Biomedical subjects

B S Setty

Publications and source records attributed to B S Setty.

At least 19 recordsLinked to original sources

PubMed2003

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.

Acrylates↗

PubMed2000

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.

Animals↗

PubMed1999

Changes in daily sperm production rate in rats under the influence of a potent antispermatogenic agent, CDRI 84/35.

CDRI 84/35, a potent nonsteroidal antispermatogenic agent, causes total sterility in rats by directly acting on germ cells while having no effect on Sertoli/Leydig cells. This study was conducted to evaluate the effect of the compound on gametogenic activity of testes and to identify stages of spermatogenesis that were affected. Adult male rats administered either compound 84/35 at minimum effective dose or estradiol (5 micrograms) or water only were killed on days 22, 41, and 64 of the treatment period to evaluate the effect on spermatid, spermatocyte, and spermatogonial stages, respectively. Daily sperm production (DSP) was measured employing a homogenization technique. Results showed a decline in testis weight and DSP with a drastic reduction (approximately 95%) in DSP in 84/35-treated rats on day 41 of the treatment period. Estradiol was more potent in reducing the testis weight; however, 84/35 had an edge over estradiol in reducing the DSP. After withdrawal of treatment for 120 days, a phenomenal recovery (> 90%) in DSP per gram parenchyma was noted in 84/35-treated animals. Results indicate a direct effect of estradiol on spermatogonia, whereas 84/35 seems to affect the spermatocyte stage.

Animals↗

PubMed1999

Endometrial steroid receptors during decidualization in rhesus monkey (Macaca mulatta); their modulation by anti-oestrogen CDRI-85/287.

With a view to elucidating the hormonal control of decidualization in rhesus monkey, we studied the effects of CDRI-85/287, a potent anti-oestrogen, on endometrial steroid receptors in vivo and in vitro. Compound 85/287 was administered (i.m.) on days 8, 9 and 10 of steroid treatment cycle at a dose of 15 mg/monkey. Deciduoma was induced on day 16. Histological examination of endometrial tissue on days 24 and 30 of the cycle showed an apparent inhibition in uterine epithelial and subepithelial decidual cell plaque formation and a decrease in leukocytic infiltration into the stroma in anti-oestrogen-treated animals. As observed on day 24, a significant decrease in progesterone receptors (PR) (nuclear + cytosolic) was observed in the 85/287-treated group, whereas oestrogen receptor (ER) content remained unaltered. On day 30 total ER as well as total PR content was markedly reduced in treated animals. In-vitro results clearly demonstrated a competitive antagonism of 85/287 at the ER level only. The results are discussed in relation to the histological changes and modulation of steroid receptors, thereby suggesting the decidualization inhibitory activity of anti-oestrogen molecule 85/287 in primate species.

Animals↗

PubMed1998

Estrogen, androgen and antiestrogen responses in the accessory organs of male rats during different phases of life.

Recent studies have indicated that estrogen has a stimulatory influence on the male reproductive tract. Evidence includes the presence of measurable levels of estrogen in the circulation, retention of exogenous estrogen, and presence of estrogen receptors in the male accessory sex organs during prepubertal life. In the present study, estrogen antagonists (CDRI-85/287 and centchroman) have been used to examine this concept by antagonising estrogen action at critical stages in the life in rat. Centchroman or 85/287 administration to 14 day old rats for 7 days did not alter gonadal or accessory organ weight. In contrast, in 21 day old castrated rats, treatment with either compound from day 28-35 of life stimulated an increase in all organ weights. When administered to normal rats during the critical phase of transition, i.e. days 30-60 of life, both testis and accessory organs showed an increase in weight. In contrast castrated rats treated with estrogen alone or in combination with 85/287 from days 37-45 of life and sacrificed on day 46 did not show any change, but 85/287 per se markedly reduced the weight of accessory organs. In adult castrated rats, the potency of DHT as a promoter of growth was potentiated by estradiol. Compound 85/287 negated the estradiol-induced increase. Glycerylphosphorylcholine (GPC) and sialic acid levels showed about 100% increase, with both high and low doses of 85/287 (treated from 30-60 days of life), However, centchroman (CDRI-67/20) was less potent in this regard. The effect of estrogen antagonists in relation to epididymal physiology during different phases of life in the rat is discussed.

Animals↗

PubMed1998

Effect of CDRI-85/287 on uterine estradiol and progesterone receptor levels/morphometric measurements during preimplantation period in rat.

