by closely packed concentrically arranged mucosal folds resembling a rosette shape at the older ages. Histologically, in all studied stages, rounded, elongated oval or polymorphic shaped lobules of the proventricular glands were occupied within the muscularis mucosa. The tubuloalveolar secretory units lined with secretory (oxyntico-peptic) cells with variable shapes had secretory granules increased by the development. Numerous argyrophilic endocrine cells were demonstrated away from the glandular lumen at older ages. Transmission electron microscopy revealed that the cytoplasm of the secretory cells contained homogeneously electron-dense granules at a young age, but two types of these granules could be recognized at 60 days old. In conclusion, this study provides a wide difference in the morphometric and the structure of the proventriculus from one day to 60 days old. This difference between the examined age-stages may be related to the feeding strategy (behavior) and the functional adaptations from the young to the older ages.

Varanus niloticus Ahmed et al. pyramidal and were localized in the surface epithelium of the esophagus and small intestine, and among the cells of the gastric glands. This is the first report about the histology of the alimentary tract of the Varanus niloticus. Further studies are required for investigation the possibility of using this animal as a model for studying the regulation of the digestive processes as well as to understand the theory of development.

The liver of reptiles is considered an important study model for the interaction between environment and hepatic tissue. Little is known about the histology of the liver of reptiles. The aim of the current study was to elucidate the histological architecture of the liver of the Nile monitor (Varanus niloticus). Liver fragments from the Nile monitor were collected in the summer season and processed for the light and electron microscopy. The liver of the Nile monitor was bi-lobed and the right lobe was found to be larger than the left lobe. Histological examination revealed indistinct lobulation of the liver, and the central vein, sinusoids and portal area were haphazardly organized. The hepatic parenchyma consisted of hepatocytes arranged in glandular-like alveoli or tubules separated by a network of twisted capillary sinusoids. The hepatocytes were polyhedral in shape with vacuolated cytoplasm and the nucleus was single rounded, eccentric, large and vesicular with a distinct nucleolus. The hepatocytes contained numerous lipid droplets, abundant glycogen granules and well-developed RER and mitochondria. The hepatocytes appeared to secrete into the bile canaliculi through the disintegration of their dark cytoplasm into the bile canaliculi. The space of Disse separating between the hepatocytes and sinusoids contained many recesses. The portal area contained branches of the portal vein, hepatic artery, bile duct and lymphatic vessels embedded in a connective tissue. Some non-parenchymal cells were described such as Kupffer cells, heterophils, melano-macrophages, intercalated cells, myofibroblasts in addition to the endothelium of the sinusoids. This is the first report about the histological structure of the liver of the Egyptian Nile monitor. The result presented here should be considered a baseline knowledge to compare with the pathological affections of the liver in this species.