Reversible testicular toxicity of piperine on male albino rats

Abstract

Background:Piperine was widely used in traditional medicine for inducing sterility and abortion.Objective:To evaluate the effect of the piperine on testis of male albino ratsMaterials and Methods:Adult male rats were divided into four groups (n = 12). Group I (control): Rats were given vehicle p.o. i.e. 0.5% carboxymethyl cellulose in normal saline daily for 60 days, Group II (ED): Rats received piperine at a dose of 10 mg/kg body weight (b.w.) daily, Group III (E4D): Rats received piperine at a dose of 10 mg/kg b.w. on every 4th day, Group IV (E7D): Rats received piperine at a dose of 10 mg/kg b.w. on every 7th day. Half of the animals from each group were sacrificed after the treatment period (60 days), and the remaining were kept for drug-free withdrawal period (60 days) and then sacrificed.Results:Piperine significantly decreased the reproductive organ weights in groups ED and E4D. Piperine induced hormonal imbalance by altering the serum levels of follicle-stimulating hormone, luteinizing hormone, sex hormone binding globulin, serum, and testicular testosterone in groups ED and E4D. Furthermore, piperine decreased the activity of germ cell markers and Leydig cellular steroidogenic enzymes in the groups ED and E4D after 60 days. All the above-altered values returned to normal levels after withdrawal period. Histopathological findings also supported the above findings.Conclusion:From the above data, it can be concluded that piperine could be a good lead molecule for the development of reversible oral male contraceptive.SUMMARY Piperine was employed for the contraceptive purposes in traditional medicinePiperine significantly impaired the spermatogenesis by decreasing the testicular hormone synthesis in groups ED and E4DPiperine disrupted the testicular antioxidant system by promoting the ROS production and hydroxyl radical generation in rat testis in groups ED and E4DHistopathological evidence supported the disruption of spermatogenesis by piperineAll the effects of piperine after the treatment period (i.e. 60 days) were back to normal after the withdrawal period (i.e., after 120 days).

Plant-Derived Alkaloids: The Promising Disease-Modifying Agents for Inflammatory Bowel Disease

“…Hu et al (2015) further revealed that the anti-colitis effect of piperine is independent of PXR activation, evidencing by the anti-colitis effect of piperine can be reversed by tail vein injection of PXR small interfering RNA (siRNA). The relative safe characteristic of piperine have been clearly stated in the toxicologic experiments (Piyachaturawat et al, 1983; Chinta et al, 2017; Bastaki et al, 2018). In adult male mice the LD50 value of piperine on intravenous, intraperitoneal, intramuscular, intragastric and subcutaneous orally administration were 15.1, 43, 400, 330, and 200 mg/kg, respectively; In parallel, the LD50 value of piperine on intraperitoneal route in adult female mice and weanling male mice were 60 and 132 mg/kg, respectively.…”

Safety Aspects of the Use of Isolated Piperine Ingested as a Bolus

“…Serum testosterone levels were elevated and the FSH levels were lowered in both piperine groups [ 63 , 64 ]. In this regard, the findings in juvenile rats differ from those observed in older rats [ 59 , 62 ].…”

“…In young adult male rats that orally received 10 mg piperine/kg bw/day (suspended in normal saline containing 0.5% carboxymethyl cellulose) for 60 days, Chinta and co-workers observed a statistically significantly ( p < 0.05) reduced epididymal sperm count, sperm motility and sperm viability compared to the control group (the latter receiving the vehicle only), accompanied by histopathological changes in the testes and epididymides; statistically significantly increased serum gonadotropins (FSH, LH), with a reduced intra-testicular testosterone concentration; and statistically significantly reduced activity of anti-oxidant enzymes or other enzymes in the testes and epididymides (for details, see Table 1 ) [ 16 , 62 ]. Data on reproductive organ weights were also recorded in this study, but in one of the two publications dealing with this study, inconsistencies were noticed between the testes weights and calculated indexes or a coefficient based on testes and body weights [ 62 ]. For this reason, no further detailed information on the weights of the reproductive organs is provided here.…”

“…With piperine administration (10 mg/kg bw) every 7th day, the individual parameters that were mentioned in relation to the daily piperine administration showed changes in the same direction but the changes were considerably milder and no longer statistically significant (e.g., sperm count, testicular testosterone). Chinta and co-workers concluded from their data that piperine might be a good lead molecule for the development of a reversible oral male contraceptive [ 16 , 62 ]. Animals receiving piperine every day displayed decreased body weight of about 10% after 60 days of piperine administration, which was not statistically significant.…”

Diverged Effects of Piperine on Testicular Development: Stimulating Leydig Cell Development but Inhibiting Spermatogenesis in Rats

“…It has been shown previously that the initiation of rat spermatogenesis required FSH while the maintenance of the process did not ( Zirkin et al, 1994 ). Further evidence that PIP may affect spermatogenesis with different mechanisms during puberty and at adulthood comes from the fact that FSH level was actually increased in adult rats after 10 mg/kg PIP treatment ( Chinta et al, 2017 ).…”