Effect of taurine supplementation on hyperhomocysteinemia and markers of oxidative stress in high fructose diet induced insulin resistance

<p>Abstract</p> <p>Background</p> <p>High intake of dietary fructose is accused of being responsible for the development of the insulin resistance (IR) syndrome. Concern has arisen because of the realization that fructose, at elevated concentrations, can promote metabolic changes that are potentially deleterious. Among these changes is IR which manifests as a decreased biological response to normal levels of plasma insulin.</p> <p>Methods</p> <p>Oral glucose tolerance tests (OGTT) were carried out, homeostasis model assessment of insulin resistance (HOMA) was calculated, homocysteine (Hcy), lipid concentrations and markers of oxidative stress were measured in male <it>Wistar </it>rats weighing 170-190 g. The rats were divided into four groups, kept on either control diet or high fructose diet (HFD), and simultaneously supplemented with 300 mg/kg/day taurine via intra-peritoneal (i.p.) route for 35 days.</p> <p>Results</p> <p>Fructose-fed rats showed significantly impaired glucose tolerance, impaired insulin sensitivity, hypertriglyceridemia, hypercholesterolemia, hyperhomocysteinemia (HHcy), lower total antioxidant capacity (TAC), lower paraoxonase (PON) activity, and higher nitric oxide metabolites (NOx) concentration, when compared to rats fed on control diet. Supplementing the fructose-fed rats with taurine has ameliorated the rise in HOMA by 56%, triglycerides (TGs) by 22.5%, total cholesterol (T-Chol) by 11%, and low density lipoprotein cholesterol (LDL-C) by 21.4%. Taurine also abolished any significant difference of TAC, PON activity and NOx concentration among treated and control groups. TAC positively correlated with PON in both rats fed on the HFD and those received taurine in addition to the HFD. Fructose-fed rats showed 34.7% increase in Hcy level. Taurine administration failed to prevent the observed HHcy in the current dosage and duration.</p> <p>Conclusion</p> <p>Our results indicate that HFD could induce IR which could further result in metabolic syndrome (MS), and that taurine has a protective role against the metabolic abnormalities induced by this diet model except for HHcy.</p

Bone Marrow Transplantation Restores Follicular Maturation and Steroid Hormones Production in a Mouse Model for Primary Ovarian Failure

Recent studies suggest that bone marrow stem cells (BMSCs) are promising grafts to treat a variety of diseases, including reproductive dysfunction. Primary ovarian failure is characterized by amenorrhea and infertility in a normal karyotype female, with an elevated serum level of follicle-stimulating hormone (FSH) and a decrease level of estrogen caused by a mutation in FSH receptor (FSHR) gene. Currently, there is no effective treatment for this condition. The phenotype of FSHR (−/−) mouse, FORKO (follitropin receptor knockout), is a suitable model to study ovarian failure in humans. Female FORKO mice have elevated FSH, decreased estrogen levels, are sterile because of the absence of folliculogenesis, and display thin uteri and small nonfunctional ovaries. In this study, we determined the effects of BMSC transplantation on reproductive physiology in this animal model. Twenty four hours post BMSC transplantation, treated animals showed detectable estroidogeneic changes in daily vaginal smear. Significant increase in total body weight and reproductive organs was observed in treated animals. Hemotoxylin and eosin (H&E) evaluation of the ovaries demonstrated significant increase in both the maturation and the total number of the follicles in treated animals. The FSH dropped to 40–50% and estrogen increased 4–5.5 times in the serum of treated animals compared to controls. The FSHR mRNA was detected in the ovaries of treated animals. Our results show that intravenously injected BMSCs were able to reach the ovaries of FORKO mice, differentiate and express FHSR gene, make FSHR responsive to FSH, resume estrogen hormone production, and restore folliculogenesis

Sodium selenite improves folliculogenesis in radiation-induced ovarian failure: a mechanistic approach.

Radiotherapy is a major factor contributing to female infertility by inducing premature ovarian failure (POF). Therefore, the need for an effective radioprotective agent is evident. The present study investigated the mechanism of potential radioprotective effect of sodium selenite on radiation-induced ovarian failure and whether sodium selenite can stimulate in-vivo follicular development in experimental rats. Immature female Sprague-Dawely rats were either exposed to gamma-radiation (3.2 Gy, LD(20)), once and/or treated with sodium selenite (0.5 mg/kg), once daily for one week before irradiation. Follicular and oocyte development, apoptotic markers, proliferation marker as well as oxidative stress markers were assessed 24-h after irradiation. In addition, fertility assessment was performed after female rats became completely mature at two months of age. Sodium selenite significantly enhanced follicular development as compared to the irradiated group. Sodium selenite significantly reversed the oxidative stress effects of radiation that was evidenced by increasing in lipid peroxide level and decreasing in glutathione level, and glutathione peroxidase (GPx) activity. Assessment of apoptosis and cell proliferation markers revealed that caspase 3 and cytochrome c expressions markedly-increased, whereas, PCNA expression markedly-decreased in the irradiated group; in contrast, sodium selenite treatment prevented these alterations. Histopathological examination further confirmed the radioprotective efficacy of sodium selenite and its in-vivo effect on ovarian follicles' maturation. In conclusion, sodium selenite showed a radioprotective effect and improved folliculogenesis through increasing ovarian granulosa cells proliferation, estradiol and FSH secretion, and GPx activity, whilst decreasing lipid peroxidation and oxidative stress, leading to inhibition of the apoptosis pathway through decreasing the expressions of caspase 3 and cytochrome c

Reproductive performance of control, irradiated and selenite treated females.