Studies with 85/287, a potent nonsteroidal antiestrogen/antiimplantation agent were taken up. In this paper we report alterations in uterine morphometric measurements and estrogen/progesterone receptor levels under the influence of this compound. Results showed 32% decline in stromal absolute volume density on day 5 post-coitum (p.c.) only, whereas eosinophilic leucocyte number decreased both on days 3 and 5 p.c. (41%) in treated rat uterus. Epithelial mitotic activity showed complete cessation both in control and treated rats on day 5 p.c. Under the influence of the compound both cytosolic and nuclear estrogen receptor (ERc and ERn) levels decreased on day 3 p.c., but on day 5 p.c. ERn increased significantly. A significant increase was however noticed in progesterone nuclear receptors (PRn) on day 5 p.c. On the whole our studies showed overall significant changes in uterine morphometric measurement/estrogen and progesterone receptor levels during the preimplantation period in rat under the influence of compound 85/287, causing asynchrony of events and thus failure of implantation.

Animals↗

PubMed1998

Lipid metabolising enzymes in isolated rat testicular germ cells and changes associated with meiosis.

To assess the lipid metabolising potential of testicular germ cells undergoing meiosis, spermatocytes and spermatids were isolated from adult rat testis and purified by centrifugal elutriation followed by density gradient centrifugation. Seven key enzymes of lipid metabolism (namely beta-hydroxybutyrate dehydrogenase, carnitine acetyl transferase, ATP citrate lyase, hydroxyacyl-CoA dehydrogenase, glycerol 3-phosphate dehydrogenase, acetyl-CoA carboxylase and long chain acyl-CoA synthetase) were assayed in cell homogenates. The results indicated that germ cells possess the key enzymes for de novo synthesis and oxidation of fatty acids. The significant increase in activities of anabolic enzymes and decrease in activities of catabolic enzymes in post-meiotic germ cells indicated a shift in lipid metabolism towards fatty acid synthesis during meiosis. Long chain acyl-CoA synthetase activity was not detected in the two cell types. The study indicates a major reorganization of fatty acid turnover during meiosis with equilibrium shifting in favour of synthesis.

3-Hydroxyacyl CoA Dehydrogenases↗

PubMed1998

Changes in carbohydrate metabolism of testicular germ cells during meiosis in the rat.

A study was undertaken to estimate the activities of the key enzymes of glycolysis, the pentose phosphate pathway and the tricarboxylic acid (TCA) cycle in purified rat spermatocytes and spermatids, which have been shown to die in glucose-containing medium and require lactate/pyruvate for maintaining normal ATP concentrations. The aim was to elucidate the changes in the glycolytic and oxidative potential of germ cells undergoing meiosis. Pachytene spermatocytes and round spermatids from adult rat testis were purified to approximately 90% purity by trypsin digestion followed by a combination of centrifugal elutriation and Percoll density gradient centrifugation. After the purity and viability of these cells had been established, their contents of hexokinase, phosphofructokinase, lactate dehydrogenase (LDH) and LDH-X of glycolysis, glucose 6-phosphate dehydrogenase of the pentose phosphate pathway and citrate synthase, aconitase, malate dehydrogenase and 2-oxoglutarate dehydrogenase of the TCA cycle were estimated. These enzymes were also estimated in epididymal spermatozoa for comparison with the testicular germ cells. The results indicate greater activity of glycolytic and pentose phosphate pathway enzymes in spermatocytes than in spermatids, which exhibited greater activity of TCA cycle enzymes than the former. The difference in activity was statistically significant for most of the enzymes studied. In contrast, spermatozoa exhibited markedly greater activity of glycolytic enzymes and significantly lower activity of pentose phosphate pathway and TCA cycle enzymes than did the testicular germ cells. We conclude that the unusual dependence of spermatids exclusively on lactate may be due to their lower glycolytic potential, whereas spermatocytes with comparatively greater glycolytic activity have an intermediate dependence on lactate and are therefore able to utilise lactate, pyruvate, or both, while retaining a better ability to utilise glucose. Spermatozoa with the greatest glycolytic potential and the lowest TCA cycle activity appear to be 'programmed' to utilise exclusively glucose/fructose for energy.

Animals↗

PubMed1998

Effect of CDRI-85/287, a potent antiimplantation agent on uterine endometrial dimensions and peroxidase levels in rat.

