{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T16:26:08Z","timestamp":1764433568882,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T00:00:00Z","timestamp":1721088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"In Vitro Drug Safety and Biotechnology"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Herbal and complementary medicine are frequently integrated with conventional medicine. We aim to report a case of severe herbal-induced liver injury (HILI) due to chronic use of green tea and protein shake. We present both clinical and laboratory evidence implicating mitochondrial toxicity and an immune response leading to a hypersensitivity reaction to the products. We have recently treated a 39-year-old man with hepatotoxicity resulting from a combination of a green tea-containing powder and a branched-chain amino acid supplement that was commenced 2 months previously. The hepatotoxicity resolved by stopping the consumption of these products and no other cause was detected. We decided to perform a lymphocyte toxicity assay (LTA) to determine if there was laboratory support for this diagnosis. LTA (% toxicity) represents the response of the mitochondria to toxic injury. To determine the role of the proinflammatory and anti-inflammatory cytokines and chemokines in the patient\u2019s reaction, we measured the level of cytokines and chemokine in the media of growing cells, exposed to each product or to a combination of products. The increased cytokines and chemokines are presented as the x-fold elevations from the upper limit of normal (ULN) for matrix metalloproteinase (MMP) (pg\/mL \u00d7 1.5 ULN) and interleukin (IL)-1\u03b2 (pg\/mL \u00d7 1.8 ULN). Higher elevations were found for interferon (IFN)-\u03b2, IFN-\u03b3, IL-8, IL 13, IL-15 (pg\/mL \u00d7 2 ULN), regulated upon activation, normal T cell expressed and presumably secreted (RANTES) (pg\/mL \u00d7 2 ULN), and nuclear factor (NF\u03baB) (pg\/mL \u00d7 3 ULN). The highest increases were for vascular endothelial factor (VEGF) (pg\/mL \u00d7 10 ULN), tumor necrosis factor (TNF)-\u03b1, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (pg\/mL \u00d7 13 ULN). An examination of cellular markers showed the difference between programmed cell death (apoptosis) and cell death due to necrosis. In our case, cytokeratin\u2014ccK18 (M-30) U\/L was within the normal limits, suggesting that apoptosis was normal, while ccK8(M65) U\/L was elevated at 1.5 \u00d7 ULN. This result implies that upon the treatment of the patient\u2019s lymphocytes with the products, the mechanism of toxicity is necrosis. In susceptible individuals, the combination of protein and herbal tea produces mitochondrial toxicity and a strong T-lymphocyte-1 response, leading to HILI. There is a need of international reporting of adverse drug reactions by clinicians, laboratories, and pharmaceutical manufacturers to drug regulatory authorities. This requires internationally accepted standard definitions of reactions, as well as criteria for assessment.<\/jats:p>","DOI":"10.3390\/cimb46070448","type":"journal-article","created":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T16:55:36Z","timestamp":1721321736000},"page":"7548-7557","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Phytotherapy-Induced Hepatocytotoxicity: A Case Report"],"prefix":"10.3390","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1865-8313","authenticated-orcid":false,"given":"Stephen","family":"Malnick","sequence":"first","affiliation":[{"name":"Department of Internal Medicine C, Kaplan Medical Center, Hebrew University, Rehovot 76100, Israel"},{"name":"Institute of Gastroenterology and Liver Disease, Kaplan Medical Center, Rehovot 76100, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Abdullah","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine C, Kaplan Medical Center, Hebrew University, Rehovot 76100, Israel"},{"name":"Institute of Gastroenterology and Liver Disease, Kaplan Medical Center, Rehovot 76100, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaacov","family":"Maor","sequence":"additional","affiliation":[{"name":"Institute of Gastroenterology and Liver Disease, Kaplan Medical Center, Rehovot 76100, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4262-9080","authenticated-orcid":false,"given":"Manuela G.","family":"Neuman","sequence":"additional","affiliation":[{"name":"In Vitro Drug Safety and Biotechnology and Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON M5G OA3, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1353\/pbm.1968.0004","article-title":"The spectrum of hepatotoxicity","volume":"12","author":"Zimmerman","year":"1968","journal-title":"Perspect. 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