The protective role of Diosmin, Hesperidine combination against heavy metals toxicity in Wistar albino rats: Biochemical, Immunohistochemical and Molecular Studies

Abstract

The benchmark of this study is to evaluate the antioxidant protective efficiency of Diosmin-Hesperidin combination, a natural citrus flavone of hesperidin derivative on heavy metals intoxication and Oxidative stress-induced damage in Wistar albino rats. Oral doses of diosmin-hesperidin in rats (200 and 100 mg/kg body weight, respectively) for a month (every other day) prior to heavy metals intoxication. Evaluation of the protective and antioxidant effects of the combination of diosmin and hesperidin, various Rt-PCR estimations, biochemical estimations, histopathological alterations as well as comet assay and caspase-3 activity for assessment of apoptosis were performed. Results indicated that heavy metals intoxication-induced decline in the levels of liver tissue P53 gene expression and increase of liver tissues of the apoptotic caspase-3 gene, also induced decline in the levels of liver tissue antioxidant parameters (SOD, GPx, and GSH), increased lipid peroxidation (MDA), DNA damage and apoptosis, these parameters were improved by pre-administration of diosmin+hesperidine. Diosmin+hesperidine dose (200 and100 mg/kg body wt. respectively) restored the p53 and caspase-3 genes near-normal values, antioxidant status to near normal and reduced lipid peroxidation, DNA, and tissue damage. These results were confirmed by histopathological examinations, which showed that pre-administration of diosmin+hesperidine protected the liver of albino rats against heavy metals intoxication-induced damage. Hence, it has been illustrated that diosmin+hesperidine might be an effective antioxidant and protector against heavy metals intoxication-induced damage in rats. Moreover, the diosmin+hesperidine alone pretreated group did not show any biochemical alterations, fold change of P53 or caspase-3 genes or DNA damage indicating the protective nature of the drug.

Optimization of Lipid Nanoparticles by Response Surface Methodology to Improve the Ocular Delivery of Diosmin: Characterization and In-Vitro Anti-Inflammatory Assessment

“…Pharmaceutics 2022, 14,1961 17 of 25 dosage. D-NLC formulations at 80 µ M and 160 µ M were therefore prepared and optimized (Table 5).…”

“…Inflammation and oxidative stress play an important role in the pathogenesis of many retinal degenerative diseases, such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). In such diseases, the control of the main homeostatic mechanisms that in normal conditions counteract the relevant production of reactive oxygen species (ROS), Pharmaceutics 2022, 14,1961 2 of 24 the consequence of the continuous exposure to light stimuli, and visual signal transduction pathways are lost and stress is uncontrolled [1][2][3][4]. The lack of control leads to an imbalance between pro-and antioxidative signalling and leads to disproportionate oxidative stress, inflammation, dysregulated immune responses, and in some cases a potential impairment of the blood-retinal barrier (BBB) and tissue damage [1,5].…”

“…Diosmin (diosmetin 7-O-rutinoside) is a naturally occurring flavone glycoside that has proven useful in the treatment of inflammatory diseases. It is obtained by dehydrogenation of hesperidin, and is abundant in the pericarp of several citrus fruits, but it can also be found in Barosma betulina and Ruta graveolens, L., both belonging to the Rutaceae family [14]. It has been shown to improve vascular resistance to inflammatory processes, thus the reason behind its use for the treatment of several circulatory system illnesses [15].…”