Alterations and reversibility of digestive and absorptive functions of rat intestine following medroxyprogesterone acetate administration

The long term (90 days) effects of medroxyprogesterone acetate (MPA) administration on the digestive and absorptive functions of the small gut have been investigated in female albino rats. The uptake of glucose and amino acids was found to be significantly increased while Ca++ uptake decreased following MPA treatment (35 mg/kg body weight). The observed increase in glucose uptake might be due to carrier mediated transport in enterocytes and not to a change in cell number. The Michaelis constant for glucose uptake was not altered by MPA. Activities of brush border membrane disaccharidases, leucine aminopeptidase and basolateral membrane enzyme Na+, K+-ATPase were significantly increased in response to MPA treatment. It was observed that these biochemical alterations caused by MPA in intestinal digestive and absorptive functions were reversible by 5 weeks after termination of the drug treatment. The action of the drug appears to closely resemble that of known effects of glucocorticoids on intestinal mucosa.     

Effects of 17 beta-estradiol and progesterone on intestinal digestive and absorptive functions in ovariectomized rats

The effects of low and high doses of 17 beta-estradiol and progesterone for 2 weeks on intestinal digestive and absorptive functions have been investigated in ovariectomized rats. The uptake of glucose was significantly enhanced following ovariectomy and administration of hormones restored the level of glucose uptake to that observed in sham-operated animals. Neither, the uptake of L-leucine nor calcium was affected after ovariectomy and treatment with the hormones. The activity of alkaline phosphatase (AP) of ileum was significantly elevated with the low and high doses of 17 beta-estradiol but in jejunum only at high doses. Progesterone alone did not alter AP activity but the combination of this hormone and 17 beta-estradiol significantly enhanced the jejunal and ileal AP activities. It seems that activity of AP is mainly under the control of 17 beta-estradiol. The activity of ileal disaccharidases and leucine aminopeptidase were enhanced at high doses of 17 beta-estradiol alone or in combination with progesterone whereas in the jejunum only AP activity was increased significantly. The present study indicates that 17 beta-estradiol plays an important role in regulating the activities of intestinal digestive enzymes and it is the ileal enzymes which are more prone to its action.     

Antifertility mechanisms of gossypol acetic acid in female rats

Gossypol acetic acid was administered orally (30, 60, 90 and 120 mg/kg/day) on Days 1-5 post coitum to mature female rats. At autopsy on Day 10, pregnancy in most treated animals (6/7 and 6/8) was blocked at high doses (90 and 120 mg/kg/day respectively). As the daily dose decreased to 60 mg/kg/day half (4/8) were not pregnant. However, at a lower dose (30 mg/kg/day), or at a single dose of 200 mg/kg at Day 1 p.c., pregnancy was not blocked. The concentrations of progesterone in the serum of these females were significantly decreased except at the low dose. The numbers of implantation sites in the treated females that did remain pregnant were similar to those in control females except at the dose of 120 mg/kg/day. Gossypol did not retard the development of the preimplantation embryo or cavitation. The Pontamine Blue test revealed that the drug did not interfere with the initiation of implantation. We suggest that gossypol has an antifertility effect in the female rat because it is luteolytic and disrupts post-implantation development.     

Studies on antifertility effects of gossypol acetic acid in domestic cocks

Daily oral administration of gossypol acetic acid (40 mg/kg body weight daily) resulted in a gradual decrease in the semen volume and sperm concentration. Fertility dropped to zero at the end of the treatment period. Activities of acrosin, hyaluronidase and angiotensin converting enzyme were also drastically decreased by the end of the treatment period. A loss of appetite, loss of body weight and morphological abnormalities in spermatozoa were noticed in the treated cocks. At 4 weeks after cessation of the treatment, full recovery of the above measures was recorded. Healthy chicks were hatched and were observed for several months.     

