Fetal programming by sodium saccharin and damage on male offspring reproductive

Male infertility is responsible for 20-70% of infertility in couples. We investigated the effects of fetal programming with sodium saccharin consumption in testis structure and function and in male offspring fertility. Feed intake and efficiency, organ and fat weight, quantification and expression of AR and PCNA proteins, sperm count and hormonal dosages were performed. Changes in consumption were found in the final weeks of the experiment. Decreases in the expression and quantification of AR and PCNA, tubular diameter and luminal volume, and increase in epithelial and interstitial relative volumes were observed. Lower sperm count and transit and lower estradiol concentration were also found. The consumption of sodium saccharin by the dams programmed the male offspring affecting the HPG axis with alterations in Sertoli cell proliferation, AR expression and quantification, and sperm count. We hypothesize that these changes may be due to the reduction of estradiol that caused the loosening of the tight junctions of the blood-testis-barrier (BTB), causing cell losses during spermatogenesis, also reflecting, under the decrease in tubular diameter with an increase in epithelial volume and consequent decrease in luminal volume. Sodium saccharin programming directly affected the reproductive parameters of male offspring and adult fertility.

Drinking Non-nutritive Sweetness Solution of Sodium Saccharin or Rebaudioside a for Guinea Pigs: Influence on Histologic Change and Expression of Sweet Taste Receptors in Testis and Epididymis

Saccharin sodium and rebaudioside A are extensively used as non-nutritive sweeteners (NNSs) in daily life. NNSs elicit a multitude of endocrine influences on animals, differing across species and chemically distinct sweeteners, whose exposure induce activation of sweet taste receptors in oral and extra-oral tissues with consequences of metabolic changes. To evaluate the influence of NNSs on histologic change and expression of sweet taste receptors in testis and epididymis of young male guinea pigs, thirty 4-week-old male guinea pigs with body weight 245.73 ± 6.02 g were randomly divided into five groups (n = 6) and received normal water (control group) and equivalent sweetness low dose or high dose of sodium saccharin (L-SS, 1.5 mM or H-SS, 7.5 mM) or rebaudioside A (L-RA, 0.5 mM or H-RA, 2.5 mM) solution for 28 consecutive days. The results showed that the relative testis weight in male guinea pig with age of 56 days represented no significant difference among all groups; in spite of heavier body weight in L-SS and H-RA, NNS contributes no significant influence on serum testosterone and estradiol level. Low-dose 0.5 mM rebaudioside A enhanced testicular and epididymal functions by elevating the expressions of taste receptor 1 subunit 2 (T1R2) and gustducin α-subunit (GNAT3), and high-dose 7.5 mM sodium saccharin exerted adverse morphologic influences on testis and epididymis with no effect on the expression of T1R2, taste receptor 1 subunit 2 (T1R3), and GNAT3. In conclusion, these findings suggest that a high dose of sodium saccharin has potential adverse biologic effects on the testes and epididymis, while rebaudioside A is a potential steroidogenic sweetener for enhancing reproductive functions.

Formulation and Evaluation of Oral dispersible Tablet of Paroxetine Hydrochloride

Orodispersible tablets (ODTs) is one such novel approach which helps to increase user acceptance by virtue of rapid disintegration, self-administration without water or chewing. ODTs are solid unit dosage forms like the conventional tablets containing super disintegrants, which help them to disintegrate and/or disperse rapidly in the mouth within few seconds. The orodispersible tablet of Paroxetine hydrochloride was prepared by using direct compression method and the tablet were formulated using various concentration of Kyron T-314 as disintegrating agent, PVP K-30 as binder, F melt Type C as diluent, Sodium Saccharin as sweetening agent, talc as lubricant and Aerosil as glidant respectively. All the batches were prepared according to Factorial design. The prepared tablets were evaluated for various parameters like hardness, dissolution, friability, weight variation, disintegration time. Batch F5 was found to be the best batch as the disintegration time is minimum (26seconds) and better drug release profile. Orodispersible tablets of Paroxetine Hydrochloride were successfully formulated by which first pass metabolism could be avoided and faster onset of action could be achieved.

Fast-dissolving Sublingual Nanofibers of Ondansetron Hydrochloride: Formulation, Physicochemical Characterization, and Clinical Evaluation on Post-cataract Surgery Patients

Objective: Ondansetron hydrochloride (OND) is an antiemetic agent belongs to the 5-HT3 receptor antagonist class administrated widely in relieving nausea and vomiting which is the most common complication occurred after surgery. This study aimed to design and evaluate the physicochemical along with clinical effects of fast-dissolving nanofiber (FDN) of OND administrated sublingually to enhance the bioavailability, effectiveness, and patient compliance compared to orally disintegrating tablets (ODT). Methods: Nanofibers were prepared by the electrospinning method, using polyvinyl alcohol and alpha-cyclodextrin as polymers and sodium saccharin as the sweetener. Physicochemical and mechanical characteristics of nanofibers were examined then the clinical evaluation was performed. Eighty patients volunteering for cataract surgery were randomly divided into two groups, one received FDN, and the other treated with ODT of OND after recovery and in case of relieving nausea. The severity of nausea was assessed using a visual analogue scale in the 6 and 24 h intervals after drug administration. The SPSS 25.0 statistical software and statistical tests were used to analyze the obtained data. Results: Nanofibers possessed a mean diameter of 159 ± 30 nm beside suitable physicochemical and mechanical characteristics. Statistical evaluations showed that both FDN and ODT formulations had an equal anti-emetic effect (P>0.05) on reducing the severity of nausea but the FDN formulation caused significantly higher levels of patients’ satisfaction (P<0.05) compared to the ODT. Conclusions: Although both formulations had an almost equal anti-emetic effect, due to the benefits of this novel formulation including rapid disintegration, the ODT can be replaced by FDN.

Immunomodulatory Effect of Sodium Saccharin and Potassium Acesulfame in BALB/C Mice in Short-Term Trials

Introduction: Sweeteners are molecules that give a sweet taste to a foodstuff. The question of the correct use of sweeteners is still being studied because the results of investigations are often contradictory. Objective: the current study aims at evaluating the risk of short-term immunotoxicity induced by sodium saccharin and potassium acesulfame in BALB/c mice. Methods: Animals are given low concentrations of sweeteners (0%, 0.5%, 1%, 2%) in drinking water for 90 days. During this period, a subcutaneous immunization is conducted. Blood is taken from the retro-orbital sinus and the animals are sacrificed by cervical dislocation. Weight measurements and histological studies have involved spleen, thymus, bladder and lungs. Levels of immunoglobulins are measured by reversed single radial immunodiffusion. Results: A significant rise in the consumption of sweeteners is found in the groups receiving doses of 1% and 2% (p<0.05). Organ weight is not affected in both sexes (p>0.05). Histology shows no tissue abnormality of thymus and lungs in groups consuming sweeteners. However, histological disturbances of the spleen are observed in mice that have received the dose of 2%. Histological study of bladder has revealed hyperplasia in the groups receiving 1% and 2% of sweeteners. Immunodiffusion assay shows no change in immunoglobulin levels in the groups consuming sweeteners (p>0.05). Conclusion: Sweeteners have adverse effects on the immune system in BALB/c mice and induce histological abnormalities in the spleen and bladder. Keywords: Sweeteners, Saccharin, Potassium Acesulfame, Immunotoxicity, Immunoglobulins, Reversed single Radial Immunodiffusion.