possible protective role of curcumin versus garlic in amiodarone-induced keratopathy in rats: light and electron microscopic study

ABSTRACT

Amiodarone is a highly effective antiarrhythmic drug. However, amiodarone-induced corneal keratopathy is one of the most common side effects in humans. Amiodarone toxicity is attributed to its metabolites, which induce a significant increase in inflammatory mediators and cytokine release as well as free-radical formation. To clarify the possible protective effect of the natural antioxidants curcumin versus garlic on amiodarone-induced keratopathy. This study was carried out on 40 male albino rats weighing 180-200 g. The rats were divided randomly into four main groups [10 rats each] group I included rats that were used as controls. The rats in group II received amiodarone [30 mg/kg/day] daily by a gavage for 6 weeks. The rats in groups III and IV received curcumin [100 mg/kg/day] and garlic [300 mg/kg/day], respectively, plus amiodarone. After 6 weeks, blood samples were collected for the determination of malondialdehyde and superoxide dismutase serum levels. Then, corneal specimens were rapidly taken from all rats and processed for both light and electron microscopic examination. Light microscopic examination of group II corneal sections showed that the majority of the basal and intermediate epithelial cell layers of the corneal epithelium showed a vacuolated cytoplasm with pyknotic nuclei. The substantia propria became thick and showed abundant collagen bundles, focal masses of disorganized irregularly arranged collagen, and neovascularization. The Descemet's endothelial cell layer appeared thick with focal areas of stratification. In addition, the mean corneal thickness in group II was significantly increased [P<0.05]. Ultrastructural examination showed shrunken irregular basal and intermediate epithelial cell layers with multiple cytoplasmic vacuoles, wide intercellular spaces, and partial loss of the desmosomal junction. The keratocytes and stratified Descemet's endothelial cells showed numerous cytoplasmic vacuoles, lysosomes, and lamellar bodies. Moreover, the mean serum level of malondialdehyde was significantly increased [P<0.05] and the mean serum level of superoxide dismutase was significantly decreased [P<0.05]. In the rats of group IV, garlic significantly attenuated the amiodarone-induced corneal changes and the biochemical alterations compared with curcumin [group III]. Garlic exerts a greater ameliorative effect on amiodarone-induced keratopathy over curcumin and it can be recommended as an adjuvant therapy with amiodarone in patients treated with this drug for a long time