ABSTRACT

We aimed to histopathologically and biochemically investigate the protective effects of silymarin (SLY) against cardiac injury induced by a high-dose isotretinoin (ISR) administration.

Thirty-two male Balb/c mice were divided into four groups: control, ISR, SLY, and co-treated (ISR+SLY) groups. For the histopathological analysis, all sections were stained with hematoxylin–eosin and Masson’s trichrome. The TUNEL detection kit was used for the detection of cardiac apoptosis. The oxidative stress markers, which included catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px), and glutathione reductase (GSH-red), and the glutathione S-transferase (GST) and lipid peroxidation markers, which included erythrocyte malondialdehyde (E-MDA) and plasma malondialdehyde (P-MDA), were biochemically determined. All statistical analyses were conducted with SPSS 18.0 (IBM, New York, USA) and GraphPad Prism Version 6.01 (USA). The Student’s t-test was applied to the parametric data for comprising among groups. The P-significance degree was evaluated as 95%.

Severe histopathological alterations were observed in cardiac tissue. The ISR group showed hemorrhage, necrosis, edema, and congestion in cardiac tissues. SLY did not improve ISR-induced histopathological changes (p>0.05). The highest number of apoptotic cells was detected in the ISR group. In the ISR+SLY group, SLY treatment reduced apoptosis (p≤0.05). Antioxidant enzyme activities (CAT, SOD, GSH-Px, GSH-Red, GSH, GST) were induced in ISR+SLY group (p=0.015, p>0.05, p=0.002, p=0.002, p=0,018, p=0.002; respectively). E-MDA (p=0.003) and P-MDA (p=0.005) levels significantly increased in the ISR group and decreased in the SLY group.

SLY increased antioxidant enzyme activities, prevented lipid peroxidation, and decreased apoptosis. SLY was found to be an antioxidant against ISR-induced cardiac oxidative damage.

Keywords: Isotretinoin, silymarin, heart, oxidative stress, apoptosis, histopathology