Synergistic Cardiac Protection by Thymoquinone and Valproic Acid in Absence Epilepsy.

This study aimed to investigate the effects of thymoquinone (T) and valproic acid (VPA), alone and in combination, on cardiomyocyte damage induced by absence epilepsy (AE) in rats. Adult male Wistar rats (C, T) and Genetic Absence Epilepsy Rats from Strasbourg (GAERS; AE, AE+T, AE+V, AE+V+T) were assigned to six experimental groups. C and AE received solvent; T and AE+T received thymoquinone (10 mg/kg, o.g.); AE+V received VPA (200 mg/kg, i.p.); AE+V+T received both treatments for 8 days. Hearts were collected for histological (Masson's trichrome) and biochemical analyses. AE caused molecular changes in cardiomyocytes without fibrosis, decreasing total antioxidant status (TAS) (-8.7 %) and increasing total oxidant status (TOS) (+50.7 %), oxidative stress index (OSI) (+155.5 %), MDA (+50.8 %), caspase-8 (+43.8 %), cleaved caspase-3 (+73.5 %), NF-?B (+239.4 %), TNF-? (+141.2 %), IL-6 (+12.9 %). Compared with the AE group, T increased TAS (+48.2 %), IL-6 (+5.8 %) and reduced OSI (-36.7 %), caspase-8 (-16.0 %), cleaved caspase-3 (-37.5 %), TNF-? (-1.8 %). VPA increased TAS (+58.5 %), while reducing TOS (-15.7 %), OSI (-48.9 %), MDA (-31.9 %), IL-6 (-14.1 %), caspase-8 (-27.3 %), cleaved caspase-3 (-51.0 %), TNF-alpha (-8.9 %), and NF-kappaB (-28.5 %). The VPA+T combination further improved these alterations, decreasing TOS (-24.8 %), OSI (-54.5 %), MDA (-35.6 %), TNF-alpha (-16.3 %), caspase-8 (-27.7 %), cleaved caspase-3 (-47.1 %), NF-kappaB (-31.8 %) and IL-6 (-26.9 %) while increasing TAS (+59.8 %). Our study demonstrates that AE increases oxidative stress, apoptosis and inflammation in cardiac tissue. While T and VPA alone showed limited protective effects, their combined administration significantly attenuated cardiac damage, supporting this approach as a promising strategy for cardiac protection.