Effects of relaxin on systemic arterial hemodynamics and mechanical properties in conscious rats: sex dependency and dose response

2005 ◽  
Vol 98 (3) ◽  
pp. 1013-1020 ◽  
Author(s):  
Dan O. Debrah ◽  
Kirk P. Conrad ◽  
Lee A. Danielson ◽  
Sanjeev G. Shroff
Keyword(s):  
Dose Response ◽  
Arterial Compliance ◽  
Chronic Administration ◽  
Late Pregnancy ◽  
High Serum ◽  
Late Gestation ◽  
Female Rats ◽  
Male Rats ◽  
Serum Concentrations ◽  
Arterial Load

We previously showed that chronic administration of recombinant human relaxin (rhRLX; 4 μg/h) to conscious female, nonpregnant rats to reach serum levels corresponding to early to midgestation (∼20 ng/ml) increases cardiac output (CO) and global arterial compliance (AC) and decreases systemic vascular resistance (SVR), comparable to changes observed in midterm pregnancy. The goals of this study were to test whether chronic administration of rhRLX (4 μg/h) to conscious male rats will yield similar changes in CO and systemic arterial load and to determine whether higher infusion rates of rhRLX (50 μg/h) administered to nonpregnant female rats yielding serum concentrations corresponding to late pregnancy (∼80 ng/ml) will further modify CO and SVR and global AC comparable to late gestation. CO and systemic arterial load, as quantified by SVR and AC, were obtained by using the same methods as in our previous studies. With respect to baseline, chronic rhRLX administration to male rats over 10 days at 4 μg/h increased both CO (20.5 ± 4.2%) and AC (19.4 ± 6.9%) and reduced SVR (12.7 ± 3.9%). These results were comparable to those elicited by the hormone in nonpregnant female rats. In contrast, neither acute (over 4 h) nor chronic (over 6 days) infusion of the higher dose of rhRLX administered to conscious female rats resulted in significant changes in CO, AC, or SVR from baseline. We conclude that 1) rhRLX increases CO and AC and reduces SVR irrespective of sex, and 2) the rhRLX dose response is biphasic insofar as significant alterations in CO and systemic arterial load fail to occur at high serum concentrations.

Impact of gender and endothelin on renal vasodilation and hyperfiltration induced by relaxin in conscious rats

2000 ◽  
Vol 279 (4) ◽  
pp. R1298-R1304 ◽  
Author(s):  
Lee A. Danielson ◽  
Laurie J. Kercher ◽  
Kirk P. Conrad
Keyword(s):  
Renal Plasma Flow ◽  
Plasma Osmolality ◽  
Chronic Administration ◽  
Sodium Concentration ◽  
Female Rats ◽  
Male Rats ◽  
Receptor Subtype ◽  
Serum Concentrations ◽  
Renal Circulation ◽  
Pregnant Rats

Chronic administration of the hormone relaxin elicits renal vasodilation that is dependent on nitric oxide (NO) in both conscious intact and ovariectomized female rats. Our first objective was to test whether the hormone, when administered to approximate serum concentrations found in midterm pregnant rats, induces renal vasodilation in males. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) increased significantly, on average, by 33 and 49% over baseline, respectively, after 5 days of recombinant human relaxin (rhRLX) administration to 12 conscious male rats by subcutaneous osmotic minipump. There were also significant decreases in hematocrit, plasma osmolality, and sodium concentration. Another objective was to determine whether endogenous endothelin (ET; via the endothelial ETB receptor) mediates the NO-dependent renal vasodilation produced by relaxin. rhRLX or vehicle was administered to conscious female rats ( n = 9 and 8 rats, respectively). On the fifth day, baseline GFR and ERPF were both increased, on average, by 20–30% in the rats administered rhRLX ( P < 0.05 vs. vehicle). Next, the specific ETB-receptor antagonist RES-701-1 was infused intravenously over 4 h in both groups of rats. In response to RES-701-1, there was a significant decline in both GFR and ERPF in the rats receiving rhRLX such that renal function converged in the two groups of animals. We conclude 1) relaxin induces marked changes in the renal circulation and in osmoregulation regardless of gender and 2) relaxin-induced renal vasodilation and hyperfiltration are mediated by endothelin through the endothelial ETB receptor subtype and NO.

