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.

The Effect of Selenium Nanoparticles versus Royal Jelly against Cisplatin-Induced Testicular Toxicity in Adult Male Albino Rats: A Light and Transmission Electron Microscopic Study.

Background and Aim: Cisplatin (Cis) is a highly effective chemotherapeutic agent. However, it produces severe testicular toxicity. It was reported that some antioxidants could overcome this toxicity. Selenium nanoparticles and royal jelly (RJ) were among these reported antioxidants. Therefore, this study was designed to compare these two antioxidants in protecting the testes against Cis-induced toxicity. Materials and Methods: This study was conducted on sixty healthy adult male albino rats (weight: 200-220 g) randomized into six groups, ten animals each. Group I (control), Group II (animals received intragastric Nano Selenium), Group III (animals received intragastric RJ), Group IV (animals received an IP injection of Cis 7 mg/kg), Group V (animals received intragastric Nano Selenium, and Cis injection), and Group VI (animals received intragastric RJ and Cis injection). After 10 days, the animals were sacrificed by cervical decapitation. The testes were weighted, and specimens from the left testis were processed for histological and immunohistochemical techniques, whereas specimens from the right testes were prepared for transmission electron microscopic examination. Results: Cis-treated animals had significantly reduced weight of their testes. Light microscopic examination revealed severe histopathological changes in the germinal epithelium and Leydig cells, confirmed with electron microscopic examination. There was a significant increase in the color area percentage of Caspase-3 immunostaining of the germinal epithelium and Leydig cells, compared to that of the control group. Group II and III were similar to control group. Both Groups V and VI revealed significant preservation compared to the Cis group. Conclusion: Selenium nanoparticles and RJ partially improved testis from Cis-induced toxicity, However, there was no significant difference between both groups.

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.

Diosmin Mitigates Cyclophosphamide Induced Premature Ovarian Insufficiency in Rat Model.

The current study was designed to investigate the protective role of diosmin against cyclophosphamide-induced premature ovarian insufficiency (POI). Female Swiss albino rats received a single intraperitoneal dose of cyclophosphamide (200 mg/kg) followed by 8 mg/kg/day for the next 15 consecutive days either alone or in combination with oral diosmin at 50 or 100 mg/kg. Histopathological examination of ovarian tissues, hormonal assays for follicle stimulating hormone (FSH), estradiol (E2), and anti-Mullerian hormone (AMH), assessment of the oxidative stress status, as well as measurement of the relative expression of miRNA-145 and its target genes [vascular endothelial growth factor B (VEGF-B) and regulator of cell cycle (RGC32)] were performed. Diosmin treatment ameliorated the levels of E2, AMH, and oxidative stress markers. Additionally, both low and high diosmin doses significantly reduced the histopathological alterations and nearly preserved the normal ovarian reserve. MiRNA-145 expression was upregulated after treatment with diosmin high dose. miRNA-145 target genes were over-expressed after both low and high diosmin administration. Based on our findings, diosmin has a dose-dependent protective effect against cyclophosphamide-induced ovarian toxicity in rats.

Protective potential of curcumin in L-NAME-induced hypertensive rat model: AT1R, mitochondrial DNA synergy.

BACKGROUND & OBJECTIVES: Hypertension can be induced by inhibiting nitric oxide synthesis with L-NAME, which also has a role in oxidative stress. Curcumin has strong antioxidant property. Our aim was to examine the possible preventive role of curcumin on renal dysfunction secondary to hypertension. MATERIAL & METHODS: Twenty-four adult male Albino rats were divided in four groups: normal (N); curcumin (C; received curcumin 100 mg/kg/day by oral gavage for 10 weeks); hypertensive (H; received L-NAME 40 mg/kg/day in their drinking water for 4 weeks); and hypertensive-curcumin (HC; received L-NAME and curcumin). Arterial blood pressure was evaluated non-invasively for 4 weeks. Rats were then sacrificed for assessment of oxidative stress (catalase, lipid peroxidase, reduced glutathione and superoxide dismutase), renal function and structure, and biomarkers of apoptosis (Bcl-2 and caspase-3). AT1R expression and renal mtDNA integrity were also assessed. RESULTS: Curcumin attenuated the effects of L-NAME on blood pressure and renal function. The renal histopathological changes observed in the L-NAME group were improved by curcumin administration. The expression of Bcl2 and caspase-3 was improved associated with downregulation of AT1R in curcumin treated groups. The antioxidant markers and mtDNA fragmentation show marked increase in hypertensive group which significantly decreased after curcumin treatment. CONCLUSION: Curcumin improved blood pressure elevation renal dysfunction. These improvements mediated through anti-oxidant capabilities and downregulation of AT1R favoring reduced apoptosis and preserved mitochondrial DNA.