CDRI compound 85/287 a potent estrogen antagonist and antiimplantation agent in rat was studied to elucidate its mechanism of action. In ovariectomized rats 85/287 treatment antagonized estrogen stimulated uterine volume density, eosinophil leucocyte infiltration, stromal mitotic cell number and peroxidase activity. In parallel experiments in pregnant rats, uterine peroxidase activity also decreased significantly as compared to controls on day 5 post-coitum. The results show that 85/287 exerts its antiimplantation activity by inhibition of responses to estradiol action.

Animals↗

PubMed1997

Effect of antispermatogenic compound CDRI-84/35 on marker enzymes of rat testis cells. A study on site of action.

Marker enzymes of Sertoli and germ cells were estimated to study the mechanism of action of antispermatogenic compound CDRI 84/35 in adult male rat testis. Animals were killed after 22, 41, and 64 days of treatment with antispermatogenic dose of CDRI 84/35 in order to evaluate the effect of the compound on spermatid, spermatocyte, and spermatogonial stages, respectively. Studies were also extended to a recovery period of 90 days. Results indicate a direction action of the compound on germ cells, with no apparent effect on Sertoli cells. Studies also show a massive depletion of postmeiotic germ cells after the treatment, with some damage to premeiotic germ cells as well. Reversibility of the compound was partial, with the marker enzymes of pre- and postmeiotic germ cells not being restored to control levels after withdrawal of treatment.

Animals↗

PubMed1997

Response of the postnatal rat epididymis to estrogen & antiestrogens.

The effect of androgen and estrogen antagonists on estrogen induced responses in the epididymis of rat was studied. Estradiol benzoate administered to male rates on day 5 of life increased the epididymal weight, absolute volume density of fibromuscular stroma and its eosinophilic leucocyte numbers. Testosterone administration (day 5 life) alone did not have any stimulatory effect on the epididymis as an organ or its peroxidase activity on days 15 or 20 of life. On the other hand, testosterone/85/287 negated estradiol induced increase in the absolute volume density, eosinophilic leucocyte accumulation and peroxidase activity. Tamoxifen (Tam) with inherent estrogenic activity acted both as an agonist and an antagonist. Results of present studies support the contention that nonsteroidal antiestrogens (CDRI-85/287 and Tam) can modulate estradiol induced epididymal responses during the postnatal period of male rat.

Animals↗

PubMed1997

Seasonal variations in Sertoli and germ cell marker enzymes in testis of rhesus and bonnet monkeys.

Variations in specific activities of the marker enzymes of Sertoli and germ cells during breeding (November-December) and non-breeding (May-June) seasons were investigated in rhesus and bonnet monkeys maintained under laboratory conditions. The marker enzymes selected for testicular cells were-Sertoli cells: beta-glucuronidase, gamma-glutamyl transpeptidase; pre-meiotic germ cells: glucose 6-phosphate dehydrogenase, malate dehydrogenase, alpha-glycerophosphate dehydrogenase; mature germ cells: LDH-X, sorbitol dehydrogenase. Results have indicated significant seasonal variation in marker enzymes only in rhesus testis. Marker enzymes of Sertoli cell increased while those of germ cell decreased significantly during non-breeding season. Marker enzymes of mature germ cells were affected much more drastically than those of the pre-meiotic germ cells.

Animals↗

PubMed1995

Activities and androgenic regulation of lysosomal enzymes in the epididymis of rhesus monkey.

The activities and androgenic regulation of seven lysosomal enzymes viz. acid phosphatase, N-acetyl hexosaminidase, alpha-mannosidase, beta-glucuronidase, DNase II, RNase II and phospholipase A was established in caput, corpus and cauda segments of monkey epididymis. Estimation of enzyme activities in the the epididymis of control, castrated and castrated-androgen replaced monkeys revealed that all the enzymes except RNase II showed higher activity in caput and corpus as compared to cauda. The enzymes were reduced markedly after castration and on subsequent androgen replacement there was a significant stimulation of the repressed activities, but the control levels were not restored. RNase II showed highest activity in cauda which was further elevated after castration. The possible role of these enzymes in sperm maturation and disposal is discussed.

Androgens↗

PubMed1994

Structure activity relationship of some 2,3-diaryl-2H-1-benzopyrans to their anti-implantation, estrogenic and antiestrogenic activities in rat.

