Development and validation of an analytical method by RP-HPLC for quantification of sibutramine hydrochloride in pharmaceutical capsules

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Acceleration of Sperm Transit Time and Reduction of Sperm Reserves in the Epididymis of Rats Exposed to Sibutramine

Sibutramine is a drug globally used for the treatment of obesity. The aim of this study was to investigate male reproductive disorders caused by sibutramine in adult rats. Wistar rats were treated for 28 consecutive days (gavage) with 10 mg/kg of sibutramine. Control animals received only vehicle (dimethylsulfoxide and saline). The rats were sacrificed for evaluation of body and reproductive organ weights, sperm parameters, hormone levels (luteinizing hormone, follicle-stimulating hormone, and testosterone), testicular and epididymal histopathology, sexual behavior, fertility and in vitro contractility of the epididymal duct. Sibutramine decreased (P < .05) weights of the epididymis and ventral prostate, but not of other reproductive organs. The sperm number and transit time in the epididymal cauda were decreased (P < .001), but the daily sperm production was not altered. Moreover, morphology and sperm motility, histopathology of the testes and epididymis, sexual behavior, fertility, and serum hormone levels were not altered by the treatment. Sibutramine increased the potency of norepinephrine and, per se, increased the mechanical activity of the epididymal duct in vitro. Thus, although sibutramine in these experimental conditions did not interfere with the reproductive process of rats, it provoked acceleration of the sperm transit time and a decrease in the sperm reserves in the epididymal cauda. This alteration is probably related to the sympathomimetic effect of this drug, as shown by the in vitro assays. In humans, use of this drug might present a threat for male fertility because sperm reserves in men are naturally lower than those in rats.

Multiple effects of sibutramine on ejaculation and on vas deferens and seminal vesicle contractility

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Sibutramine Effects on the Reproductive Performance of Pregnant Overweight and Non-Overweight rats

It is well established that sibutramine produces weight loss and is used frequently in women of childbearing age. However, the potential adverse consequences attributed to sibutramine use by women who may become pregnant is not known. It was thus of interest to determine the effects of sibutramine on the reproductive performance of pregnant rats. Overweight as well as non-overweight female Wistar rats were treated with sibutramine (6 mg/kg) orally, daily for 15 d and then mated with normal male rats. Pregnancy was confirmed and treatment continued with sibutramine until d 14 of pregnancy. on d 20 of pregnancy all rats were anesthetized for determination of various maternal and fetal parameters. There was a significant maternal weight reduction at the end of pregnancy in the non-overweight drug-treated group compared to the control (non-overweight, no drug). Sibutramine alone and overweight condition alone produced a significant increase in postimplantation loss and placental index. In the overweight with or without sibutramine groups a significant decrease in fetal weight was noted. Data suggest that sibutramine alone or the condition of excess weight in the absence of drugs produced impaired reproductive performance. However, treatment of overweight rats with sibutramine did not further exacerbate fetal loss compared to sibutramine alone or the effects noted with excess weight alone.

Slimmer or Fertile? Pharmacological Mechanisms Involved in Reduced Sperm Quality and Fertility in Rats Exposed to the Anorexigen Sibutramine

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeitos da sibutramina sobre o sistema reprodutor masculino de ratos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeitos do tratamento com sibutramina sobre a qualidade espermática de ratos machos Wistar

Pós-graduação em Biologia Geral e Aplicada - IBB

Efeitos da bupropiona sobre o comportamento sexual, parâmetros espermáticos e fertilidade de ratos machos e sobre a contratilidade do ducto epididimático in vitro

Pós-graduação em Biologia Geral e Aplicada - IBB

Avaliação dos efeitos promovidos pela sibutramina, associadas ou não à nicotina, nos tecidos reprodutivos de ratas albinas

Sibutramine is a drug recommended clinically for the treatment of obesity, but there are women that use the drug for maintenance of body weight. Many time this use occur associate to habit of tabagism, being the nicotine the main toxic compound in the cigarette. The goal of study was to evaluate the side effects promoted by sibutramine, associated or not to nicotine, in the reproductive tissue of adult female rats. Wistar animals (n = 30), were distributed in the groups: a) Control A (0.3 mL of distilled water; oral); b) Sibutramine (15 mg/kg of body weight; oral); c) Control B (0.3 mL of saline solution; intraperitoneal); d) Nicotine (4.0 mg/kg of body weight; intraperitoneal); e) sibutramine + nicotine. The treatments were conducted during 30 consecutive days (single dose, daily). Sibutramine, associated or not to nicotine, affected the folliculogenesis and luteogenesis. There were significant alterations (p<0.05) in the thickness of uterine layers, considerate each treatment. In conclusion, the administration isolated of sibutramine or nicotine promoted deleterious effects in the reproductive tissues of female rats and these effects were potential in the group that received both drugs.

Avaliação dos efeitos promovidos pela sibutramina, associada ou não à nicotina, nos tecidos reprodutivos de ratas albinas

Sibutramine is a drug recommended clinically for the treatment of obesity, but there are women that use the drug for maintenance of body weight. Many time this use occur associate to habit of tabagism, being the nicotine the main toxic compound in the cigarette. The goal of study was to evaluate the side effects promoted by sibutramine, associated or not to nicotine, in the reproductive tissue of adult female rats. Wistar animals (n =30), were distributed in the groups: a) Control A (0.3 mL of distilled water; oral); b) Sibutramine (15 mg/kg of body weight; oral); c) Control B (0.3 mL of saline solution; intraperitoneal); d) Nicotine (4.0 mg/kg of body weight; intraperitoneal); e) sibutramine + nicotine. The treatments were conducted during 30 consecutive days (single dose, daily). Sibutramine, associated or not to nicotine, affected the folliculogenesis and luteogenesis. There were significant alterations (p<0.05) in the thickness of uterine layers, considerate each treatment. In conclusion, the administration isolated of sibutramine or nicotine promoted deleterious effects in the reproductive tissues of female rats and these effects were potential in the group that received both drugs.

Bupropion treatment increases epididymal contractility and impairs sperm quality with no effects on the epididymal sperm transit time of male rats

Bupropion is a dopamine (DA) and norepinephrine (NE) reuptake inhibitor used as smoking cessation and antidepressant drug with a lower incidence of male sexual dysfunction. We showed previously that sibutramine, a norepinephrine/serotonine reuptake inhibitor, reduced male rat fertility. As there are no studies evaluating the impact of bupropion treatment on spermatic parameters and male fertility, we evaluated the effects of bupropion treatment (15 and 30 mg kg(-1), 30 days) on sexual behavior, spermatic parameters and fertility of male Wistar rats and on the epididymal duct in vitro contractility. Bupropion 15 mg kg(-1) increased the serum luteinizing hormone level and the epididymal duct contractility, but the sperm quality was not affected. At 30 mg kg(-1) bupropion impaired sperm quality increasing the incidence of non-progressive sperm. The male sexual behavior and fertility were not modified at both bupropion doses. These results, in rats, suggest the importance of studies evaluating the effects of bupropion on the human male sperm quality.