Hr In Male Rats Research Articles

Estrogen Accelerates Cell Proliferation through Estrogen Receptor α during Rat Liver Regeneration after Partial Hepatectomy.

Although estrogen is implicated in the regulation of cell growth and differentiation in many organs, the exact mechanism for liver regeneration is not completely understood. We investigated the effect of estrogen on liver regeneration in male and female Wistar rats after 70% partial hepatectomy (PHx) and performed immunohistochemistry, western blotting and Southwestern histochemistry. 17β-estradiol (E2) and ICI 182,780 were injected into male rats on the day before PHx. The proliferating cell nuclear antigen (PCNA) labeling index reached a maximum at 48 hr after PHx in males, and at 36 hr in females and E2-treated male rats. Estrogen receptor α (ERα) was expressed in zones 1 and 2 in male rats, but was found in all zones in female rats. Interestingly, ERα was not detected at 6–12 hr after PHx but was found at 24–168 hr in male rats. However, ERα expression was found at all sampling time-points in female and E2-treated male rats. The activity of estrogen responsive element binding proteins was detected from 12 hr after PHx in male rats but was found from 6 hr in female and E2-treated male rats. ERα was co-expressed with PCNA during liver regeneration. These results indicate that estrogen may play an important role in liver regeneration through ERα.

Bile secretory characteristics of β-muricholate and its taurine conjugate are similar to those of ursodeoxycholate in the rat

Ursodeoxycholate (UDC) has very high biliary transport maxima values (Tm) for its conjugates as well as the capability of inducing choleresis rich in bicarbonate concentration in the bile in rats. We examined in the present study whether these properties are shared by β-muricholate (β-MC), using β-MC, α-muricholate (α-MC) and tauro-β-MC (Tβ-MC) in the rat. Bile samples were collected every 20 min for 2 hr in male rats under the infusion of α- or β-MC (1.2 μmol/min/100g). The choleretic response was quicker in β-MC infused rats than in rats infused with α-MC. Bile salt excretion rates increased radically in both experiments. However, in β-MC infused rats, the bile salt excretion rate began to decrease after 40 min, whereas in α-MC infused rats, it continued to increase after 1 hr. Bile bicarbonate concentration significantly increased in β-MC infused rats but not in α-MC infused rats. The Tm of Tβ-MC was 2 times higher than the Tm value for taurocholate and was comparable to that of tauroursodeoxycholate (TUDC) which was previously found by the authors. The bile flow (Y, μl/min/100 g) was significantly correlated with the bile salt excretion rate (X, μmol/min/100 g) [Y=(6.90±0.24)X+ (5.55 ± 1.06), n=41, −0.98, P<0.01)], the slope value being higher than that found for TUDC. The results suggest that UDC and β-MC (and their conjugates) have very similar bile secretory characteristics and may probably share the same transport system in the rat.

Studies on the Metabolic Fate of Betamethasone Butyrate Propionate. (IV). Absorption, distribution and excretion in rats and rabbits.

3H-BBPをラットおよびウサギに0.25mg/kgで経皮(非密封法)，あるいは1mg/kgで皮下投与し，その吸収，分布，排泄について検討し，以下の結果を得た．1．軟膏またはクリームを正常皮膚動物に経皮投与した際，全身系への経皮吸収率は雄性ラットでは約3～5%，雌性ラットでは約14%，また雄性ウサギでは約14%であった．損傷皮膚雄性ラットでは約30～50%であった．2．正常皮膚動物における血液または血漿中放射能濃度の最高到達時間および最高値は雄性ラット:24時間，0.6～0.8ng/ml，雌性ラット:8時間，4.7ng/ml雄性ウサギ:13時間，3.0ng/mlであった．また，損傷皮膚雄性ラットでは5時間，8.6～15.7ng/mlであった．3．主排泄経路はラットでは糞であったが，ウサギの尿糞中排泄率の割合はほぼ同じであった．4．正常皮膚雄性ラットにおける組織内放射能濃度は，投与後8時間あるいは24時間に最高濃度を示し，肝臓，腎臓副腎，貯精嚢および膀胱に高い濃度が認められた．各組織からの消失は緩慢であり，特に血液かbの消失が遅延した．塗布部皮膚のミクロオートラジオグラムより，BBPの経皮吸収経路として付属器官を経由するルートと経表皮ルートが確認された．5．正常皮膚雄性ラットに7回反復投与した際，毎回投与後24時間における血液および組織中放射能濃度は，投与回数に伴い上昇する傾向を示した．7回投与後の血液および組織中からの放射能の消失は緩慢であったが，7回投与後の尿および糞中排泄率は単回投与群と相違が認められなかった．6．妊娠ラットに3H-BBPを皮下投与した際の全身オートラジオグラムより，胎盤通過性が確認されたものの，放射能が胎仔組織に残留する傾向は認められなかった．