In an endeavour to develop potent anti-implantation agents, a new antiestrogen, CDRI 85/287 (2-(4-2-piperidinoethoxy)phenyl-3-phenyl(2H)benzo(b)pyran), virtually devoid of agonistic activity, was identified. The present study deals with anti-implantation and estrogen agonistic-antagonistic activities of four structural analogues of 85/287. Results show that none of the compounds induced vaginal cornification, even at doses as high as 2.5 mg/kg. Compounds having p-hydroxyphenyl group at position-3 or hydroxy group at position-7 showed better estrogen receptor affinity (6.6 and 25.3% E2) as well as antiestogenic activity. When 3-p-hydroxyphenyl was replaced by 3-p-methoxyphenyl, a marked reduction in the receptor affinity was observed. However, this compound was relatively more potent as an anti-implantation agent, possibly due to its conversion to hydroxylated metabolite in vivo. The provision of aminoethoxy side chain at para-position and a shift in the piperidinoethoxy side chain from position-4 to position-2 in these molecules resulted in a decrease in estrogenicity and increase in antagonistic property. Results are discussed with regard to molecular configuration, relative binding affinity of these compounds to their biological profile.

Animals↗

PubMed1994

Activities and androgenic regulation of kreb cycle enzymes in the epididymis and vas deferens of rhesus monkey.

The activities of nine enzymes of the TCA cycle were estimated in the initial segment, caput, corpus and cauda segments of epididymis and vas deferens of adult rhesus monkey and expressed as units per mg DNA. These enzymes were also estimated in epididymal segments and vas deferens of castrated and castrated-androgen replaced monkeys as well. Results indicated higher activities of most of the enzymes in vas deferens as compared to epididymal segments. All the enzymes showed marked reduction in epididymis and vas deferens after castration, the effect being much more pronounced in the epididymis, than in the vas. Androgen replacement in castrated monkeys stimulated most of the enzymes markedly in epididymis and in the vas deferens as compared to their castrated values. The response of cauda and vas deferens to exogenous androgen treatment was however moderate, as compared to the other epididymal segments. The studies indicate that energy metabolism in the epididymis (as well as in the vas deferens) is strictly androgen dependent and the energy charge of these target organs is likely to fall appreciably after castration, which may in turn affect many energy dependent processes of these organs (e.g. absorption, secretion of specific substances etc.) which have been considered important for sperm maturation and survival.

Androgens↗

PubMed1993

Effect of a pure nonsteroidal antiestrogen, CDRI-85/287, on implantation--associated histological and biochemical changes in the rat uterus.

The effect of compound CDRI-85/287, a pure, nonsteroidal antiestrogen, on implantation-associated changes in rat uterus were studied. Results provide a clear correlation between the antideciduogenic action of 85/287 (0.05 mg/kg in days 1-5 post-coitum or 2.5 mg/kg on day 1 post-coitum) and the time of its administration in relation to the secretion of prenidatory luteal phase estrogen. The antiestrogenic nature of the compound is further highlighted by inhibition of estradiol-induced increase in vascular permeability. In the present study, differences in the pattern of biochemical maturation of the pregnant, pseudopregnant and 85/287-treated rat uterus have also been illustrated. As compared to the pregnant rat uterus, absence of (the blastocyst and) decidualizing tissue in the pseudopregnant rat uterus accounts for the low uterine weight, protein, RNA, phospholipids and alkaline phosphatase at the time of implantation. Post-coital treatment with 85/287 (2.5 mg/kg, oral) inhibited increase in these parameters at the time of implantation. Glycogen levels which were lowered in the pregnant rat uterus on days 5 and 6, remain unaltered in the pseudopregnant and 85/287-treated rat uteri, suggesting nonutilization of this energy substrate. These findings provide sufficient evidence that the antiimplantation activity of 85/287 is due to its antiestrogenic property.

Alkaline Phosphatase↗

PubMed1993

Androgenic regulation of glycolytic and HMP pathway in epididymis and vas deferens of rhesus monkey.

The androgenic regulation of the eleven enzymes of glycolytic pathway and two key enzymes of HMP pathway was studied in the initial segment, caput, corpus and cauda regions of the epididymis and in the vas deferens of rhesus monkey. The specific activities of enzymes were expressed as units of activity per mg DNA. Results in control animals indicate a marked difference in energy metabolism of epididymis and vas deferens. However, the epididymal duct itself did not show much regional variation in enzyme activities along its length. All the enzymes of the two pathways studied showed significant reduction after castration, the regulatory enzymes being affected more severely. On treatment with exogenous dihydrotestosterone, most of these enzymes showed stimulation in castrated monkeys, but none of them could be restored to normal level. The stimulation of these enzymes on treatment with exogenous dihydrotestosterone varied along the epididymal duct itself being maximum in the initial segment and minimum in the cauda region. The changes in the vas deferens were less marked as compared to the epididymis following castration and androgen replacement.

Animals↗

PubMed1992

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.

Animals↗