The influence of ginger administration on cisplatin-induced cardiotoxicity in rat: Light and electron microscopic study

Abstract

Cisplatin is a powerful chemotherapeutic agent. Cardiotoxicity is one of its major adverse effects. Ginger is a commonly used element in herbal medicine due to its anti-oxidant potentials. This study was planned to assess the histological changes induced by cisplatin in the cardiac muscle and to clarify the possible protective influence of ginger intake. Forty rats were divided into four groups. Control; given normal saline. Ginger; received oral ginger (500 mg/kg/day) for 12 days. Cisplatin; given cisplatin (2 mg/kg/day) daily by intraperitoneal injection for 1 week. Cisplatin + Ginger; received ginger (500 mg/kg/day) for 5 days prior to and concomitant with intraperitoneal injection of cisplatin (2 mg/kg/day) for 1 week. Serum levels of lactate dehydrogenase (LDH) and creatine kinase (CK) were estimated. Cardiac specimens were subjected to light, electron microscopic and immunohistochemical study using anti-P53 and anti-TNF-α antibodies. Morphometric and statistical studies were done. In Cisplatin group, cardiac muscle fibers appeared disorganized, disrupted or degenerated with pyknotic nuclei and showed a significant rise in the number of anti-P53 positive nuclei. Significant increments in the percent area of collagenous fibers and TNF-α immune-expression were observed. Ultrastructurally, the cardiomyocytes displayed disorganized or interrupted myofibrils, swollen disrupted mitochondria, and widening of intercalated discs. Serum levels of CK and LDH were significantly elevated. Cisplatin + Ginger group showed marked improvement in the cardiac histology and ultrastructure, downregulation of P53 and TNF-α immune-expressions and reduction in CK and LDH serum levels. In conclusion, ginger exhibits a protective effect against cisplatin cardiotoxicity mostly through its anti-apoptotic, anti-oxidant and anti-inflammatory properties.