Parameters In Male Rats Research Articles

Single Photon Emission Computed Tomography Demonstrated Efficacy of 17β-Estradiol Therapy in Male Rats After Trauma-Hemorrhage and Extended Hypotension

This study evaluated the effect of 17β-estradiol (E2) administration on cardiovascular parameters in male rats after trauma-hemorrhage and for an extended period (3 hours) of severe hypotension, based on blood-pool single photon emission computed tomography imaging. After a 5-cm midline laparotomy, male Sprague-Dawley rats were injected intravenously with Tc-bovine serum albumin; the animals were then bled for >45 minutes to reach maximum bleedout (MBO; removal of 60% of the circulating blood volume). E2 (1 mg/kg body weight, 0.4 mL/kg) or vehicle (cyclodextrin [CD], 0.4 mL/kg) was injected intravenously at MBO; no additional fluid was administered for 3 hours. Imaging was performed continually for a maximum of 3 hour post-MBO. The percentages of injected dose in heart, brain, liver, and kidney were quantified from the imaging (n = 8/group) at 0 minutes, 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, and 180 minutes post-MBO. Mixed model analysis of variance was used to analyze the difference between the two groups over six imaging time points (30-180 minutes post-MBO). The percentages of injected dose of Tc-bovine serum albumin in heart, kidney, and liver after E2 administration were significantly higher than those after CD administration (p = 0.036, 0.025, and 0.028 for heart, kidney, and liver, respectively), whereas those in brain were not different between E2 and CD administration (p = 0.343). The significantly larger blood volume maintained in heart, kidney, and liver of rats after E2 therapy compared with control supports the notion that E2 produces salutary effects on the cardiovascular system after trauma-hemorrhage and even extended periods of severe hypotension.

Modulatory effects of chronic ethanol ingestion on hepatotoxicity-related parameters in male rats

5 g of ethanol (20% w/v) per kg body weight was administered to ten rats weighing between 166 – 170 grams daily for 28 days along side with normal feeds and water ad libitum. The administration of ethanol was done orally using oral catheter. A control group o ten rats was set up for a proper experimental evaluation. Analysis at the end of the adminstration showed tha ethanol in a dose of 5g/kg body weight significantly modulates (P Keywords: Rats, Ethanol, Oral administration, Catheter, Liver, Hepatotoxicity, Antioxidant enzyme

Neonatal Handling Impairs Spatial Memory and Leads to Altered Nitric Oxide Production and DNA Breaks in A Sex Specific Manner

Early life events lead to behavioral and neurochemical changes in adulthood. The aim of this study is to verify the effects of neonatal handling on spatial memory, nitric oxide (NO) production, antioxidant enzymatic activities and DNA breaks in the hippocampus of male and female adult rats. Litters of rats were non-handled or handled (10 min/day, days 1-10 after birth). In adulthood they were subjected to a Morris water maze or used for biochemical evaluations. Female handled rats showed impairment in spatial learning. They also showed decreased NO production, while no effects were observed in these parameters in male rats. No effects were observed on the number of hippocampal NADPH diaphorase positive cells. In the Comet Assay, male handled rats showed increased DNA breaks index when compared to non-handled ones. We conclude that neonatal handling impairs learning performance in a sex-specific manner, what may be related to NO decreased levels.

Comparative Toxicological Evaluation of Phthalate Diesters and Metabolites in Sprague-Dawley Male Rats for Risk Assessment

In order to comparatively assess the systemic toxicity and sperm parameters, nine phthalate diesters, including di(2-ethylhexyl) phthalate (DEHP), di(n-butyl) phthalate (DBP), di-n-octyl phthalate (DnOP), diethyl phthalate (DEP), butylbenzyl phthalate (BBP), dimethyl phthalate (DMP), di-isodecyl phthalate (DIDP), diundecyl phthalate (DUP), and di-isononyl phthalate (DINP), and five phthalate monoesters, including mono(2-ethylhexyl) phthalate (MEHP), monobutyl phthalate (MBuP), monobenzyl phthalate (MBeP), monoethyl phthalate (MEP), monomethyl phthalate (MMP), and phthalic acid (PA) were administered orally to Sprague-Dawley male rats at 250 (phthalate monoesters and PA) or 500 mg/kg body weight (bw)/d (phthalate diesters) for 4 wk. Liver weights were significantly increased in g roups treated with DEHP, DBP, BBP, DIDP, DINP, MEHP, and MBuP compared to the control. Testes weights were significantly reduced only in DEHP, DBP, and MEHP-treated groups compared to the control. Significant decreases in red blood cell (RBC) and hematocrit (Ht) levels were observed in DEHP-treated rats, whereas significant increases in mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and platelet (PLT) levels were found in the DEHP-treated group. Hemoglobin (Hb) level was reduced only in the DMP group. Similar to effects on testis and epididymal weights, DEHP and MEHP significantly reduced sperm numbers and motility. In particular, DnOP, DBP, BBP, MEP, MBuP, DUP, DINP, and MBeP significantly lowered the sperm counts and sperm motility of epididymal sperm, detected by a change in the sperm motion parameters. The strongest to the weakest adverse effects for sperm motility were as follows: DEHP > DBP > DnOP > DUP > DIDP > BBP among diesters and MBuP > MEP > MEHP among monoesters, respectively. These results suggest that the adverse effects of phthalate esters (PEs) on sperm parameters in male rats are greater with phthalate diesters than monoesters, which may be useful for the risk assessment of phthalates.

