Response to Aghdassi et al., Letter to the editor “Genetic polymorphisms in the UDP-glucuronosyltransferase UGT1A7 gene in patients with acute liver failure after kava–kava consumption”

Hepatotoxicity Induced by “the 3Ks”: Kava, Kratom and Khat

“…No CYP2D6 decrease in activity was assessed because no poor metabolizer phenotype was detected for this enzyme. In reply [ 27 ] to the previously reported study, Stickel highlighted that caution is needed when claiming an association, having analyzed only a limited case series of four patients. Also cyclooxygenase-1 and 2 (COX-1 and COX-2) inhibition could be responsible for kava hepatotoxicity [ 137 ], since yangonin and dihydrokavain inhibit these enzymes at the concentration of 100 μg/mL.…”

“…The 738 and 773 sources initially found, with “Kava” and “ Piper methysticum ”, respectively, were selected in order to exclude papers not appropriate for the purpose of the review and duplicate sources. Only 74 papers [ 8 , 11 , 12 , 15 , 16 , 26 , 27 , 28 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 ,…”

“…As suggested by Lebot [ 25 ], major criteria for kava quality are: chemotype, total kavalactone content, preparation and dilution method, part of the plant used, and dry or fresh material use. According to Sorrentino et al [ 26 ], kava products are to be considered safe at the dosage of 100 mg/kg/day (even though this dosage corresponds to 10 times the recommended daily dose) and, according to pre-clinical, clinical and toxicological studies, do not cause toxicity [ 27 ]. The first cases of kava related hepatotoxicity were described by Strahl et al [ 28 ] in 1998; since then, more than 100 cases of severe liver injury following kava exposure have been suspected worldwide.…”

Proteome and transcriptome analysis revealed florfenicol via affected drug metabolism and lipid metabolism induce liver injury of broilers

“…It mainly exists in the liver and combines with the microparticle membrane to catalyze the glucuronide combination reaction in phase II reaction of liver biotransformation. Several studies have shown that genes UGT1A9 and UGT147 are significantly correlated with DILI ( Jiang et al., 2015 ; Stickel, 2015 ; Terelius, et al., 2016 ). In this study, FFC significantly promoted the expression of ugt2a1, indicating that FFC can affect the phase II response of drug metabolism in liver through ugt2a1, and then affect the function of liver.…”