Acetaminophen (APAP) is a widely used analgesic and antipyretic drug, which is safe at therapeutic doses but can cause severe liver injury and even liver failure after overdoses. The mouse model of APAP hepatotoxicity recapitulates closely the human pathophysiology. As a result, this clinically relevant model is frequently used to study mechanisms of drug-induced liver injury and even more so to test potential therapeutic interventions. However, the complexity of the model requires a thorough understanding of the pathophysiology to obtain valid results and mechanistic information that is translatable to the clinic. However, many studies using this model are flawed, which jeopardizes the scientific and clinical relevance. The purpose of this review is to provide a framework of the model where mechanistically sound and clinically relevant data can be obtained. The discussion provides insight into the injury mechanisms and how to study it including the critical roles of drug metabolism, mitochondrial dysfunction, necrotic cell death, autophagy and the sterile inflammatory response. In addition, the most frequently made mistakes when using this model are discussed. Thus, considering these recommendations when studying APAP hepatotoxicity will facilitate the discovery of more clinically relevant interventions.

Alternaria causes pathogenic disease on various economically important crops having saprophytic to endophytic lifecycle. Pathogenic fungi of Alternaria species produce many primary and secondary metabolites (SMs). Alternaria species produce more than 70 mycotoxins. Several species of Alternaria produce various phytotoxins that are host-specific (HSTs) and non-host-specific (nHSTs). These toxins have various negative impacts on cell organelles including chloroplast, mitochondria, plasma membrane, nucleus, Golgi bodies, etc. Non-host-specific toxins such as tentoxin (TEN), Alternaric acid, alternariol (AOH), alternariol 9-monomethyl ether (AME), brefeldin A (dehydro-), Alternuene (ALT), Altertoxin-I, Altertoxin-II, Altertoxin-III, zinniol, tenuazonic acid (TeA), curvularin and alterotoxin (ATX) I, II, III are known toxins produced by Alternaria species. In other hand, Alternaria species produce numerous HSTs such as AK-, AF-, ACT-, AM-, AAL- and ACR-toxin, maculosin, destruxin A, B, etc. are host-specific and classified into different family groups. These mycotoxins are low molecular weight secondary metabolites with various chemical structures. All the HSTs have different mode of actions, biochemical reactions, and signaling mechanisms to causes diseases in the host plants. These HSTs have devastating effects on host plant tissues by affecting biochemical and genetic modifications. Host-specific mycotoxins such as AK-toxin, AF-toxin, and AC-toxin have the devastating effect on plants which causes DNA breakage, cytotoxic, apoptotic cell death, interrupting plant physiology by mitochondrial oxidative phosphorylation and affect membrane permeability. This article will elucidate an understanding of the disease mechanism caused by several Alternaria HSTs on host plants and also the pathways of the toxins and how they caused disease in plants.