Panicum gilvum, steroidal sapogenins and ovine crystal-associated cholangiohepatopathy

Abstract

AIMSThis study aimed to establish the aetiology and pathogenesis of ovine crystal-associated cholangiohepatopathy (CACH). Specifically, it sought to confirm that Panicum gilvum was hepatotoxic, that the steroidal sapogenin content of Panicum gilvum was responsible for its hepatoxicity, and to establish whether hepatobiliary porphyrin secretion was directly or indirectly blocked.SCOPEA general understanding of CACH was sought by specifically studying the kinetics of bile salt and bilirubin secretion in animals given Panicum gilvum or steroidal sapogenins. Hepatobiliary secretion was studied directly in sheep with exteriorised bile flow, and indirectly in sheep, cavies and rats by measuring plasma levels of bile salts and bilirubin. Hepatobiliary integrity and patency were assessed by light and electron microscopy. The steroidal sapogenin content of plants and livers was examined by thin-layer chromatography.Chapter 1 introduces CACH, steroidal sapogenins and reviews the literature on sheep, cavies and rats grazing steroidal sapogenin-yielding plants or given steroidal sapogenins.Chapter 2 provides details on the materials and methods used in the investigation.Chapter 3 reports the results of direct and indirect examinations of bile salt and bilirubin secretion in sheep fed Panicum gilvum for up to one month, and gives the sequence of hepatobiliary changes.Chapter 4 presents a comparison o f the steroidal sapogenin content of Panicum gilvum with the sapogenin content of livers from grazing sheep, and reports a lack of evidence for fungal cofactors.Chapter 5 reports the results of the direct examination of bile salt and bilirubin secretion in sheep infused with steroidal sapogenins or epismilagenin glucuronide.Chapter 6 reports the results of the indirect examination of bile salt and bilirubin secretion in cavies fed Panicum gilvum or steroidal sapogenins for up to one month, with descriptions of hepatobiliary structural changes and steroidal sapogenin content.Chapter 7 reports the results of the indirect examination of bile salt and bilirubin secretion in rats fed steroidal sapogenins for up to one month, and describes hepatobiliary structural changes and steroidal sapogenin content.CONCLUSIONS(1) Panicum gilvum can cause hepatobiliary failure in sheep and cavies.(2) Reduced bile salt secretion is the primary change in sheep grazing Panicum gilvum. The lack of sufficient bile salt micellar sinks for continuation of phylloerythrin secretion is probably responsible for the photosensitivity seen in affected sheep.(3) Steroidal sapogenins derived from plant saponins and absorbed from the gastrointestinal tract of grazing sheep are responsible for Panicum gilvum hepatotoxicity specifically and CACH generally.(4) Steroidal sapogenins block hepatocyte bile salt secretion biochemically, not physically by the occlusion of bile vessels with sapogenin glucuronide crystals.(5) Other agents that decrease bile salt secretion could act synergistically with steroidal sapogenins but are not necessary for the photosensitisation of sheep grazing steroidal sapogeninyielding plants.om/GIAG2.crl