B.S. Setty

Spermicidal potential of saponins isolated from Indian medicinal plants

Abstract Saponins isolated from sixteen Indian plants showed spermicidal activity in human semen in both the Spot and IPPF tests. Spermicidal activity was found to be associated with the β-amyrin C-28 carboxylic acid type of sapogenins linked to a particular sequence of sugar moieties.

Studies with sub-toxic doses of α-chlorohydrin in the male monkey (Macaca Mulatta)

Subtoxic doses of alpha-chlorohydrin (3-chloro-12 -propanediol or U-5897) 20 mg per kg twice daily were fed to 5 adult male rhesus monkeys and 30 mg per kg for 15 days to 4 others in an attempt to produce functional sterility. 4 out of the first 5 died of unknown cause in 7 15 and 32 days; all appeared anorexic and sedated. The remaining monkeys were killed after 6 weeks (group 1) or 15 days (group 2) and were examined for genital tract and pituitary weight and histology; pituitary gonadotropin (mouse bioassay); sperm counts sperm zinc and oxygen uptake (Warburg technique); epididymal alkaline phosphatase; lactic acid total lipids phospholipids phosphoryl glyceryl choline sodium and potassium; seminal vessicle fructose; and prostate acid phosphatase. The only significant changes were increased zinc-65 uptake (6500 and 9100 counts per 100 seconds per 100 million sperm in 2 controls and 10300 and 16700 in 2 treated monkeys); and oxygen consumption (mean 270.4 mcl per hour per 100 million sperm in 3 controls and mean 577.6 in 2 treated monkeys) by vasal spermatozoa.

Mechanism of action of some acrylophenones, quinolines and dithiocarbamate as potent, non-detergent spermicidal agents

Some suitably substituted acrylophenones, quinolines and dithiocarbamate were synthesized as new generation, non-detergent spermicides and were studied for their mechanism of action in comparison with various known spermicides belonging to several different classes of chemical compound. Nonoxynol-9, benzalkonium chloride, Sapindus saponins, verapamil, emetine and tartaric acid were used as reference molecules to study the effect of new spermicides on human sperm motility parameters (using computer-assisted semen analyzer), plasma membrane integrity, lipid peroxidation and defense system against reactive oxygen species (ROS). Results have indicated that sperm plasma membrane remains the primary site of action of most of the spermicides, though the effect may be predominantly on the physiological integrity rather than the structural integrity in case of the new compounds. Lipid peroxidation may play an important role in disrupting sperm membrane physiology that may or may not be accompanied with a detrimental effect on the defense system of the human spermatozoa against the ROS.

Morphological changes in human spermatozoa as examined under scanning electron microscope after in vitro exposure to saponins isolated from sapindus mukorossi

Saponins isolated from Sapindus mukorossi have potent spermicidal activity. Morphological changes in human ejaculated spermatozoa after exposure to these saponins were evaluated under Scanning Electron Microscope. The minimum effective concentration (0.05% in spot test) did not affect the surface topography after exposure for 1 minute. However, incubation of spermatozoa for 10 minutes resulted in extensive vesiculation and disruption of plasma membrane in the head region. Higher concentrations (0.1%, 1.25%, 2.5% and 5.0%) caused more or less similar changes which included vesiculation, vacuolation, disruption or erosion of membranes in the head region. These findings suggest that the morphological changes observed are due to alterations in the glycoproteins associated with the lipid bilayer of plasma membrane of spermatozoa.

Biological profile of 2-[4-(2-n-piperidinoethoxy) phenyl]-3-phenyl (2h) benzo (b) pyran — A potent antiimplantation agent in rat

Compound CDRI-85/287: 2-[4-(2-N-piperidinoethoxy) phenyl]-3-phenyl (2H) benzo (b) pyran has been identified as a potent antiimplantation agent in rat. A single oral dose (2.5 mg/kg body weight) of the compound administered on days 1, 2 or 3 of pregnancy or multiple dosing (0.05 mg/kg daily) on days 5-7 postcoitum effectively prevented pregnancy. When administered on days 5-7 postcoitum, it failed to interrupt pregnancy even at 20 mg/kg dose. The compound is a potent antiestrogen, with very weak uterotrophic activity; it does not induce vaginal cornification in immature ovariectomised rat. Also, it is devoid of progestational, antiprogestational, androgenic, antiandrogenic and antigonadotrophic activities. The results suggest that the compound exerts its antiimplantation acivity in rat by virtue of its antiestrogenic activity [corrected].

