Plant and Fungal Hepatotoxicities of Cattle in Australia, with a Focus on Minimally Understood Toxins

Abstract

Plant- and fungus-derived hepatotoxins are a major cause of disease and production losses in ruminants in Australia and around the world. Many are well studied and described in the literature; however, this is not the case for a number of hepatotoxicities with economic and animal welfare impacts, such as acute bovine liver disease (ABLD), brassica-associated liver disease (BALD) and Trema tomentosa, Argentipallium blandowskianum and Lythrum hyssopifolia toxicity. Additionally, significant overlap in the clinical presentation and pathology of these conditions can present a diagnostic challenge for veterinarians. This review summarizes the current and most recently published knowledge of common plant- and fungus-associated hepatotoxins affecting cattle in Australia, with a focus on the mechanisms of toxicity and distinguishing diagnostic features. Consolidation of the current understanding of hepatotoxic mechanisms in cattle provides insight into the potential mechanisms of lesser-known toxins, including cellular and subcellular targets and potential metabolic pathways. In the absence of specific etiological investigations, the study of epidemiological, clinical and pathological features of hepatotoxicity provides valuable insights into potential toxic mechanisms and is integral for the successful diagnosis and management of these conditions.

Punicalagin Protects against the Development of Methotrexate-Induced Hepatotoxicity in Mice via Activating Nrf2 Signaling and Decreasing Oxidative Stress, Inflammation, and Cell Death

“…This could be attributable to increased glutamate uptake by pericentral hepatocytes, which enhances MTX polyglutamate production by folylpolyglutamyl synthatase and boosts intracellular MTX accumulation [ 55 ]. Furthermore, since the pericentral area is the furthest zone from the arterial blood supply, it has relatively lower levels of oxygen and GSH, making it more vulnerable to hypoxia and oxidative damage [ 56 , 57 ]. PU pre-treatment, on the other hand, demonstrated a potent hepatoprotective effect against MTX-induced hepatotoxicity, as shown by reducing both serum markers and histopathological features of liver injury.…”

Clinical and pathologic features of acute bovine liver disease in Australia

“…This does not explain the rare megalocytosis and multinucleation, which may be the result of the longer-term effects of ABLD toxin, or may be confounded by the effects of other chronically ingested hepatotoxic agents, such as pyrrolizidine alkaloids or aflatoxin B1, which cannot be excluded. 5,17 More work is required to determine not only the etiologic agent, but also the full spectrum of lesions associated with disease.…”

“…5,20 In southern Australia, causes of acute hepatotoxicosis, including Xanthium strumarium , Cestrum parqui , acute pyrrolizidine alkaloidosis, acute lupinosis, Brassica- associated liver disease, and less commonly, punicalagin or amatoxin toxicosis, are excluded on the basis of histopathologic features. 17 Other causes of acute hepatotoxicosis, such as Lophotoma spp. (sawfly) larvae, Cycad spp., and Lantana camara , are excluded on the basis of histopathologic features and geographic distribution.…”

“…(sawfly) larvae, Cycad spp., and Lantana camara , are excluded on the basis of histopathologic features and geographic distribution. 5,17…”

Investigation of Weather Triggers Preceding Outbreaks of Acute Bovine Liver Disease in Australia

“…[3], amatoxin (Amanita sp., Galerina sp., Lepiota sp.) [4], and copper [5], usually from parenteral administration [2,6,7]. Thus, a diagnosis of ABLD relies on histologic assessment and thorough-onsite examination.…”