Infliximab modulates cisplatin-induced hepatotoxicity in rats

Abstract

Background: Cisplatin (Cis) is one of the most com-monly used antineoplastic drugs. It is used as chemo-therapy for many solid organ malignancies such as brain, neck, male and female urogenital, vesical and pulmonary cancers. Infliximab blocks tumor necrosis factor alpha (TNF-?). Several studies have reported that infliximab ameliorates cell damage by reducing cytokine levels.Aims: We aimed to investigate whether infliximab has a preventive effect against cisplatin-induced hepatotoxicity and whether it has a synergistic effect when combined with Cis.Study Design: Animal experimentation.Methods: Male Wistar albino rats were divided in three groups as follows: Cis group, infliximab + Cis (CIN) group and the control group. Each group com-prised 10 animals. Animals in the Cis group received an intraperitoneal single-dose injection of Cis (7 mg/kg). In the CIN group, a single dose of infliximab (7 mg/kg) was administered 72 h prior to the Cis injec-tion. After 72 h, a single dose of Cis (7 mg/kg) was administered. All rats were sacrificed five days after Cis injection Results: TNF-? levels in the Cis group were signifi- cantly higher (345.5±40.0 pg/mg protein) than those of the control (278.7±62.1 pg/mg protein, p=0.003) and CIN groups (239.0±64.2 pg/mg protein, p=0.013). The Cis group was found to have high carbonic anhy- drase (CA)-II and low carbamoyl phosphate synthe- tase-1 (CPS-1) levels. Aspartate transaminase (AST) and alanine transaminase (ALT) levels were lower in the CIN group as compared to the Cis group. Total histological damage was greater in the Cis group as compared to the control and CIN groups. Conclusion: Cis may lead to liver damage by increas- ing cytokine levels. It may increase oxidative stress- induced tissue damage by increasing carbonic anhy- drase II (CA-II) enzyme levels and decreasing CPS-1 enzyme levels. Infliximab decreases Cis-induced hepatic damage by blocking TNF-? and it may also protect against liver damage by regulating CPS-1 and CA-II enzyme levels