Regulation of renal CYP4A expression and 20-HETE synthesis by nitric oxide in pregnant rats

2003 ◽  
Vol 285 (2) ◽  
pp. F295-F302 ◽  
Author(s):  
Mong-Heng Wang ◽  
Jishi Wang ◽  
Hsin-Hsin Chang ◽  
Barbara A. Zand ◽  
Miao Jiang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Rat Kidney ◽  
Late Pregnancy ◽  
Inhibitory Effect ◽  
Female Rats ◽  
Male Rats ◽  
Pregnant Rats ◽  
Renal Vasoconstriction ◽  
Dependent Inhibition

20-Hydroxyeicosatetraenoic acid (20-HETE), which promotes renal vasoconstriction, is formed in the rat kidney primarily by cytochrome P-450 (CYP) 4A isoforms (4A1, 4A2, 4A3, 4A8). Nitric oxide (NO) has been shown to bind to the heme moiety of the CYP4A2 protein and to inhibit 20-HETE synthesis in renal arterioles of male rats. However, it is not known whether NO interacts with and affects the activity of CYP4A1 and CYP4A3, the major renal CYP4A isoforms in female rats. Incubation of recombinant CYP4A1 and 4A3 proteins with sodium nitroprusside (SNP) shifted the absorbance at 440 nm, indicating the formation of a ferric-nitrosyl-CYP4A complex. The absorbance for CYP4A3 was about twofold higher than that of CYP4A1. Incubation of SNP or peroxynitrite (PN; 0.01–1 mM) with CYP4A recombinant membranes caused a concentration-dependent inhibition of 20-HETE synthesis, with both chemicals having a greater inhibitory effect on CYP4A3-catalyzed activity. Moreover, incubation of CYP4A1 and 4A3 proteins with PN (1 mM) resulted in nitration of tyrosine residues in both proteins. In addition, PN and SNP inhibited 20-HETE synthesis in renal microvessels from female rats by 65 and 59%, respectively. We previously showed that microvessel CYP4A1/CYP4A3 expression and 20-HETE synthesis are decreased in late pregnancy. Therefore, we investigated whether such a decrease is dependent on NO, the synthesis of which has been shown to increase in late pregnancy. Administration of NG-nitro-l-arginine methyl ester (l-NAME) to pregnant rats for 6 days ( days 15- 20 of pregnancy) caused a significant increase in systolic blood pressure, which was prevented by concurrent treatment with the CYP4A inhibitor 1-aminobenzotriazole (ABT). Urinary NO2/NO3 excretion decreased by 40 and 52% in l-NAME- and l-NAME + ABT-treated groups, respectively. Interestingly, renal microvessel 20-HETE synthesis showed a marked increase following l-NAME treatment, and this increase was diminished with coadministration of ABT. These results demonstrate that NO interacts with CYP4A proteins in a distinct manner and it interferes with renal microvessel 20-HETE synthesis, which may play an important role in the regulation of blood pressure and renal function during pregnancy.

Subchronic Toxicity of Thalidomide in Rodents After 13 Weeks of Oral Administration

1999 ◽  
Vol 18 (5) ◽  
pp. 337-352 ◽  
Author(s):  
Steve K. Teo ◽  
Nancy J. Trigg ◽  
Mary E. Shaw ◽  
J. Michael Morgan ◽  
Steve D. Thomas
Keyword(s):  
Food Consumption ◽  
Dose Response ◽  
Clinical Chemistry ◽  
Female Rats ◽  
Male Rats ◽  
Lumbar Spinal Cord ◽  
High Dose ◽  
Significant Finding ◽  
Lower Body ◽  
Body Weights

