The ameliorative effect of cerium oxide nanoparticles on chlorpyrifos induced hepatotoxicity in a rat model: Biochemical, molecular and immunohistochemical study.

BACKGROUND: Chlorpyrifos (CPF) is a widely used insecticide that causes toxicity to living organisms through the production of free radicals. Cerium oxide nanoparticles (CeO2NPs) are a new antioxidant agent that has proved therapeutic effects. We evaluated the effect of CeO2NPs on CPF hepatotoxicity. METHODS: Forty rats were randomized into four groups. Group I: rats received 1 ml corn oil by gastric tube once daily and 0.5 ml PBS by intra-peritoneal injection twice a week for 4 weeks. Group II: received CeO2NPs 0.5 mg/kg in PBS by i.p. injection, twice weekly for four weeks. Group III: were treated with oral administration of CPF 13.5 mg/kg in corn oil daily for 4 weeks. Group IV: received CPF as in group III, then each animal received CeO2NPs twice weekly for four weeks as in group II. Twenty-four hours after the last dose, rats were anesthetized and sera were collected for liver enzymes assessment. Afterwards, rats were sacrificed, livers were excised, the right lobe of each liver was fixed for immunohistochemical studies, and the left lobe was homogenized for oxidative profile assessment and molecular analysis. RESULTS: CPF group showed significant increase in liver transaminases, disturbance of the oxidative profile with up-regulation of BAX expression and down-regulation in the Bcl-2, Gadd45 and NFE2L2. CPF caused severe histopathological liver damage as well as significant increase in anti-Caspase 3 and TNF immunostaining. The CeO2NPs treated group revealed significant improvement of all previous parameters. CONCLUSION: CeO2NPs could alleviate CPF hepatoxicity through decreasing expression of the inflammatory and apoptotic proteins and increasing the activity of antioxidant enzymes.

Therapeutic Effect of Stem Cells on Male Infertility in a Rat Model: Histological, Molecular, Biochemical, and Functional Study.

Methotrexate (MTX) is a folic acid antagonist, widely used as a chemotherapeutic and immunosuppressive drug, but it is toxic to reproductive systems. In recent years, the era of stem cell applications becomes a promising point as a possible therapeutic agent in male infertility. This study is aimed at evaluating the therapeutic effects of stem cells at histological, molecular, biochemical, and functional levels in a methotrexate-induced testicular damage model. Material and Methods. Thirty rats were divided randomly into three groups (ten rats each): group 1 (control): animals received an intraperitoneal injection of 2 ml phosphate-buffered saline per week for 4 weeks, group 2 (MTX-treated group): animals were intraperitoneally injected with methotrexate (8 mg/kg) once weekly for 4 weeks, and group 3 (ADMSC-treated group): methotrexate-treated animals received a single dose of 1 × 106 stem cells/rat at the 5th week. At the 8th week, blood samples were collected for hormonal analysis; then, animals were sacrificed. The testes were dissected; the right testis was stained with hematoxylin and eosin. Random sections were taken from group 3 and examined with a fluorescent microscope. The left testis was divided into two specimens: the first was used for an electron microscope and the second was homogenized for molecular and biochemical assessments. Results. Group 2 showed significant histological changes, decreased free testosterone level, decrease in stem cell factor expression, and dysfunction of the oxidation state. The results revealed significant improvement of these parameters. Conclusion. Transplantation of adipose tissue-derived stem cells (ADMSCs) can improve the testicular damage histologically and functionally in a rat model.

Protective effect of Rosuvastatin on Azithromycin induced cardiotoxicity in a rat model.

AIMS: Azithromycin is widely used broad spectrum antibiotic recently used in treatment protocol of COVID-19 for its antiviral and immunomodulatory effects combined with Hydroxychloroquine or alone. Rat models showed that Azithromycin produces oxidative stress, inflammation, and apoptosis of myocardial tissue. Rosuvastatin, a synthetic statin, can attenuate myocardial ischemia with antioxidant and antiapoptotic effects. This study aims to evaluate the probable protective effect of Rosuvastatin against Azithromycin induced cardiotoxicity. MAIN METHOD: Twenty adult male albino rats were divided randomly into four groups, five rats each control, Azithromycin, Rosuvastatin, and Azithromycin +Rosuvastatin groups. Azithromycin 30 mg/kg/day and Rosuvastatin 2 mg/kg/day were administrated for two weeks by an intragastric tube. Twenty-four hours after the last dose, rats were anesthetized and the following measures were carried out; Electrocardiogram, Blood samples for Biochemical analysis of lactate dehydrogenase (LDH), and creatine phosphokinase (CPK). The animals sacrificed, hearts excised, apical part processed for H&E, immunohistochemical staining, and examined by light microscope. The remaining parts of the heart were collected for assessment of Malondialdehyde (MDA) and Reduced Glutathione (GSH). KEY FINDINGS: The results revealed that Rosuvastatin significantly ameliorates ECG changes, biochemical, and Oxidative stress markers alterations of Azithromycin. Histological evaluation from Azithromycin group showed marked areas of degeneration, myofibers disorganization, inflammatory infiltrate, and hemorrhage. Immunohistochemical evaluation showed significant increase in both Caspase 3 and Tumor necrosis factor (TNF) immune stain. Rosuvastatin treated group showed restoration of the cardiac muscle fibers in H&E and Immunohistochemical results. SIGNIFICANCE: We concluded that Rosuvastatin significantly ameliorates the toxic changes of Azithromycin on the heart.

