The possible protective effect of N-acetyl-L-cysteine and folic acid in combination against aspartame-induced cerebral cortex neurotoxicity in adult male rats: a light and transmission electron microscopic study.

The purpose of this study is to investigate structural and ultrastructural alterations in the rat's brain cerebral cortex after aspartame (ASP) treatment and to evaluate the possible ameliorating role of N-acetyl-L-cysteine (NAC) and folic acid (FA). Forty adult rats were divided into four equal groups: Group I, received appropriate vehicle only and served as control. Group II, received oral doses of both NAC (600 mg/kg body weight (b.w.)) and FA (12 mg/kg b.w.) daily for 42 days. Group III, received oral doses of ASP (500 mg/kg b.w.) daily for 42 days. Group IV, received both NAC and FA, concurrently with ASP at the same doses, route and period of administration of the previous groups. Histological examination of the cerebral cortex of ASP-treated rats showed severe degenerative changes, especially in the nerve cells. Some of these cells appeared shrunken, irregular in shape, while the others appeared swollen and were surrounded by pericellular halos. Immunohistochemical and morphometric study of ASP-treated group revealed a weak B-cell lymphoma-2 (Bcl-2) immunoexpression in the cytoplasm of many cells, while intense positive immunoreaction for glial fibrillary acidic protein (GFAP) was observed in the cytoplasm and processes of astrocytes compared to control group with statistically significant difference (p < 0.001). Light microscopic results were confirmed by ultrastructural findings. However, NAC and FA in combination had an obvious protective effect against ASP-induced injury in the rat's cerebral cortex. In conclusion, these results suggested that NAC combined with FA can ameliorate the toxic effect of ASP on the rat's cerebral cortex.

Role of alpha-lipoic acid in ameliorating Cyclosporine A-induced pancreatic injury in albino rats: A structural, ultrastructural, and morphometric study.

The aim of this study was to investigate the effectiveness of alpha-lipoic acid (α-LA) against cyclosporine A (CsA)-induced pancreatic toxicity in rats. Thirty-two male albino rats were divided into four equal groups. Group I treated orally (per os, p.o.) with vehicles and served as control; Group II received α-LA (100 mg/kg b.w. /day, p.o.) for 21 days; Group III received CsA (25 mg/kg b.w./day, p.o.) for 21 days; and Group IV received α-LA 1 hr before oral treatment by CsA for 21 days. Histological examination of the pancreas of CsA-treated rats showed marked changes represented by wide interlobular septae that contained congested blood vessels, cytoplasmic vacuolation of some acinar cells, and distortion of the other cells. Most of the islets of Langerhans showed vacuolation, degenerative changes, and loss of uniform cellular distribution. Some of the islets appeared shrunken with few cells. In the CsA group, the immunohistochemical and morphometric study demonstrated a decrease in the number of insulin-secreting ß-cells and also a reduction in islet diameters, with statistically significant difference (p < 0.001 and p = 0.004), respectively, compared with the control group. Ultrastructure of the exocrine and endocrine pancreatic cells of the CsA-treated group confirmed the light microscopic observation and showed dilated rough endoplasmic reticulum, decreased zymogen and secretory granules, damaged mitochondria, and abnormal nuclei. However, α-LA administration simultaneously with CsA resulted in some sort of regression of the previously mentioned effects. CONCLUSION: α-LA attenuated CsA-induced structural and ultrastructural changes in pancreatic cells, which were nearly reverted to their normal structure.

Potential testicular toxicity of sodium nitrate in adult rats.

Nitrate is a common contaminant in groundwater aquifers. Current study aimed at evaluating the potential testicular toxicity of sodium nitrate in rats. Sodium nitrate was given orally to rats at doses of 50, 100 or 200 mg/kg/day for 60 consecutive days. Sperm count and motility, daily sperm production and testis weight were significantly decreased specially at high doses. Testicular activity of lactate dehydrogenase-X, glucose-6-phosphate dehydrogenase, and acid phosphatase were inhibited in a dose-related manner. Lipid peroxides and hydrogen peroxide production were significantly increased in all treated animals. This was accompanied by inhibition of testicular activities of superoxide dismutase and glutathione peroxidase. Fifty mg/kg of sodium nitrate did not significantly alter catalase or glutathione reductase activity. Glutathione was significantly decreased by sodium nitrate in a dose-related manner. The decrease in sperm count and motility and daily sperm production was confirmed by histopathological studies which indicated chromatolysis, pyknosis and necrosis in spermatocytes. In conclusion, subchronic exposure of rats to sodium nitrate results in testicular toxicity as evidenced by decreased sperm count and motility, daily sperm production and testis weight, inhibited activity of enzyme markers of spermatogenesis and induction of histopathological changes. These effects are attributed, at least partly, to testicular oxidative stress.