The subchronic toxicology of thalidomide was determined in CD-1 mice and F344 rats. Animals (10/sex/dose) were orally dosed at 30,300, and 3000 mg/kg/day over 13 weeks. Control animals were given 1% carboxymethylcellulose. No thalidomide-related mortality occurred throughout the study. Some species and sex differences were seen. In mice, thalidomide had no effect on body weight, food consumption, ophthalmic function or clinical chemistry/hematology, but a dose-dependent orange-pink urine was observed in both sexes. The discoloration was probably due to chromogenic breakdown products of thalidomide. The only significant finding in the mouse study was dose-related hepatic centrilobular hypertrophy in the males. This appeared only at the highest dose in the females. The hypertrophy was correlated with increased liver weight for the high dose of both sexes suggesting enzyme induction. In rats, thalidomide produced lower body weights in both sexes compared to control with a dose-response more evident in males. Male rats dosed at 30, 300, and 3000 mg/kg had body weights that were 8, 11, and 19% below control weight just before necropsy. Corresponding female rats were only 6–7% below control weights at all dose levels. Lower food consumption was observed in male rats and varied between 6–13% below control with no dose-response. Decreased forelimb strength was noted in males and could be due to the lower body weights. Functional observational battery tests and histopathology of the sural nerve and lumbar spinal cord sections suggested that the rat did not develop thalidomide-induced peripheral neuropathy. Mild anemia and leukopenia were seen only in some treated males. A decrease in total and free T4 was more consistent in females. Both sexes had lower thymus weights with no histological correlate compared to control. The no-observed-adverse-effect level for mice and female rats were 3000 mg/kg and 30 mg/kg for male rats.

N-(3,5-dinitrophenyl)-5-methoxytryptamine, a novel melatonin antagonist: effects on sexual maturation of the male and female rat and on oestrous cycles of the female rat

1988 ◽  
Vol 116 (1) ◽  
pp. 43-53 ◽  
Author(s):  
M. Laudon ◽  
Z. Yaron ◽  
N. Zisapel
Keyword(s):  
Drinking Water ◽  
Adult Female ◽  
Sexual Maturation ◽  
Young Male ◽  
Female Rats ◽  
Male Rats ◽  
Female Rat ◽  
Simultaneous Administration ◽  
Serum Concentrations ◽  
The Brain