Renal glutathione depletion and nephrotoxicity of cadmium-metallothionein in rats

Renal glutathione (GSH) concentrations were reduced approximately 80% at 4 hr after a single injection of buthionine sulfoxime (BSO) (4 mmol/kg body wt) and remained reduced for at least 16 hr in male rats. Following BSO injection, rats were injected with a nephrotoxic dose of cadmium-metallothionein (Cd-MT) (0.3 mg Cd as Cd-MT/kg body wt) and killed 1, 4, or 12 hr later. Damage to the kidney was assessed histologically and by measurement of p-aminohippuric acid (PAH) uptake into renal cortical slices. Although the renal accumulation of Cd following Cd-MT injection was significantly lower in BSO-pretreated rats as compared to nonpretreated rats, the damage to kidney was more severe. At 4 and 12 hr, both Cd-MT-induced inhibition of PAH uptake and morphological damage were significantly increased in BSO-pretreated rats. In certain experiments, the induction of renal intracellular MT synthesis by zinc pretreatment slightly decreased the renal toxicity of Cd-MT in the BSO-treated rats. The results demonstrate that although GSH depletion decreases the renal accumulation of Cd in rats injected with Cd-MT, the nephrotoxicity of Cd-MT is increased. Preinduction of MT in the kidney can only partially overcome this increase in toxicity. Therefore both GSH and intracellular MT levels can influence the renal toxicity of injected Cd-MT.

STUDIES ON THE FUNCTION OF CELL MEMBRANE 2ndREPORT: ELEVATION OF NADH-CYTOCHROME c REDUCTASE ACTIVITE IN THE LIVER CELL MEMBRANE OF RATS FOLLOWING CCl4 ADMINISTRATION

AbstractDistinct fractional zones of cell membranes in sucrose gradients were obtainable from homogenates of rat liver up to 6 hr (females) and 12 hr (males) following an i.p. injection of CCl4 (0.2 ml/kg body wt.). CCl4 administration to rats caused a marked elevation of NADH-cytochrome c reductase activity in the liver cell membrane. There was a remarkable difference between sexes with respect to time-course of the changes of the enzyme activity, viz., a peak was reached 6 hr after administration in female rats and 12 hr in male rats with normal activity at 6 hr. Neither mitochondrial fractions nor microsomal fractions of rat liver displayed any significant alterations in NADH-cytochrome c reductase activity 6 hr after CCl4 administration.

Sex difference in hypertensive action of metopirone in relation to its plasma levels in the rat.

200 mg/kg of Metopirone (2- methyl-1, 2-bis-(3-pyridyl)-l-propanone; Su-4885) was administered to intact male and female rats perorally once daily for 30 days with 1% sodium chloride solution to drink. Systolic blood pressure of female rats was elevated to a greater degree and more constantly than that of male rats. Metopirone caused in female rats a fall in adrenal vein corticosterone which was greater than that which occurred in male rats. In addition, Metopirone caused a secretion of deoxycorticosterone which lasted 16 hr in female rats but no longer than 8 hr in male rats. Metopirone was found in peripheral plasma obtained at 16 hr after peroral administration in female rats but not in male rats. Biological half-time of Metopirone was 120 min for female rats and 49 min for male rats. There were found at least 3 metabolites of Metopirone in peripheral blood. Combined levels of the metabolites at 30 min after peroral administration were higher in male rats than in female rats. From these findings it was...

細胞膜機能に関する研究

NADH-cytochrome c reductase activity of liver cell membrane fraction was remarkably elevated after CCl4 administration and reached a peak in 6hr in female and 12hr in male rats, when separation of cell membrane was not disturbed. In female rats, microsomal and mitochondrial enzyme activities were not significantly influenced 6hr after CCl4 administration. The isolation procedure was adequate in separating membrane from microsome or mitochondria 6hr after CCl4 administration in female rats. Elevation of this enzyme activity in cell membrane is considered to be due to specific changes in cell membrane rather than to contamination of mitochondrial or microsomal particles in the course of separation.