Effects of ethanol and/or chloroquine with low protein dietary intake on some biochemical parameters in male rats.

In malaria-endemic developing countries, plagued with malnutrition, patients undergoing chloroquine (Q) treatment on prolonged basis often consume ethanol (E) regularly. This may constitute a serious health problem. The objective of this study was to investigate whether concurrent administration of E and Q under conditions of protein malnutrition may impact negatively on biochemical parameters. An experimental study was conducted to investigate biochemical effects of E and/or Q associated with protein malnutrition in adult male Sprague Dawley rats. Two groupsof adult male Sprague-Dawley rats were fed either normal protein diet (NP, 15%) or low protein diet (LP, 6%). Each diet group includes the controls (NPC, LPC), chloroquine- (Q); [NPQ; LPQ], ethanol- (E); [NPE; LPE} or both chloroquinine and ethanol (NPEQ; LPEQ) treated groups. Chloroquine diphosphate (10mg, kg-1 body weight per rat) was administered intramuscularly, on days 0, 10, 20, and 30 to appropriate groups, while 6% E in drinking water was provided ad libitum to Etreated groups. Drinking water was given to Q-treated groups, and physiological saline was injected to E-treated groups. After 40 days, blood was collected, underether anesthesia, by cardiac puncture for biochemical analysis. Results showed that concurrent treatment of E and Q slightly decreased TP and albumin (Alb) levels in LPEQ-rats compared to LPC, LPE and LPQ rat groups. Furthermore, TP level was substantially and significantly elevated in NPEQ-rats compared to LPEQ, NPE and NPQ rat groups. Ethanol and Chloroquine interaction exacerbated ALP and ALT activities in LPEQ-rats compared to NPEQ- rats. Urea depression was enhanced inLPEQ- than in NPEQ-rats. Creatinine levels were increased in all treatment groups. The results suggest increased toxic effect of concurrent intake of E and Q in LP- fed rats. The findings show that LP dietary intake potentiates adverse effects of combined E and Q. This has implications for clinical practice, especially in poor malaria endemic countries where prevalence of protein malnutrition is often high, and patients who consume alcohol while on chloroquine, are at greater risk of severe toxic effectof combined E and Q intake.

Propolis alleviates aluminium-induced lipid peroxidation and biochemical parameters in male rats

Aluminium is present in many manufactured foods and medicines and is also added to drinking water during purification purposes. Therefore, the present experiment was undertaken to determine the effectiveness of propolis in alleviating the toxicity of aluminium chloride (AlCl3) on biochemical parameters, antioxidant enzymes and lipid peroxidation of male Wistar Albino rats. Animals were assigned to 1 of 4 groups: control; 34mg AlCl3/kg bw; 50mg propolis/kg bw; AlCl3 (34mg/kg bw) plus propolis (50mg/kg bw), respectively. Rats were orally administered their respective doses daily for 70days. The levels of thiobarbituric acid reactive substances (TBARS) was increased, and the activities of glutathione S-transferase, superoxide dismutase, catalase and glutathione peroxidase were decreased in liver, kidney and brain of rats treated with AlCl3. While, TBARS was decreased and the antioxidant enzymes were increased in rats treated with propolis alone. Plasma transaminases, lactate dehydrogenase, glucose, urea, creatinine, bilirubin, total lipid, cholesterol, triglyceride and LDL-c were increased, while total protein, albumin and high HDL-c were decreased due to AlCl3 administration. The presence of propolis with AlCl3 alleviated its toxic effects in rats treated with AlCl3. It can be concluded that propolis has beneficial influences and could be able to antagonize AlCl3 toxicity.

