Effect of l-carnitine supplementation on lead acetate-induced liver cell apoptosis and inflammation: role of caspase-3 and glycogen synthase kinase-3ß enzymes.

AIM: The study aimed at studying the hepatoprotective effect of l-carnitine against lead (Pb) acetate-induced hepatocellular injury, emphasizing the role of caspase-3 and glycogen synthase kinase-3ß in hepatocellular apoptosis and inflammation. MATERIALS AND METHODS: Male Wistar rats were used. The experimental approach involved estimation of the liver enzymes' serum levels. Oxidative and inflammatory biomarkers were measured in hepatic tissue homogenates. Paraffin-embedded hepatic sections were prepared for histopathology and immunohistochemistry. Quantitative determination of the phosphorylated glycogen synthase kinase-3 beta was performed. KEY FINDINGS: The serum showed a significant elevation in ALT, AST, and LDH; tissue homogenates showed significant elevation in lipid peroxide and inflammatory biomarkers with significant reduction in reduced glutathione in the Pb acetate-treated group. Co-administration of l-carnitine with Pb acetate produced significant reduction in liver enzymes with significant improvement in oxidant, antioxidant and inflammatory markers. Lead acetate treatment significantly reduced the phosphorylated glycogen synthase kinase-3 beta, while l-carnitine enhanced its phosphorylation. Histopathological examination showed inflammatory reaction around blood vessels with fatty degeneration in hepatocytes of the Pb acetate intoxicated group. l-Carnitine caused a decrease in hepatic damage with minimal vascular alterations in central vein. Caspase-3 expression in hepatocytes was decreased in Pb-treated group supplemented with l-carnitine. SIGNIFICANCE: Our study reveals that oxidative stress and inflammation participate in Pb acetate-induced hepatocellular injury. Glycogen synthase kinase-3ß and caspase-3 play role in Pb acetate-induced hepatic damage. l-Carnitine shows significant protective effects against hepatocellular apoptosis and inflammation induced by Pb acetate through antioxidant, anti-inflammatory and anti-apoptotic pathways in part mediated by GSK-3ß inhibition.

Vaginal suppositories of cumin seeds essential oil for treatment of vaginal candidiasis: Formulation, in vitro, in vivo, and clinical evaluation.

Fungal infections by resistant Candida species continue to be a significant health problem. Novel antifungal agents such as essential oils of cumin seeds (EOCS) are tested against vulvovaginal candidiasis (VVC). The aim of this study was to develop coated polyethylene glycol (PEG) vaginal suppositories containing EOCS for treatment of VVC. PEG suppositories containing EOCS were prepared ppearance, weight variation, drug content, hardness, dissolution time, release, stability and anticandida activity were evaluated. Biocompatibility of selected formulation was tested in female rabbits, followed by clinical evaluation. Coated suppositories showed complete release of the oil after 30 min, in vitro anti-candida activity, enhanced stability and sufficient safety on the vaginal tissues of rabbits. Clinical results showed significant lower rates of vaginal itching, discharge and dyspareunia combined with negative cultures in 70% of patients, revealing efficacy of EOCS-containing vaginal suppositories for treatment of VVC.