Medical Science
Volume 24, Issue 101, January - February, 2020
Metallothionein induction ameliorates cisplatin-induced hepatotoxicity: Molecular and Cellular Study
Shareefa A. Al Ghamdi1,2♦, Ahd Y. Al Zamil1, Maryam A. Al Ghamdi1,2, Huda F. Al Shaibi1, Fahad A.Al-Abbasi1
1Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
2Experimental Biochemistry Unit, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah, Saudi Arabia.
♦Corresponding author
Dr. Shareefa A. AlGhamdi
Department of Biochemistry, Faculty of Science, King Abdulaziz University; Email: saaalghamdi1@kau.edu.sa
ABSTRACT
Cisplatin is effective as a chemotherapy treatment, but its toxicity is one of the undesirable effects that limit cisplatin use in cancer
patients. The central hypothesis of this study was that cisplatin induces hepatotoxicity by increasing reactive oxygen species (ROS),
thus induction of one of the most effective antioxidants metallothionein (MT) within the cells can ameliorate the cytotoxicity induced by cisplatin. An in vitro model of hepatocytes, the cell line HepG2, were treated by different concentrations of cisplatin, which
induced a dose dependent significant reduction in cell viability. HepG2 cells were treated with zinc sulphate to induce
metallothionein. The MTT results showed enhanced cell viability in HepG2 cells pre-treated with zinc sulphate compared to cells
treated with cisplatin alone. Reactive oxygen species (ROS) levels were quantified and resulted in that the HepG2 cells treated with
cisplatin displayed a significant higher concentration of ROS than control cells, while cells preincubated with zinc followed by
cisplatin show a significant reduction in ROS production. Gene expression data showed a significant increase in the expression of
metallothionein 2A (MT2A) in HepG2 cells pretreated with zinc sulphate when compared to cells treated with cisplatin alone.
Treating cells with zinc generally produced a protective effect against cisplatin-induced hepatotoxicity. The protective effect of zinc
is associated with its antioxidant properties, as it acts as a metallothionein inducer.
Keywords: cisplatin, metallothionein, hepatotoxicity, ROS, drug toxicity, free radicals, MT2A, liver
Medical Science, 2020, 24(101), 290-300