Protective effects of Citrus limonia oil against cisplatin-induced nephrotoxicity.

Cisplatin is broadly used in the treatment of malignancies. However, the high incidence of nephrotoxicity following cisplatin use deters its clinical utility. Former studies have shown that the essential oils, obtained from Citrus limonia demonstrated significant anti-inflammatory and antioxidant effects. The aim of the current work was to evaluate the protective effects of Citrus limonia oil against cisplatin-induced nephrotoxicity. Thirty-two adult male mice were divided into four groups, eight mice each. The control group received distilled water, and the second group received a single intraperitoneal injection of cisplatin (20 mg/kg), while the third and fourth groups received cisplatin plus Citrus limonia oil at 100 or 200 mg/kg for 10 days, respectively. GC-MS analysis showed that the major components in Citrus limonia oil were D-limonene, 5-methyl-pentadecane, (n)-menthol, 3,7-dimethyl-(E)-2,6-octadienal, 3,7-dimethyl-2,6-octadienal, and nonadecane. Biochemical analysis showed that cisplatin intoxication was associated with significantly increased (p < 0.05) serum levels of urea and creatine and pro-inflammatory cytokines, as well as augmented renal tissue oxidative stress. Light microscopic examination showed loss of renal architecture, atrophied glomeruli, interstitial hemorrhage, dilated cortical tubules with cast formation, and excessive collagen production. Electron microscopic examination revealed compressed and karyorrhectic endothelial nuclei with chromatin condensation in the glomeruli, accumulation of mesangial matrix, and obliteration of glomerular blood capillaries. Co-administration of Citrus limonia oil attenuated these effects in renal histopathological, morphometric, and ultrastructural examinations, frequently in a dose-dependent manner. In conclusion, Citrus limonia oil can ameliorate the toxic effect of cisplatin on mice kidneys, probably through its antioxidant and anti-inflammatory effects.

Influence of surface nano-roughness on osseointegration of zirconia implants in rabbit femur heads using selective infiltration etching technique.

This study evaluates osseous healing of selective infiltration-etched (SIE) zirconia implants compared to as-sintered zirconia and titanium implants. Twenty implants of each group were inserted in 40 adult New Zealand white male rabbits. After 4 and 6 weeks, bone blocks containing the implants were retrieved, sectioned, and processed to evaluate bone-implant contact (BIC) and peri-implant bone density. SIE zirconia implants had significantly higher BIC and marginally higher bone density. The results suggest that selective infiltration-etched zirconia implant surface may improve implant osseointegration.

Biomechanical and histomorphometric evaluation of osseointegration of fusion-sputtered zirconia implants.

PURPOSE: The aim of this study was to evaluate osseointegration of fusion-sputtered zirconia implants in comparison with sandblasted, acid-etched titanium implants in a biomechanical and histomorphometric study. MATERIALS AND METHODS: Sixty zirconia implants were manufactured using CAD/CAM. Half received fusion sputtering surface treatment through spraying the green body implants with a jet of zirconia suspension. Standard Ti implants of the same shape and dimensions served as control. Thirty adult New Zealand white male rabbits were used in this study. Each animal received one fusion-sputtered and one Ti implant in one femur site and control zirconia in the other, for a healing period of 4, 8, and 12 weeks. At each healing time, a removal torque (RTQ) test was used to assess implant stability, while histological and histometric analyses were used to evaluate osseointegration. RESULTS: Fusion-sputtered zirconia implants demonstrated a statistically higher mean RTQ than control zirconia. When compared to Ti, however, although still higher, the differences were not significant. Histomorphometric evaluation revealed significantly greater bone-implant contact for fusion-sputtered zirconia implants compared to Ti after 4 and 8 weeks of healing time; however, at 12 weeks, the difference did not reach statistical significance. There were no significant differences in the measured bone density between fusion-sputtered and Ti implants, although the difference was significant when compared to the control zirconia. CONCLUSION: Fusion-sputtered zirconia implants demonstrated a degree of osseointegration and interfacial biomechanical stability comparable to Ti implants.