Toxoplasma gondii: Reproductive parameters in experimentally infected male rats

Toxoplasma gondii is a protozoan parasite that is globally widespread and infects man and animals. With the aim of studying the influence of toxoplasmosis on male reproductive parameters, we investigated sperm motility, concentration and morphology of male rats experimentally infected by T. gondii. The GT F1 strain of T. gondii tissue cysts were fed at a dose of 5 × 10 3 tissue cysts per rat by oral gavage in an experimental group of 42 healthy adult male Wistar rats, while 42 male rats were used as controls. On days 10, 20, 30, 40, 50 and 60 post-inoculation (p.i.) 7 rats from each group were anesthetized. The body weight of each animal was recorded, then epididymis and testes were immediately removed, weighed and semen evaluation was undertaken. Weight of the right epididymis was significantly decreased on day 30 p.i., sperm motility was significantly decreased on days 10, 20, 30, 40, 50 and 60 p.i. and sperm concentration was significantly decreased on days 10, 30, 40 and 60 p.i. A marked increase of sperm abnormalities was noticed on days 30 and 40 p.i. No pathological lesions were detected either in the pituitary gland or the testes. In this study it was found that toxoplasmosis can affect main reproductive parameters in male rats, which are the most predictive of their fertilizing capacity.

Impact of Ovarian Hormones on the Modulation of the Serotonin Transporter by Fluvoxamine

Most preclinical studies examining the mechanism(s) of action of antidepressants are carried out using male animals. Blockade of serotonin transporter (SERT) function by selective serotonin reuptake inhibitors (SSRIs) is the initial event that triggers a not completely understood process that results in clinical improvement in depression. To investigate whether there are differences in the ability of SSRIs to inhibit the SERT between male and female rats at different phases of the estrous cycle, clearance of locally applied serotonin (5-HT) was measured by in vivo chronoamperometry. Local application of the SSRI, fluvoxamine, directly into the CA3 area of hippocampus increased significantly 5-HT clearance time parameters in male rats and female rats in estrus or diestrus, but not in proestrus. The contribution of ovarian steroids to this result was investigated in ovariectomized (OVX) rats treated with estradiol benzoate (EB) and/or progesterone (P). In OVX-control rats, fluvoxamine increased clearance time parameters, whereas EB and/or P treatment blocked this effect, consistent with what was seen in female rats in proestrus. This effect was gender-specific, since treatment of castrated rats with EB/P had no effect on the ability of fluvoxamine to slow 5-HT clearance. The time course of hormonal effects showed that 1-60 min after local application of 17-beta-estradiol (E(2)) into the CA3 region of OVX rats, fluvoxamine had no effect on clearance time of 5-HT. E(2)-BSA mimicked E(2)'s effects at 10 min but not at 60 min. Pretreatment with estrogen receptor antagonists blocked the effects of E(2). The finding that acutely both estradiol and progesterone can inhibit the ability of an SSRI to slow the clearance of 5-HT, may have important implications for the use of SSRIs in women.

Biochemical and Haematological Study in Rats Exposed to Cadmium Chloride in Drinking Water

The objective of this study was investigate the Physiological effect ofdifferent concentrations of cadmium chloride in drinking water on somebiochemical and haematological parameters of male rats. Animals in thisexperiment were randomly divided into four equal groups and treated for 15weeks as follows : Rats in control group were offered ordinary tap water ,while animal in M1 , M2 , and M3 were received 10 , 20 , 30 ppm Cdcl2 indrinking water, respectively. The activity of Alanine aminotransferase(ALP), Aspartate aminotrasferase (AST) and alkaline phosphatase (ALP) inserum were measured. Further mor, hemoglobin concentration (Hb) andwhite blood cells count (WBCs) were detected. The result revealed thataddition of cadmium chloride in different concentrations in drinking watercaused a significant increase in activity of serum of ALT in treated group(M1 , M2 , M3 ) as compound with control. Within the time the activity ofserum AST was significantly increased in three treated group as comparedwith pretreatment period. On the other hand , significant increase in serumALP concentration were show in both M1 and M3 treated groups at 12th and15th week of the treatment as compared with control group. Significantdecrease in haemoglobin concentration were observed in M1 , M2 , M3 from9th week to the end of experiment comparing to control. While cadmiumchloride treatment caused significant increase in total white blood cells countin treated groups as compared with control group. On Conclusion, it seemslikely that exposure of male rats to cadmium chloride at level above thepermissive one had induced clear biochemical and haematological changes.

