Table 3.
Potential pharmaceuticals for treatment or prophylaxis of DILI.
| Pharmaceutical | Tentative Mechanisms of Action in DILI | First Author |
|---|---|---|
| ● Anticoagulants | Antithrombotic property such as in HSOS | Li 2022 [92] |
| ● Antioxidants (general) | Antioxidants in general are chemicals with variable structures to help protect cells and subcellular organelles from oxidative injury caused by reactive oxygen species (ROS). | Ali 2020 [93] |
| ● Bicyclol | Bicyclol is a synthetic drug that attenuates oxidative stress and endotoxins, partially via modulated expression of cytokines. | Yao 2009 [94] |
| ● Cholestyramine | Cholestyramine used orally interrupts the enterohepatic circulation of bile acids. | Einarsson 1991 [95] |
| ● Clausenamide | (+)-Clausenamide (CLA), a phytochemical initially isolated from leaves of Clausena lansium (Lour.) Skeels, increases in its synthetic form the hepatic cytosolic GSH content via stimulation of the key limiting enzyme γ-glutamylcysteine synthetase activity. Nowadays seen as a potential inhibitor of liver injury triggered through ferroptosis, CLA may help in DILI cases. | Wu 2006 [96] |
| ● Glucocorticoids (GCs) | GCs suppress excessive inflammatory processes and immunological responses. | Ye 2022 [97] |
| ● Immuno- suppressants |
Immunosuppression of CD8+ T cell lobular and necrotic hepatitis | Corrigan 2019 [98] |
| ● Iron chelators | The iron chelator deferoxamine and the ferroptosis inhibitor ferrostatin-1 alleviate ferroptosis in experimental acute APAP liver injury by protecting mitochondria via inhibiting voltage-dependent anion channel 1 (VDAC1) oligomerization by restoring hepatic ceramide and cardiolipin content. | Niu 2022 [99] |
| ● L-carnitine | L-carnitine is an antioxidant with protective properties against lipid peroxidation, as evidenced by increased malondialdehyde concentrations due to oxidative stress in experimental APAP liver injury, whereby the positive effect can be attributed to an increase of hepatic GSH levels. | Yapar 2007 [100] |
| ● Magnesium isoglycyrrhizinate (MgIG) | MgIG is a phytochemical extracted from licorice roots and known for its antioxidant, anti-inflammatory, and antiapoptotic characteristics. It inhibits oxidative stress and reduces the activities of superoxide dismutase and catalase, as well as levels of proinflammatory cytokines such as IL-1β, IL-6, and TNF-α. It also modifies the gut-liver axis by improving the gut microbial composition and intestinal barrier function. | Liu 2021 [101] Xia 2022 [102] |
| ● N-acetylcysteine (NAC) | NAC is known for its strong antioxidant properties and its capacity to increase hepatic levels of glutathione, enabling some protection of liver injury by the reactive intermediate N-acetyl-p-benzo quinone imine (NAPQI) as the metabolite of APAP generated via CYP 2E1 and 1A2. | Ntamo 2021 [103] |
| ● Polyene phosphatidylcholine (PPC) | PPC is a major component of membrane phospholipids, extract from soy, and rich in polyunsaturated fatty acids (PUFA), such as linoleic, linolenic, and oleic acids. It helps repair damaged membranes of the hepatocytes and relieve necroinflammation. | Fan 2022 [104] |
| ● Probiotics | Probiotics such as Lactobacillus reuteri, Lactobacillus rhamnosus, Bifidobacterium adolescens, Bacillus cereus, Akkermansia mucinophilia, Sacchoromyces boullardii, and Lactobacillus casei help reshape the gut microbiota, reinforce gut barrier function, and modulate pathways to reduce cytokines and hepatic inflammation. | Chen 2021 [105] |
| ● S-Adenosyl-methionine (SAM) | SAM participates in cellular reactions like transmethylation, transsulfuration, and aminopropylation; is the principal methyl donor in methyltransferase reactions; and the precursor for glutathione synthesis. | Noureddin 2020 [106] |
| ● Silymarin | Silymarin is a phytochemical derived from the milk thistle, syn Silybum marianum, with polyphenols, flavonolignans, and flavonoids as its constituents. It inhibits ROS formation, functions as a scavenger of ROS once formed, increases the hepatic level of glutathione, decreases lipid peroxidation, stimulates the synthesis of proteins and phospholipids within the hepatocytes, and inhibits hepatic NF-κB activation. | Aghemo 2020 [107] |
| ● Ursodeoxycholic acid (UDCA) | UCDA protects cholangiocytes against cytotoxic actions of hydrophobic bile acids, stimulates hepatobiliary secretion through enhanced expression of several transporter proteins like ABCB1, MRP2, and BSEP, and protects hepatocytes against apoptotic actions of bile acids. | Paumgartner 2002 [108] Parra-Landázury 2021 [109] |