ABSTRACT N-(3,5-dinitrophenyl)-5-methoxytryptamine (ML-23) has recently been synthesized and shown to antagonize the inhibitory effect of melatonin on the release of dopamine in vitro from the hypothalamus of female rats. In the present study the ability of ML-23 to inhibit in vivo the following melatonin-mediated effects was investigated: (1) delayed sexual maturation of young male rats, (2) delayed sexual maturation of young female rats, (3) inhibition of ovulation in mature female rats and (4) re-establishment of oestrous cycles in adult female rats maintained in continuous light. The inhibitory effect of daily melatonin injections, given in the afternoon, on the growth of the prostate gland and seminal vesicles and on serum testosterone concentrations in young male rats was prevented by daily injections of ML-23. Daily injections of ML-23 alone did not affect sexual maturation of young rats. In young male rats treated through the drinking water with melatonin, the growth of the accessory sex organs, but not that of the testes, was delayed and serum concentrations of testosterone were lower than in untreated rats. Administration of ML-23 through the drinking water increased serum concentrations of testosterone but did not significantly affect the weights of the accessory sex organs. Simultaneous administration of ML-23 and melatonin through the drinking water prevented completely, in a dose-dependent manner, the melatonin-mediated decrease in epididymal weights and in serum concentrations of testosterone and partially inhibited the delayed growth of the prostate glands and seminal vesicles. In young female rats treated with melatonin through the drinking water for 30 days, the growth of the ovaries was inhibited and serum concentrations of oestradiol were lower than in untreated rats. The growth of the uterus was not significantly affected. Administration of ML-23 through the drinking water did not significantly affect uterine and ovarian weights or oestradiol concentrations. Simultaneous administration of melatonin and ML-23 through the drinking water prevented completely the melatonin-mediated decrease in ovarian weights and in serum oestradiol concentrations. Ovulation during presumptive oestrus was prevented in adult female rats treated through the drinking water for 7 days with melatonin. Administration of ML-23 alone did not significantly affect the average numbers of ova shed and corpora lutea present. Simultaneous administration of ML-23 and melatonin prevented completely the melatonin-mediated inhibition of ovulation; the average number of ova shed was the same as in controls. Suppression of reproductive cycles occurred in adult female rats after long-term exposure to continuous light. This suppression was prevented by daily injections of melatonin in the afternoon; the incidence of constant oestrus decreased by 80%. Simultaneous injection of ML-23 and melatonin into rats maintained under continuous illumination prevented the effect of melatonin, and all the animals remained in constant oestrus. Administration of ML-23 alone did not alter the incidence of constant oestrus. A tritium-labelled derivative of ML-23 was prepared and administered orally to male rats. Peak concentrations of ML-23 occurred in the blood within 30 min after feeding and disappeared subsequently with a half-life of about 42 min. Intraperitoneal injection of [3H]ML-23 resulted in the appearance of peak concentrations of the drug in the brain within 20 min. The effects of ML-23 on serotonin S1 and S2 receptors, dopamine D2 receptors and melatonin receptors in the brain of the male rat were investigated using [3H]serotonin, [3H]spiperone and 2-[125I]iodomelatonin respectively. The binding of [3H]serotonin to brain synaptosomes and of [3H]spiperone to synaptosomes prepared from the cortical and caudate regions of the cerebrum was unaffected by ML-23 (10 μmol/l), whereas the binding of 2-[125I]iodomelatonin to brain synaptosomes was entirely inhibited. The results demonstrate the potency of ML-23 in antagonizing melatonin-mediated effects in the male and female rat in vivo. The drug may be administered to the animals simply through the drinking water, for relatively long periods without apparent deleterious effects on survival and welfare. ML-23 is accessible to both central and peripheral sites and acts specifically on melatonin but not on serotonin or dopamine receptors in the brain. The availability of a melatonin antagonist offers new opportunities for exploring the physiological role of melatonin in the neuroendocrine system. J. Endocr. (1988) 116, 43–53

A FEMALE-LIKE RISE IN LUTEINIZING HORMONE AND FOLLICLE-STIMULATING HORMONE AFTER GONADECTOMY IN MALE RATS INDUCED BY OESTRADIOL PRETREATMENT

1979 ◽  
Vol 80 (1) ◽  
pp. 111-116 ◽  
Author(s):  
S. N. JUSTO ◽  
A. NEGRO-VILAR
Keyword(s):  
Sexual Difference ◽  
Female Rats ◽  
Male Rats ◽  
Ovariectomized Rats ◽  
Serum Concentrations ◽  
Control Male ◽  
Male And Female Rats ◽  
Series Of Experiments ◽  
And Control ◽  
Intact Rats

A marked sexual difference in the rise of serum gonadotrophin concentrations after gonadectomy has been described in the rat. Gonadectomy in males induced a rapid rise in the concentrations of both LH and FSH within 8 to 12 h, whereas ovariectomy invoked a rapid increase in the concentration of FSH while the response by LH was delayed for several days. To determine whether these differences could be explained, at least in part, by the different steroid milieu at the time of gonadectomy, a series of experiments were performed to analyse the rise in both LH and FSH serum concentrations in control male and female rats and in male rats that had been pretreated with oestradiol-17β. Adult male rats received an s.c. implant of a silicone elastomer capsule filled with crystalline oestradiol-17 β. Controls received empty capsules. Twenty-four hours later, the oestradiol-implanted rats were castrated and control animals were sham-operated. Both LH and FSH levels remained within control levels after castration in the oestradiol-implanted rats, indicating that the oestradiol implant was preventing any rise of either gonadotrophin. On day 5 after implantation, the capsules were removed, sham-implanted animals were castrated and LH and FSH levels at 12, 24, 48 and 72 h were measured and compared with those of ovariectomized rats at similar intervals. The control male rats displayed the pattern of gonadotrophin increments normally found after castration, with both LH and FSH concentrations rising significantly by 12 h after castration and with further increments at later periods. Oestradiol-treated rats showed a female-like gonadotrophin pattern. FSH levels started to rise significantly at 24 h compared with values from intact rats and increased further at 48 and 72 h. During the first 48 h, FSH levels in both oestradiol-treated, castrated rats and female gonadectomized rats were significantly lower than in castrated animals. LH levels, on the other hand, remained low in both groups during the first 48 h, starting to rise significantly above control levels by 72 h. These results indicate that the different pattern of response to gonadectomy in rats of both sexes may be altered by changes in steroid environment and, therefore, may not be genetically predetermined.

