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.
METHODS: This study was a quasi-experimental with posttestonly control group design. Twenty-five adult male Swiss Webster mice were randomly divided into five groups: shamoperated group (SO), UUO-control day-7 (U7), UUO-control day-14 (U14), UUO-chlorogenic acid day-7 (UC7), and UUOchlorogenic acid day 14 (UC14). Myofibroblasts were identified by immunohistochemical staining of alphasmooth muscle actin (α-SMA) while collagen fibers were identified by Sirius Red staining. Both data were presented as area fraction. BMP-7 and HGF mRNA expressions were assessed by reverse transcription PCR (RT-PCR). Data were quantified using ImageJ software.
RESULTS: UUO-control groups (U7 and U14) showed higher α- SMA-immunopositive (6.52±1.33, 18.24±1.39 vs. 0.22±0.01; p<0.05) and Sirius Red-positive area fractions (6.61±0.8, 12.98±2.31 vs. 0.62±0.10; p<0.05), lower BMP-7 (1.02±0.47, 1.18±0.65 vs. 2.09±0.87; p<0.05) and HGF mRNA expressions (1.06±0.31, 0.89±0.14 vs. 1.88±0.81; p<0.05) compared to SO group. UUO-chlorogenic acid groups (UC7 and UC14) showed lower α-SMA-immunopositive (1.24±0.37, 4.58±0.61; p<0.05) and Sirius Red-positive area fractions (4.76±1.03, 3.72±0.54; p<0.05), higher BMP-7 (1.84±0.49, 2.19±0.43; p<0.05) and HGF (1.58±0.38; p>0.05, 1.84±0.42; p<0.05) mRNA expressions compared to UUO-control groups. UUOchlorogenic acid groups showed BMP-7 and HGF mRNA expressions that were not significantly different from the SO group.
CONCLUSION: Chlorogenic acid administration prevents kidney fibrosis in UUO mice model through modulating antifibrotic pathway.
METHODS: Cold pain responses, including pain threshold and pain tolerance, were measured using the cold-pressor test (CPT). DNA was extracted from whole blood and genotyped for ABCB1 polymorphisms, including c.1236C>T (rs1128503), c.2677G>T/A (rs2032582), and c.3435C>T (rs1045642), using the allelic discrimination real-time polymerase chain reaction.
RESULTS: A total of 152 participants were recruited in this observational study. Frequencies of mutated allele for c.1236C>T, c.2677G>T/A, and c.3435C>T polymorphisms were 56.6%, 49.7%, and 43.4%, respectively. Our results revealed an association of the CGC/CGC diplotype (c.1236C>T, c.2677G>T/A, and c.3435C>T) with cold pain sensitivity. Participants with the CGC/CGC diplotype had 90% and 72% higher cold pain thresholds (87.62 seconds vs. 46.19 seconds, P = 0.010) and cold pain tolerances (97.24 seconds vs. 56.54 seconds, P = 0.021), respectively, when compared with those without the diplotype.
CONCLUSION: The CGC/CGC diplotype of ABCB1 polymorphisms was associated with variability in cold pain threshold and pain tolerance in healthy males.