CDRI-85/287, A novel antiestrogen and antiimplantation agent: Biological profile and interaction with the estrogen receptors in immature rat uterus

Postcoital antifertility efficacy, estrogenic and antiestrogenic activities of compound 85/287 were determined by the subcutaneous route in rats. It was 100% effective in preventing implantation at 0.5 mg/kg dose when administered within 24 h of mating and at 0.05 mg/kg in the days 1-5 post-coitum regimen. In the immature rat bioassay, it exhibited mild uterotrophic effect at the contraceptive dose but when administered along with estradiol (E2), it caused almost complete inhibition of uterine weight gain and vaginal cornification at the 2 mg/kg dose. E2 administration to immature rats (0.1 microgram, s.c., 3 days) caused 3-5 fold increase in the nuclear as well as cytoplasmic estradiol receptor (ER) content as compared to controls. In contrast, 85/287 (0.5 mg/kg and 2 mg/kg; s.c.), only translocated the ER to the nuclear compartment resulting in a depletion of cytoplasmic ER levels. Concurrent administration of 85/287 and E2 inhibited E2-induced increase in cytoplasmic ER. It is suggested that compound 85/287 exerts its antiestrogenic and antiimplantation action by interfering with the formation of E2-receptor complexes in the uterus.

Studies on mechanism(s) of antifertility action of gossypol in rat and hamster

This study was undertaken with a view to investigate the possible mechanism(s) of antifertility action of gossypol acetate in rats and hamsters. Adult male rats were treated by gavage with 30 mg/kg/day of gossypol for 7 weeks and adult male hamsters were treated similarly with 20 mg/kg/day gossypol for 8 weeks. The treatment caused a marked reduction in the weights of testis and epididymis. Histological examination of the testis in the two species revealed presence of seminiferous tubules showing varying degrees of damage along with a large number of normal tubules. Exfoliation of germ cells and spermatogenic arrest at spermatid stage was a common feature. Leydig cells presented normal morphological features. Though there was a reduction in the diameter of epididymal tubules, the epithelium did not show any morphological alterations. Examination of vasal flushings revealed marked reduction in sperm population and consisted of decapitated and immotile spermatozoa. Gossypol caused a significant reduction in the levels of total protein, RNA and DNA, and a marginal decrease in glycogen content in the testis. This was accompanied by a reduction in the activities of SDH and MDH. Except for LDH activity which showed a marked rise, there was no effect on glycolytic enzymes in the testis. The concentrations of glycerylphosphorylcholine and sialic acid were reduced in the cauda epididymis. The antifertility effects of gossypol appear to be due to its action both on testis as well as on epididymis.

Biological properties of 2-phenyl-3-p-(β-pyrrolidinoethoxy)-phenyl-(2:1,b) naphthofuran — A new oral antifertility agent

Abstract The biologic properties of a new oral antifertility agent, 2-phenyl-3-p-(β-pyrrolidinoethoxy)-phenyl (2:1,b) naphthofuran have been investigated in detail in rodent species and rhesus monkeys (Macaca mulatta). The compound causes 100% prevention of conception in rats, mice, and rhesus monkeys at a single oral dose of 10 mg/kg administered immediately postcoitum; the minimum effective dose (rats) in day 1–5 regime is 2 mg/kg. The antifertility effect is reversible. It shows mild estrogenic (uterotrophic) activity of short duration and slight antiestrogenicity; progestational, androgenic and antiandrogenic properties are absent, but the compound antagonizes progesterone action in ‘delayed implantation and ‘deciduoma induction tests. The pituitary, thyroid and andrenocortical function, and the menstrual cycle are not disturbed. The compound causes slight foetal resorption but no genital abnormalities or teratogenicity; the post-natal sexual development and subsequent fertility remain unimpaired. It prevents implantation through inhibition of deciduoma formation by virtue of its antiprogestational activity; tubal transport, fertilization, development and viability of ova are unaffected. The compound has a favorable therapeutic index.

Seasonal variations in daily sperm production rate of rhesus and bonnet monkeys

Daily sperm production (DSP) rate was estimated in adult male rhesus and bonnet monkeys to evaluate seasonal changes in the gametogenic activity of the testes. Three monkeys of each species were castrated during breeding and non‐breeding seasons and DSP rate was estimated by enumerating the homogenization‐resistant spermatid nuclei of steps 13 and 14. Results indicated a significant reduction in the DSP rate per testis during the non‐breeding season in two species, along with a marked decline in the testis weight. However, the gametogenic capacity of seminiferous tubules did not appear to be markedly affected during non‐breeding season, as the DSP rate per gram parenchyma of testis was only marginally reduced. The seasonal changes in DSP were much more pronounced in the rhesus than in the bonnet monkey. The feasibility of circanual rhythm in DSP of sub‐human primates to form a baseline for the study of reproductive function in male is discussed.

Flutamide as an Androgen Antagonist on Epididymal Function in the Rat

Die Wirkung von Flutamid als Androgenantagonist auf die Nebenhodenfunktion der Ratte