<p>Fecundability was expressed as a percentage of pregnant females among mated females. Fecundity was expressed as the number of pups per mated females. Fecundity values represent the median; they were compared by Kruskal-Wallis’s test followed by Dunn’s multiple comparisons as a post-hoc test, and differences were considered significant when P<0.05. a or b: Significantly different from control or radiation group, respectively at P<0.05.</p

Effect of sodium selenite (SS, 0.5 mg/kg, i.p.; once daily for 1 week) on oxidative stress markers in rats subjected to a single dose whole-body irradiation (3.2 Gy).

<p>Data expressed as Mean ± SD.</p><p>a or b: Significantly different from control or radiation group, respectively at P<0.05, using one-way ANOVA followed by Tukey–Kramer as a post-hoc test. Abbreviations: GSH, reduced glutathione; GPx, glutathione peroxidase; MDA, malondialdehyde.</p

Thymoquinone blocks lung injury and fibrosis by attenuating bleomycin-induced oxidative stress and activation of nuclear factor Kappa-B in rats

Pulmonary fibrosis is one of the most common chronic interstitial lung diseases with high mortality rate after diagnosis and limited successful treatment. The present study was designed to assess the potential antifibrotic effect of thymoquinone (TQ) and whether TQ can attenuate the severity of oxidative stress and inflammatory response during bleomycin-induced pulmonary fibrosis. Male Wister rats were treated intraperitoneally with either bleomycin (15 mg/kg, 3 times a week for 4 weeks) and/or thymoquinone (5 mg/kg/day, 1 week before and until the end of the experiment). Bleomycin significantly increased lung weight and the levels of Lactate dehydrogenase, total leucocytic count, total protein and mucin in bronchoalveolar lavage and these effects were significantly ameliorated by TQ treatment. As markers of oxidative stress, bleomycin caused a significant increase in the levels of lipid peroxides and nitric oxide accompanied with a significant decrease in the antioxidant enzyme activity of superoxide dismutase and glutathione transferase. TQ treatment restored these markers toward normal values. TQ also coun- teracted emphysema in air alveoli, inflammatory cell infiltration, lymphoid hyperplastic cells activation surrounding the bronchioles and the over expression of activated form of nuclear factor kappa-B (NF-B) in lung tissue that was induced by bleomycin. Fibrosis was assessed by measuring hydroxyproline content, which increased markedly in the bleomycin group and significantly reduced by concurrent treatment with TQ. Furthermore, histopathological examination confirmed the antifibrotic effect of TQ. Collectively these findings indicate that TQ has potential antifibrotic effect beside its antioxidant activity that could be through NF- B inhibition

Circulating hormone levels.

<p>Changes in serum levels of FSH (A) and Estradiol (B), expressed as a percentage of control, after sodium selenite administration in <i>γ</i>-radiation subjected rats. Values are given as mean ± SD. a or b: Statistically significant from control or radiation group, respectively at P<0.05 using one-way ANOVA followed by Tukey–Kramer as a post-hoc test.</p

Representative photomicrographs of hematoxylin and eosin-stained ovarian tissue sections.

<p>Histological sections of control (A and B) and sodium selenite (C and D) treated ovaries exhibit similar organization, with different stages of growing follicles (blue arrows). Compared with controls, <i>γ</i>-irradiated ovaries (E and F) have few, if any, resting oocytes in the cortex with severe hemorrhage (black arrow). Many oocytes in small primary follicles are degenerating in irradiated ovaries. (G and H) Sections taken from ovaries of rats exposed to <i>γ</i>-irradiation and pre-treated with sodium selenite show the apparent normal structure of the ovary, with multiple types of ovarian follicles. Scale bar, 10 <i>µ</i>m. GF: Graffian follicle, S: Stroma.</p

Effect of sodium selenite injection (SS, 0.5 mg/kg, i.p.; once daily for 1 week) and/or whole body-irradiation on ovarian and uterine weights.

<p>Data expressed as Mean ± SD.</p><p>a or b: Significantly different from control or radiation group, respectively at P<0.05 using one-way ANOVA followed by Tukey–Kramer as a post-hoc test.</p

Representative photomicrographs of hematoxylin and eosin-stained uterine tissue sections.

<p>(A) Section taken from uterus of control rat and (B) Section taken from the uterus of sodium selenite treated rat show normal mucosal lining epithelium (blue arrow) with multiple glands (black arrow). (C) Section taken from the uterus of rats subjected to <i>γ</i>-radiation shows high degeneration of the mucosal epithelium with vacuole appearance (red arrow). (D) Section taken from the uterus of rats subjected to <i>γ</i>-radiation and pre-treated with sodium selenite shows regeneration of the glandular and luminal epithelium with intact structure. Scale bar, 10 <i>µ</i>m. le: luminal epithelium, ge: glandular epithelium, S: stroma.</p