Plasma growth hormone pattern and androgens influence the levels of corticosteroid-binding globulin in rat serum

1989 ◽  
Vol 122 (3) ◽  
pp. 725-732 ◽  
Author(s):  
J.-O. Jansson ◽  
J. Oscarsson ◽  
A. Mode ◽  
E. M. Ritzén
Keyword(s):  
Serum Concentration ◽  
Replacement Therapy ◽  
Polyacrylamide Gel Electrophoresis ◽  
Female Rats ◽  
Male Rats ◽  
Testosterone Replacement Therapy ◽  
Serum Concentrations ◽  
Oestrogen Treatment ◽  
Corticosteroid Binding Globulin ◽  
Hypophysectomized Rats

ABSTRACT The serum concentration of corticosteroid-binding globulin (CBG) is higher in female rats than in males. Combined hypophysectomy and gonadectomy of female rats reduced the serum concentration of CBG as measured by steady-state polyacrylamide gel electrophoresis, whereas hypophysectomy of male rats increased serum CBG. These effects were seen despite replacement therapy with thyroxine and glucocorticoids. Moreover, neither androgen nor oestrogen treatment affected the serum concentrations of CBG in hypophysectomized rats. Continuous infusions of human or bovine GH (1·4 U/kg per day), by means of osmotic minipumps for 1 week, increased serum concentrations of CBG in both hypophysectomized male and female rats. In contrast, intermittent GH replacement therapy by s.c. injections at 12-h intervals either had no effect or suppressed serum CBG levels. In male rats, neonatal (days 1–2) gonadectomy increased CBG levels more than did prepubertal (day 25) gonadectomy, and testosterone replacement therapy reversed these effects. It is concluded that GH increases the serum CBG levels of hypophysectomized rats when it is given in a continuous manner, but not when given intermittently. The sex difference in serum CBG levels of normal rats may, therefore, be attributed to the more continuous secretory pattern of GH previously observed in female rats. Journal of Endocrinology (1989) 122, 725–732

Pituitary-gonadal function in neonatal and adult female rats treated with gonadotropin-releasing hormone agonist and antagonist: short- and long-term effects

1993 ◽  
Vol 129 (3) ◽  
pp. 251-259 ◽  
Author(s):  
E Trimiño ◽  
L Pinilla ◽  
E Aguilar
Keyword(s):  
Reproductive Function ◽  
Chronic Administration ◽  
Ovarian Failure ◽  
Female Rats ◽  
Reproductive Capacity ◽  
Vaginal Opening ◽  
Serum Concentrations ◽  
Long Term Effects ◽  
Releasing Hormone ◽  
Adult Females