Inhibition kinetics of lactate dehydrogenase isoenzymes by gossypol acetic acid

The effect of gossypol acetic acid, a potent male sterilent was studied on LDH from goat liver (LDH-A4), heart (LDH-B4) and testis (LDH-C4) in vitro. All the preparations of LDH were inhibited by gossypol when the reaction was carried out in pyruvate-lactate (direct) or lactate to pyruvate (reverse) directions. The IC50 of gossypol for the pyruvate oxidation by LDH isozymes varied between 16 and 42 microM in presence of 0.27 mM pyruvate and 0.15 mM NADH at 25 degrees C and pH 7.4 whereas for the lactate oxidation, IC50 was 125 microM in a system containing 3.3 mM lactic acid and 1.8 mM NAD at 25 degrees C and pH 9.0. Reciprocal plots due to Lineweaver-Burk showed that these isozymes are inhibited in a non-competitive manner with respect to pyruvate and lactate, and in a competitive fashion when NAD and NADH were varied as substrates. Ki values of LDH-A4, -B4 and -C4 isozymes in presence of gossypol were 20, 34 and 29 microM against pyruvate; 33, 43 and 45 microM against NADH; 85, 85 and 125 microM against lactate and 94, 108 and 83 microM against NAD respectively.     

Effect of medroxyprogesterone acetate on the intestinal absorptive functions in protein-deficient rat

Effect of Medroxyprogesterone acetate (MPA) at a dose level of 35mg/Kg body weight per week for four weeks on the intestinal uptake of nutrients viz glucose, amino acids, (alanine and leucine), calcium and zinc has been investigated in protein-deficient female rats. The administration of MPA was found to enhance significantly the uptake of glucose and amino acids in both the pair-fed and the protein-deficient rats. In contrast, calcium uptake was depressed as a result of treatment with the drug as well as protein-deficiency. The uptake of zinc was not affected on drug administration. This steroidal contraceptive caused elevation in sodium-dependent glucose uptake, while the sodium-independent uptake remained unaltered. The kinetic parameters of glucose and leucine uptake indicate that MPA might be inducing the transport carrier protein of these nutrients as elevation in Vmax of these nutrients transport system was observed following its administration.     

Effects of semi-starvation on the total body composition and absorptive function of the small intestine of the young adult female rat.

Sixteen female rats aged about 80 days and with a mean body weight of 175 g were fed 40% of their ad libitum intake of a laboratory chow. They were killed and analysed for water, protein, lipid and ash after 9, 21-5, 30-2 and 38-8% of body weight had been lost. Compared to a control group of four animals, the 38-8% group lost 13 g or 34% of their protein. The animals in the 21-5, 30-2 and 38-8% groups lost 7-5 g or 87% of their lipid leaving only 1-1 g of lipid. The percentage protein in the body was little affected by body weight loss but lipid decreased from 5 to 1%. In another experiment with 26 rats of 205 g mean body weight and aged about 115 days, absorption rates by the small intestine were measured in vivo after variable weight losses between 0 and 39%. D(+)-Glucose uptake was increased by about 70% in those animals which had lost only 5% of body weight and this increased uptake was retained in those rats which had lost up to 39% of body weight. The absorption of L-leucine was not affected by the decline in body weight compared to the controls but relative to body weight, the ability of the intestine to absorb increased. In the same animals, the wet and dry weights of the small intestine declined slightly faster than body weight and the length of the small intestine tended to decrease slightly with increasing loss of body weight.     

醋酸胁迫对Acetobacter pasteurianus产酸呼吸链活力的影响

【目的】以巴氏醋酸杆菌工业菌株沪酿1.01和模式菌株Acetobacter pasteurianus ATCC33445为研究对象,研究工业菌株与模式菌株在高浓度醋酸胁迫下的产酸发酵时呼吸链酶活、相关基因转录水平的变化规律。【方法】检测两种菌株在0、1%、2%、3%不同初始醋酸浓度下的生物量、产酸以及酶活,并通过实时荧光定量PCR检测呼吸链相关酶合成基因的相对转录水平变化。【结果】两种菌株在1%初始醋酸浓度下产酸能力最强,发酵48 h平均产酸速度达到0.667 g/(L·h);两种菌株的ADH(乙醇脱氢酶)和ALDH(乙醛脱氢酶)酶活也达到最高,平均为12.01和9.77 U/mg;相关酶合成基因的相对转录水平较无底酸均提高。当初始醋酸浓度上升至2%和3%时,菌体酶活、产酸能力逐渐下降,呼吸链上的adh、cyt bd、cyt o和fap A基因转录水平上升,其余基因都降低。【结论】确定了巴氏醋酸杆菌在高初始浓度醋酸条件下,菌体会自发提高adh基因的转录水平,启动底物磷酸化,并将醋酸泵出到胞外;同时aldh基因的表达受到抑制,降低产酸,从而维持体内较低醋酸浓度。此外,呼吸链上其他外排相关酶转录水平也会提升,如cyt bd和cyt o,辅助底物磷酸化进程,加快释放能量。     

