Application of honeybee venom loaded nanoparticles for the treatment of chronic toxoplasmosis: parasitological, histopathological, and immunohistochemical studies.

Toxoplasma gondii is an opportunistic intracellular protozoon which may cause severe disease in the immunocompromised patients. Unfortunately, the majority of treatments on the market work against tachyzoites in the acute infection but can't affect tissue cysts in the chronic phase. So, this study aimed to evaluate the effect of bee venom (BV) loaded metal organic frameworks (MOFs) nanoparticles (NPs) for the treatment of chronic murine toxoplasmosis. Ninety laboratory Swiss Albino mice were divided into 9 groups (10 mice each); GI (negative control), GII (infected control), GIII-GXI (infected with Me49 strain of Toxoplasma and treated); GIII (MOFs-NPs), GIV and GV (BV alone and loaded on MOFs-NPs), GVI and GVII (spiramycin alone and loaded on MOFs-NPs), GVIII and GIX (ciprofloxacin alone and loaded on MOFs-NPs). Parasitological examination of brain cyst count, histopathological study of brain, retina, liver, and kidney tissue sections and immunohistochemical (IHC) evaluation of liver was performed. Counting of Toxoplasma brain cysts showed high statistically significant difference between the infected treated groups and GII. GV showed the least count of brain cysts; mean ± SD (281 ± 29.5). Histopathological examination revealed a marked ameliorative effect of BV administration when used alone or loaded MOFs-NPs. It significantly reduced tissue inflammation, degeneration, and fibrosis. IHC examination of liver sections revealed high density CD8+ infiltration in GII, low density CD8+ infiltration in GIII, GVI, GVII, GVIII, and GIX while GIV and GV showed intermediate density CD8+ infiltration. BV is a promising Apitherapy against chronic toxoplasmosis. This effect is markedly enhanced by MOFs-NPs.

Gallic acid and ferulic acid protect the liver from thioacetamide-induced fibrosis in rats via differential expression of miR-21, miR-30 and miR-200 and impact on TGF-ß1/Smad3 signaling.

This study evaluates the possible protective effects of gallic acid (GaA) and ferulic acid (FeA) against an experimentally induced liver fibrosis by thioacetamide (TAA) in rats. Animals were divided into: Control group, GaA group (20 mg/kg/day, p.o), FeA (20 mg/kg/day, p.o), TAA group (receiving 250 mg/kg twice/week, I.P), TAA + GaA group, TAA + FeA group (received the same previous doses) and TAA+silymarin group (received silymarin at 100 mg/kg/day+TAA as mentioned above). After 6 consecutive weeks, animals were sacrificed and the assessment of liver functions, oxidative stress biomarkers and histopathological examination of the liver tissues were performed. In addition, the effect on TGF-ß1/Smad3 signaling and the expression of miR-21, miR-30 and miR-200 were evaluated. The results showed that administration of GaA or FeA with TAA induced a significant reduction in serum ALT, AST and ALP activities and protected the integrity of liver tissues. Furthermore, they increased the activities of the hepatic antioxidant enzymes; superoxide dismutase and catalase while decreased malondialdehyde content to a normal level. The hepatic expression of TGF-ß1, phosphorylated and total Smad3 proteins were significantly decreased. In addition, miR-21 expression was downregulated while miR-30 and miR-200 expressions were upregulated by administration of gallic acid or ferulic acid. In conclusion, gallic and ferulic acids exhibit hepatoprotective and antioxidant effects against TAA-induced liver fibrosis in rats. These effects are mediated through inhibition of TGF-ß1/Smad3 signaling and differentially regulating the hepatic expression level of miR-21, miR-30 and miR-200.