We have analyzed the mechanisms involved in ovarian failure after administration of gonadotropin hormone-releasing hormone agonists (GnRH-A) or antagonists (GnRH-ANT). Ovarian and uterine weights, serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol and pituitary FSH and LH contents were measured in Wistar female rats injected from 1–15 or 90–104 days of age with the agonist d-Ala6-d-Gly10-GnRH or the GnRH-ANT Org. 30276. Vaginal opening, first estrous presentation, vaginal smears and reproductive capacity were also analyzed. In both neonatal and adult females GnRH-A induced pituitary desensitization and reduced ovarian and uterine weights and estradiol serum concentrations. Therefore, serum gonadotropin concentrations were increased in adults and decreased in neonatal females. Puberty occurrence and reproductive function remain unaltered after neonatal treatment with GnRH-A. In neonatal females, FSH and LH pituitary content and FSH serum concentrations decreased at the end of treatment with GnRH-ANT. The effects on LH and estradiol secretion depended on the pattern of treatment. Interestingly enough, both vaginal opening and first estrous presentation were precipitated by GnRH-ANT administration. Normal reproductive function was observed in adults. We conclude that: (i) pituitary desensitization of receptors occurred in both neonatal and adult females after chronic administration of GnRH-A; (ii) the ovarian failure observed in adults that is accompanied by increased serum concentrations of gonadotropins was probably due to an inhibitory effect of GnRH-A directly on the ovaries; (iii) the blockade of GnRH action shortly after birth with GnRH-ANT precipitated the onset of puberty; possibly the antagonist blocks some suppressive effects of endogenous LHRH; (iv) the effects of neonatal administration of GnRH-A or GnRH-ANT were transitory.

Adaptive changes of mesenteric arteries in pregnancy: a meta-analysis

2012 ◽  
Vol 303 (6) ◽  
pp. H639-H657 ◽  
Author(s):  
Joris van Drongelen ◽  
Carlijn R. Hooijmans ◽  
Frederik K. Lotgering ◽  
Paul Smits ◽  
Marc E. A. Spaanderman
Keyword(s):  
Arterial Compliance ◽  
Meta Analysis ◽  
Late Pregnancy ◽  
Normal Pregnancy ◽  
Late Gestation ◽  
Mesenteric Arteries ◽  
Sprague Dawley ◽  
Receptor Level ◽  
Sprague Dawley Rats ◽  
Flow Mediated Vasodilation

The vascular response to pregnancy has been frequently studied in mesenteric artery models by investigating endothelial cell (EC)- and smooth muscle cell (SMC)-dependent responses to mechanical (flow-mediated vasodilation, myogenic reactivity, and vascular compliance) and pharmacological stimuli (G protein-coupled receptor responses: GqEC, GsSMC, GqSMC). It is unclear to what extent these pathways contribute to normal pregnancy-induced vasodilation across species, strains, and/or gestational age and at which receptor level pregnancy affects the pathways. We performed a meta-analysis on responses to mechanical and pharmacological stimuli associated with pregnancy-induced vasodilation of mesenteric arteries and included 55 (188 responses) out of 398 studies. Most included studies (84%) were performed in Wistar and Sprague-Dawley rats (SDRs) and compared late gestation versus nonpregnant controls (80%). Pregnancy promotes flow-mediated vasodilation in all investigated species. Only in SDRs, pregnancy additionally stimulates both vasodilator GqEC sensitivity (EC50 reduced by −0.76 [−0.92, −0.60] log[M]) and GsSMC sensitivity (EC50 reduced by −0.51 [−0.82, −0.20] log[M]), depresses vasopressor GqSMC sensitivity (EC50 increase in SDRs by 0.23 [0.16, 0.31] log[M]), and enhances arterial compliance. We conclude that 1) pregnancy facilitates flow-mediated vasodilation at term among all investigated species, and the contribution of additional vascular responses is species and strain specific, and 2) late pregnancy mediates vasodilation through changes at the receptor level for the substances tested. The initial steps of vasodilation in early pregnancy remain to be elucidated.

scholarly journals Behavioural multigenerational effects induced by the administration of very low doses of zinc during pregnancy, lactation, and prepuberal period in the rat

2021 ◽  
Vol 9 (1) ◽  
pp. 72-80
Author(s):  
Silvia G. Ratti ◽  
Osvaldo J. Sacchi ◽  
Edgardo O. Alvarez
Keyword(s):  
Social Activity ◽  
Behavioral Responses ◽  
Chronic Administration ◽  
Female Rats ◽  
Male Rats ◽  
Experimental Setup ◽  
Low Doses ◽  
Next Generation ◽  
Intergenerational Effect ◽  
Multigenerational Effects

