Atorvastatin protects against cyclophosphamide-induced thyroid injury in rats via modulation of JNK/ ERK/ p38 MAPK signaling pathway

Cancer chemotherapy is associated with various tissue toxicities that limit its use. Cyclophosphamide (CYC) is one of the most commonly used antineoplastic and immunosuppressive agent. Thyroid dysfunction is a critical side effect of anticancer drugs. Atorvastatin (ATV) is antihyperlipedemic drug with different tissue protective activities. The aim of this study was to determine the potential protective effect of ATV against CYC-induced thyroid injury in rats.ATV was administered in the presence and absence of CYC. Thirty-two adult Wistar rats were randomly divided into four groups: control group, ATV group (20 mg/kg/day, p.o. for 14 day), CYC group (200 mg/kg, i.p. on day 9) and ATV/CYC group. Triiodothyronine (T3), thyroxine (T4), reduced glutathione (GSH), malondialdehyde (MDA), total nitrite/nitrate (NOx), p38 mitogen-activated protein kinase (P38MAPK), extracellular signal-regulated kinase (ERK) and c-Jun N-terminal Kinase (JNK) were measured. In addition, thyroid histopathology and caspase 3 immunohistochemistry were performed.CYC significantly increased thyroid MDA, NOx, P38MAPK, ERK and JNK with decrease in GSH, T3 and T4 levels. Histopathological features of thyroid lesions and increased caspase 3 immune expression were appeared. ATV significantly normalized distributed oxidative, inflammatory and apoptotic indicators, resulting in an improvement of histopathological features and reduction of caspase 3 immunoexpression.These findings suggest that ATV protects against CYC-induced thyroid injury by regulating the JNK/ERK/p38-MAPK signaling pathway.