Influence of onabotulinumtoxin A on testes of the growing rat

Onabotulinumtoxin A (onabotA) is gaining wide medical use in children. However, little is known about its potential testicular effects. The present study was planned to investigate the influence of its injection on the maturing testicular structures in rats. Immature rats were injected in the peritesticular area by onabotA with three doses of (10, 20 and 40 U/kg) three times in a two-week interval. The effect of these injections on fertility indices (sperm parameters, semen quality and testosterone levels) was examined. In addition, levels of antisperm antibodies and several apoptosis parameters were investigated. DNA content in form of ploidy was compared to control group via flow cytometric analysis

Multimechanistic antifibrotic effect of biochanin a in rats: implications of proinflammatory and profibrogenic mediators.

Biochanin A (BCA) is an isoflavone found in red clover and peanuts. Recently, it drew much attention as a promising anticancer and antioxidant. Due to its diversity in pharmacological actions, we were encouraged to investigate its potential as an antifibrotic, elucidating the different molecular mechanisms involved.Rats were pretreated with BCA, then injected with carbon tetrachloride (CCl4) for 6 weeks. Changes in liver weight and histology were examined and levels of aspartate and alanine aminotransferases, cholesterol, triglycerides, alkaline phosphatase and total bilirubin measured. To assess hepatic efficiency, indocyanine green was injected and its clearance calculated and albumin, total proteins and insulin-like growth factor-1 expression were measured. Cytochrome P4502E1 activity, cytochrome P4501A1 expression, in addition to sulfotransferase1A1 expression were determined to deduce the effect of BCA on hepatic metabolism. As oxidative stress markers, lipid peroxides levels, reduced glutathione, superoxide dismutase and catalase activities, as well as the total antioxidant capacity, were assessed. Nitric oxide, inducible nitric oxide synthase and cyclooxygenase-2 were used as indicators of the inflammatory response. Signaling pathways involving tumor necrosis factor-alpha, nuclear factor-kappa B, transforming growth factor-beta1, matrix metalloproteinase-9 and alpha-smooth muscle actin were investigated accordingly. Extent of fibrosis was examined by Masson's stain and measuring hydroxyproline levels.BCA pretreatment significantly protected against the chronic damage of CCl4. Liver injury, oxidative stress, inflammation and fibrosis markers decreased, while hepatic efficiency improved.Our findings suggested that BCA administration protects against fibrotic complications, a property that can be contributed to the multimechanistic approach of the drug

Effect of BCA on hepatic metabolic capacity.

<p>(<b>A</b>) CYP2E1 activity levels; (<b>B</b>) CYP1A1 expression levels; (<b>C</b>) SULT1A1 relative quantitation (RQ) versus group mean plot. <i>a</i>: significantly different from control gp. <i>b</i>: significantly different from CCl₄ gp.</p

Histopathological findings followed by grading of liver damage.

<p>(x40) (<b>A</b>) control: normal histological structure of portal area and surrounding hepatocytes; (<b>B</b>) CCl₄: loss of architecture with severe ballooning degeneration (arrow1), necrosis (arrow2) and fatty changes (arrow3) accompanied with fibrosis; (<b>C</b>) BCA+CCl₄: much less damage than in CCl₄ gp (<b>D</b>) BCA alone: similar to control gp.</p

Effect of BCA on oxidative stress markers.

<p>n = 8.</p>*<p>p<0.05 compared to CCl₄ group.</p>**<p>p<0.01 compared to CCl₄ group.</p>***<p>p<0.001 compared to CCl₄ group.</p

Effect of BCA on hepatic synthetic capacity.

<p>n = 8.</p>*<p>p<0.05 compared to CCl₄ group.</p>**<p>p<0.01 compared to CCl₄ group.</p>***<p>p<0.001 compared to CCl₄ group.</p

Representative images of liver sections of different experiments.

<p>(<b>A–E</b>): Immunohistochemical detection of COX-2, iNOS, NF-κB, MMP-9 and α-SMA (x100). Control gp: minimal expression; CCl₄ gp: extensive expression; BCA+CCl₄ gp: less than CCl₄ gp; BCA gp: minimal expression. Image analysis was performed by examining 6 fields/slide. (<b>F</b>): Masson trichrome stain (x40). Control gp: shows absence of collagen fibers (stained blue) between hepatic lobules; CCl₄ gp: extensive fibers deposition with pseudolobules formation (bridging fibrosis); BCA+CCl₄ gp: less fibers than CCl₄ gp; BCA gp: absence of fibers. The bar chart represents levels of hydroxyproline expressed as µg/gm of wet tissue measured by Reddy’s method. <i>a</i>: significantly different from control gp. <i>b</i>: significantly different from CCl₄ gp.</p