In studies from this laboratory, the chronic administration of ZnTe during pregnancy, lactation, and prepuberal stages of litter (F1 generation) modified the behavioral patterns of motivated exploration, lateralized exploration, social activity, and survival responses of maturing rats. To determine whether these affected behaviors would extend to the next generation, F1 litter rats previously exposed to tellurium (Te) up to 30-day-old were left at rest with no further treatment up to 90-day-old. Then, F1 female rats were mated with normal untreated male rats, and in the next generation (F2), the litter rats at 30-day-old preserved the modified behaviors previously observed in their parents. The study revealed that Te effects were intergenerational. Here, considering that ZnTe was used in the previous study and that Zn ion has many physiological functions in the cell, experiments were conducted to elucidate if Zn would have an intergenerational effect similar to Te. Working with the same experimental setup as in the previous study but using ZnCl2 instead of ZnTe, results revealed that none of the behavioral responses studied were affected by the F1 generation. However, in the F2 generation, lateralized exploration and survival behavior were inhibited, suggesting that Zn also has an intergenerational effect.

Evaluation of the Effect of Subchronic Administration of the 70% Ethanol Extract of Millettiea ferruginea (Hochst) Bak (Fabaceae) Seeds on Biochemical, Haematological and Histopathological Parameters in Albino Wistar Rats

2020 ◽  
Vol 36 (1) ◽  
pp. 49-60
Author(s):  
Mekonnen Debebe ◽  
Molla Getu ◽  
Mekbeb Afework ◽  
Aster Tsegaye ◽  
Eyasu Makonnen ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Haemoglobin Concentration ◽  
Ethanol Extract ◽  
Chronic Administration ◽  
Female Rats ◽  
Male Rats ◽  
Albino Rats ◽  
Blood Levels ◽  
Male And Female Rats ◽  
Wistar Albino Rats

Millettiea ferruginea (Hochst) Bak (Fabaceae) is an indigenous plant, traditionally used for the treatment of various disease conditions in Ethiopia  without substantiating its safety. This study, therefore, evaluated its toxicity in albino Wistar rats. The hydroalcoholic extract of M. ferruginea was prepared by maceration of the powdered seeds in 70% ethanol. The effect of extract administration to albino Wistar albino rats for 90 days at doses of 125 mg/kg and 250 mg/kg b/w was investigated. Subchronic administration of the extract at a dose of 250 mg/kg decreased mean corpuscular haemoglobin concentration (MCHC) and monocytes in female rats. The blood levels of alkaline phosphatase (ALP), alanine transaminase (ALT), creatine kinase (CK) and urea in the female, and CK in male rats treated with the extract at 250 mg/kg were significantly increased. Histopathological investigation of the liver revealed signs of blood congestions in portal vein and hepatic artery at 125 mg/kg, and minor inflammation, congestions and focal hepatocellular necrosis at 250 mg/kg in both sexes. The extract produced atrophy of the glomeruli, widened urinary space andinflammation of the kidney at both doses, and also caused minor tubular necrosis and peritubular blood congestions at 250 mg/kg in both male and female rats. In the heart of extract treated rats, there were congestions of blood vessels and necrosis of myocardium at both doses, and inflammation at 250 mg/kg. Desquamation and infiltration of the mucosa at both doses, and submucosal atrophy at 125 mg/kg and blood congestions at 250 mg/kg were observed in the small intestine of extract treated rats. The present findings suggest that the extract is relatively safe at therapeutic dose, although some signs of toxicity occurred mainly at the higher dose in female rats. Additional investigations on chronic administration of the extract is recommended to further substantiate the safety of the plant. Keywords: Millettia ferruginea, ethanol seed extract, toxicity, histopathology, Wistar albino rats 

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