Modulatory effect of ginger on skeletal malformations, cell cycle, apoptosis and structural changes in the liver of rat fetuses prenatally exposed to labetalol

Abstract

Background: Drug-induced liver damage with clinical symptoms has been related to labetalol in a number of instances. In addition to having a wide range of anti-inflammatory and antioxidant qualities, ginger also includes biotrace that are crucial in the fight against disease and skeletal deformity. In this study, we hypothesized that prenatal supplementation of ginger (200 mg/kg) attenuates skeletal malformation and hepatotoxicity mediated by labetalol during the organogenesis period. The tested dams were divided into four groups: control, ginger (200 mg/kg), labetalol (300 mg/kg) and combined group (labetalol and ginger at the same doses). Results: The labetalol group showed various skeletal abnormalities represented by mandibular hypoplasia, costal separation and retardation in the ossification. Histological and ultrastructural examination of the fetal liver tissue revealed multiple pathological changes. DNA damage, G0/G1 cell cycle arrest and a high percentage of apoptosis were also detected in the fetal hepatocytes from labetalol groups through gel electrophoresis and flow cytometry using PI and annexin V/PI methods, respectively. Administration of ginger after labetalol caused an evident decrease in these skeletal malformations, structural changes, DNA damage, apoptosis and G0/G1 cell cycle arrest. Conclusions: It can be concluded that ginger has great potential in attenuating the skeletal malformation, structural changes and cyto-genotoxicity of fetal hepatocytes upon prenatal exposure to labetalol.