Effect of monensin on the Golgi apparatus of absorptive cells in the small intestine of the rat

Summary The effect of short-time treatment with the ionophore monensin, administered intraluminally at concentrations of 5 and 10 M, was studied on the Golgi apparatus of absorptive cells in the small intestine of the rat. At 2–3 min after treatment most of the Golgi stacks exhibited dilated cisternae. At 4–5 min stacked cisternae were absent; they were replaced by groups of smooth-surfaced vacuoles. Dilatation and vacuolization occurred in the entire stacks without preferential effect on any particular Golgi subcompartment.Monensin did not influence the cytochemical Golgi reaction of thiamine pyrophosphatase and acid phosphatase. The characteristic staining pattern of these two enzymes in all Golgi cisternae of absorptive cells in the proximal small intestine, and the reactivity restricted to trans cisternae in distal segments of the small intestine, were unchanged after treatment with monensin. In the distal small intestine, the cytochemical pattern allowed the monensin-induced vacuoles to be attributed to the former cisor trans-Golgi face. Further, the cytochemical results demonstrate that vacuolization is not restricted to the stacked cisternae, but includes the trans-most cisterna. The latter, usually located at some distance from the Golgi stacks, has been defined as belonging to the GERL system in several types of cells. The clear response to monensin, an agent that selectively affects the Golgi apparatus, indicates common properties between trans-most and stacked Golgi cisternae.     

Variable sister-chromatid exchange response in human lymphocytes exposed in vitro to gossypol acetic acid

Gossypol has potential for widespread use as a male oral antifertility agent in humans since it appears to be highly efficacious, with reversible spermatostatic effects and minimal side effects. Furthermore, it is both inexpensive and readily available. Therefore, a thorough understanding of gossypol's genotoxic potential is critical. Although genotoxicity studies have produced conflicting reports, increased sister-chromatid exchange (SCE) and DNA-strand breaks have been reported in human cells exposed to gossypol in vitro. In the present study, SCE was examined in purified human lymphocytes and whole blood cultures exposed to gossypol acetic acid at various concentrations in serum-free medium. A small but statistically significant increase in SCE was observed in pooled analysis of 7 donors in whole blood cultures exposed to 0.70 microM gossypol acetic acid (p less than 0.02). Individual analyses revealed only one donor with a significant SCE response (p less than 0.001). In subsequent experiments, exposure at higher doses had no effect on SCE frequencies. A small but significant increase in SCE was observed in ficoll/hypaque purified lymphocytes exposed to 0.07 and 0.70 microM gossypol acetic acid. Interpretation of SCE data with variable response is discussed.     

Effects of the male contraceptive agent gossypol on meiotic chromosomes of the male rat

Synaptonemal complexes (SCs) of rat spermatocytes were analyzed in silver-stained meiotic preparations 10-24 days after treatment with gossypol acetic acid, 30 mg/kg/day, for 70 days. Gossypol did not affect SC formation or function, as judged by the absence of pairing anomalies, SC fragmentation, or presynaptic arrest. The unpaired lateral axes could be seen at zygotene, and at pachytene normal SCs could be observed. The behavior of the XY axes also appeared to be normal.     

Effect of a steroidal oral contraceptive on intestinal absorptive functions in proteins deficient rat

The effects of steroidal oral contraceptive norethynodrel plus ethinylestradiol-3-methyl ether (SOC) at a daily dose of 5 mg: 0.06 mg per kg body weight for 28 days on intestinal absorptive functions have been investigated in protein-deficient female albino rats. The administration of this contraceptive caused significant increase in glucose and amino acids uptake but had no effect on calcium and zinc uptake in pair-fed as well as in protein-deficient rat. Further studies carried out on glucose transport system showed that the transport of sodium-dependent glucose was significantly enhanced while that of sodium-independent glucose remained unaltered in drug-treated animals. Kinetic studies of glucose transport in the presence of sodium ions revealed that SOC treatment affected the rate of uptake of glucose by elevating Vmax, but the apparent Kt value remained the same in treated and untreated animals.