Thymoquinone protects against statin-induced cerebellar damage, apoptosis, and hepatic cytotoxicity in rats.

Statins are a class of drugs commonly prescribed to lower cholesterol and low-density lipoprotein (LDL) cholesterol levels, as well as to reduce morbidity and mortality associated with cardiovascular illnesses. However, statins are associated with potential side effects, such as muscle pain, liver problems, and neurological or psychiatric disturbances. Therefore, a protective medication is required to mitigate the harmful effects of statins. Thymoquinone (THQ), found in Nigella sativa, has several medicinal benefits and protective effects. The current study aimed to investigate the effects of simvastatin on cerebellar and hepatic tissues, focusing on cellular apoptosis, using light and electron microscopy, morphometric analysis, and immunohistochemical techniques. Additionally, the study evaluates whether thymoquinone can protect against simvastatin-induced histological and ultrastructural damage in hepatic and cerebellar tissues. Thirty adult male Wistar albino rats were divided into three equal groups. Group I was the control group (Ctrl group). Group II (statin group) received simvastatin (20 mg/kg/day) orally for 8 weeks. Group III (statin + THQ group) received concomitant treatment with simvastatin (20 mg/kg/day) and thymoquinone (10 mg/kg/day) for 8 weeks. Tissue specimens were taken from the liver and cerebellum of all animal groups and processed for light and electron microscopic examination. An immunohistochemical investigation for caspase-3 was performed. The molecular and granular layer thickness, number of Purkinje cells, central vein diameter, hepatocyte nuclear diameter, and optical density of anti-caspase-3-positive cells were measured in both the cerebellum and the liver in all experimental groups. Results showed that cerebellum from simvastatin-treated animals showed perinuclear halos in cells within the molecular layer. Purkinje cells appeared disorganized, irregularly arranged, shrunken, with irregular outlines, hyperchromatic nuclei, and vacuolated cytoplasm. Moreover, the granular cell layer appeared shrunken with irregular hyperchromatic nuclei. In addition, decreased thickness of both the molecular and granular layers, as well as a reduction in the number and diameter of Purkinje cells, was observed and confirmed by morphometric analysis. Liver tissue showed shrunken hepatocytes, widened blood sinusoids, widened central veins, and inflammatory cell infiltration. Furthermore, strong positive expression of caspase-3 was observed in both the cerebellum and liver. However, all these histological, ultrastructural, and morphometric changes were markedly decreased after the addition of thymoquinone. It can be concluded that simvastatin induces significant degeneration in both the cerebellar cortex and liver tissue, primarily due to increased oxidative stress and reduced antioxidant protection. Thymoquinone exerts protective effects against this oxidative damage in both organs and alleviates degenerative changes, suggesting that it may be recommended for hypercholesterolemic patients on statins.