OBJECTIVES: We explored the possible preventive/therapeutic effects of orlistat (a medication prescribed for weight loss) on obesity-induced steroidogenesis and spermatogenesis decline.
MATERIALS AND METHODS: Twenty-four adult male Sprague Dawley rats weighing 250-300 g were randomized into four groups (n = 6/group), namely; normal control, high-fat diet, high-fat diet plus orlistat preventive group and high-fat diet plus orlistat treatment group. Orlistat (10 mg/kg/b.w./d suspended in distilled water) was either concurrently administered with high-fat diet for 12 weeks (high-fat diet plus orlistat preventive group) or administered from week 7-12 post- high-fat diet feeding (high-fat diet plus orlistat treatment group). Thereafter, serum, testes and epididymis were collected for analyses.
RESULTS: Obesity increased serum leptin and decreased adiponectin levels, decreased serum and intra-testicular levels of follicle stimulating hormone, luteinising hormone and testosterone, sperm count, motility, viability, normal morphology and epididymal antioxidants, but increased epididymal malondialdehyde level and sperm nDNA fragmentation. Testicular mRNA transcript levels of androgen receptor, luteinizing hormone receptor, steroidogenic acute regulatory protein, cytochrome P450 enzyme (CYP11A1), 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase were significantly decreased in the testes of the high-fat diet group. Further, the levels of steroidogenic acute regulatory protein protein and enzymatic activities of CYP11A1, 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase were also significantly decreased in the testes of the high-fat diet group. Treatment with orlistat significantly decreased leptin and increased adiponectin levels, improved sperm parameters, decreased sperm DNA fragmentation, increased the levels of steroidogenic hormones, proteins and associated genes in high-fat diet-induced obese male rats, with the preventive group (high-fat diet plus orlistat preventive group) having better results relative to the treatment group (high-fat diet plus orlistat treatment group).
DISCUSSION AND CONCLUSION: Orlistat attenuated impaired spermatogenesis and steroidogenesis decline by up-regulating steroidogenic genes. This may not be unconnected to its significant effect in lowering serum leptin levels, since the hormone is known to dampen fertility potential. Therefore, orlistat may improve fertility potential in overweight/obese men.
MATERIALS AND METHODS: Ovariectomized adult female rats were given testosterone (1 mg/kg/day) alone or in combination with flutamide or finasteride between days 6 to 8 of sex-steroid replacement treatment, which was considered the period of uterine receptivity. Ultramorphology of tight junctions was visualized by transmission electron microscopy while distribution and expression of claudin-4 and occludin were examined by immunofluorescence and real-time polymerase chain reaction respectively.
RESULTS: Administration of testosterone caused loss of tight junction complexity and down-regulated expression of claudin-4 and occludin in the uterus.
CONCLUSION: Decreased endometrial tight junction complexity and expression of claudin-4 and occludin in the uterus during receptivity period by testosterone may interfere with embryo attachment and subsequent implantation.
METHODS: The petroleum ether, chloroform and methanol extracts of F. deltoidea were prepared and subjected to standardization using preliminary phytochemical and HPLC analysis. Dose selection was made on the basis of acute oral toxicity study (50-5000 mg/kg b. w.) as per OECD guidelines. Diabetes mellitus was induced with streptozotocin and rats found diabetic were orally administered with the extract (250, 500 and 1000 mg/kg) for 14 days. Levels of blood glucose and insulin were measured in control as well as diabetic rats on 0, 7 and 14th day. In addition, glucose metabolism regulating gene expression was assessed using RT-PCR.
RESULTS: HPLC analysis revealed that the methanol extract is enriched with C-glycosylflavones particularly, vitexin and isovitexin. In oral glucose tolerance test, oral administration of the methanol extract increased the glucose tolerance. The methanol extract showed significant (P genes expression on one hand, and up-regulation of hepatic GK and PPARγ genes expression on the other hand. The extract caused an increased expression of GLUT-4 gene expression in skeletal muscles which leads to normalize the hyperglycemia. The extract also nullified the toxic effects of streptozitocin by blocking its entry into the islet β-cells through reducing the expression of GLUT-2 gene.
CONCLUSION: It can be concluded that, F. deltoidea could potentially inhibits the streptozitocin-induced hyperglycemia in rats. Further the herb can be utilized as useful remedy for alleviation of diabetes complications.