Olanzapine treatment sometimes produces transient liver biochemistry abnormalities, and such drug-induced liver injuries are mainly monitored by measuring blood levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), whereas alpha-glutathione-S-transferase (α-GST) is not routinely measured in clinics, even though it can serve as an earlier and more specific biomarker of liver damage. Susceptibility to drug-induced liver injury can much depend on the gene polymorphisms regulating the activity of DNA detoxification and repair enzymes. The aim of this study was to evaluate which of the three liver enzymes - α-GST, ALT, and AST - is the most sensitive biomarker of olanzapine-induced liver injury and how their blood levels are affected by the GSTT1, GSTM1, GSTP1, and OGG1 gene polymorphisms in 30 olanzapine-treated patients. Contrary to our hypothesis, the increase in serum α-GST levels was not significantly greater than that of the transaminases. ALT turned out to be an earlier biomarker of liver injury than the other two enzymes. No significant association was found between gene polymorphisms and liver enzyme levels, save for GSTP1 Ile/Val + Val/Val and ALT, which points to this genotype as a risk factor for drug-induced liver injury. Future studies might help to identify the underlying mechanisms of transient liver enzyme increase associated with this genotype.
Liječenje olanzapinom može dovesti do prolaznih abnormalnosti u jetrenim biokemijskim nalazima i takva se lijekom prouzročena oštećenja jetre obično nadziru mjerenjem razina alanin aminotransferaze (ALT) i aspartat aminotransferaze (AST) u krvi, a alfa-glutation-S-transferaza (α-GST) ne mjeri se rutinski u klinici premda može poslužiti kao raniji i specifičniji biomarker oštećenja jetre. Osjetljivost jetre na lijekove može dosta ovisiti o polimorfizmu gena regulatora aktivnosti enzima uključenih u procese detoksifikacije i popravka DNA. Cilj je ovoga istraživanja bio ocijeniti koji je od triju jetrenih enzima – α-GST, ALT i AST – najosjetljiviji biomarker olanzapinom prouzročenog oštećenja jetre te kako polimorfizmi gena GSTT1, GSTM1, GSTP1 i OGG1 utječu na njihove razine u 30 bolesnika koji su primali taj lijek. Suprotno našoj hipotezi, povišenje serumskih razina α-GST-a nije bilo značajno više od povišenja razina transaminaza. ALT se pokazao ranijim biomarkerom oštećenja jetre od ostalih dvaju enzima. Osim toga, nismo otkrili značajnu povezanost između genskih polimorfizama i razina enzima, izuzev za povezanost genotipa GSTP1 Ile/Val + Val/Val s ALT-om, što upozorava na povećani rizik od lijekom prouzročenog oštećenja jetre u nositelja ovoga genotipa. Buduća bi istraživanja mogla pomoći u prepoznavanju mehanizama uslijed kojih dolazi do prolaznog povišenja razina ovog jetrenog enzima povezanoga s ovim genotipom.
Keywords: ALT; AST; drug-induced liver injury; lijekom prouzročeno oštećenje jetre; mental disorders; mentalni poremećaji; psihotropni lijekovi; psychotropic drugs; α-GST.
© 2024 Aylin Elkama et al., published by Sciendo.