Neonatal hyperleptinaemia programmes adrenal medullary function in adult rats: effects on cardiovascular parameters

Epidemiological studies have shown a strong correlation between stressful events (nutritional, hormonal or environmental) in early life and development of adult diseases such as obesity, diabetes and cardiovascular failure. It is known that gestation and lactation are crucial periods for healthy growth in mammals and that the sympathoadrenal system is markedly influenced by environmental conditions during these periods. We previously demonstrated that neonatal hyperleptinaemia in rats programmes higher body weight, higher food intake and hypothalamic leptin resistance in adulthood. Using this model of programming, we investigated adrenal medullary function and effects on cardiovascular parameters in male rats in adulthood. Leptin treatment during the first 10 days of lactation (8 microg 100 g(-1) day(-1), s.c.) resulted in lower body weight (6.5%, P < 0.05), hyperleptinaemia (10-fold, P < 0.05) and higher catecholamine content in adrenal glands (18.5%, P < 0.05) on the last day of treatment. In adulthood (150 days), the rats presented higher body weight (5%, P < 0.05), adrenal catecholamine content (3-fold, P < 0.05), tyrosine hydroxylase expression (35%, P < 0.05) and basal and caffeine-stimulated catecholamine release (53% and 100%, respectively, P < 0.05). Systolic blood pressure and heart rate were also higher in adult rats (7% and 6%, respectively, P < 0.05). Our results show that hyperleptinaemia in early life increases adrenal medullary function in adulthood and that this may alter cardiovascular parameters. Thus, we suggest that imprinting factors which increase leptin and catecholamine levels during the neonatal period could be involved in development of adult chronic diseases.

Negative effects of nicotine on bone-resorbing cytokines and bone histomorphometric parameters in male rats

The effects of nicotine administration on bone-resorbing cytokines, cotinine, and bone histomorphometric parameters were studied in 21 Sprague-Dawley male rats. Rats aged 3 months and weighing 250-300 g were divided into three groups. Group 1 was the baseline control (BC), which was killed without treatment. The other two groups were the control group (C) and the nicotine-treated group (N). The N group was treated with nicotine 7 mg/kg body weight and the C group was treated with normal saline only. Treatment was given by intraperitoneal injection for 6 days/week for 4 months. The rats were injected intraperitoneally with calcein 20 mg/kg body weight at day 9 and day 2 before they were killed. ELISA test kits were used to measure the serum interleukin-1 (IL-1), interleukin-6 (IL-6), and cotinine (a metabolite of nicotine) levels at the beginning of the study and upon completion of the study. Histomorphometric analysis was done on the metaphyseal region of the trabecular bone of the left femur by using an image analyzer. Biochemical analysis revealed that nicotine treatment for 4 months significantly increased the serum IL-1, IL-6, and cotinine levels as compared to pretreatment levels. In addition, the serum cotinine level was significantly higher in the N group than in the C group after 4 months treatment. Histomorphometric analysis showed that nicotine significantly decreased the trabecular bone volume (BV/TV), trabecular thickness (Tb.Th), double-labeled surface (dLS/BS), mineralizing surface (MS/BS), mineral appositional rate (MAR), and bone formation rate (BFR/BS), while causing an increase in the single-labeled surface (sLS/BS), osteoclast surface (Oc.S/BS), and eroded surface (ES/BS) as compared to the BC and C groups. In conclusion, treatment with nicotine 7 mg/kg for 4 months was detrimental to bone by causing an increase in the bone resorbing cytokines and cotinine levels. Nicotine also exerted negative effects on the dynamic trabecular histomorphometric parameters.

Short‐Term Effects of Adolescent Methylphenidate Exposure on Brain Striatal Gene Expression and Sexual/Endocrine Parameters in Male Rats

Exposure to methylphenidate (MPH) during adolescence is the elective therapy for attention deficit/hyperactivity disorder (ADHD) children, but raises major concerns for public health, due to possibly persistent neurobehavioral changes. Rats (30- to 44-days old) were administered MPH (2 mg/kg, i.p once daily) or saline (SAL). At the end of the treatment we collected plasma, testicular, liver, and brain (striatum) samples. The testes and liver were used to evaluate conventional reproductive and metabolic endpoints. Testes of MPH-exposed rats weighed more and contained an increased quantity of sperm, whereas testicular levels of testosterone (TST) were markedly decreased. The MPH treatment exerted an inductive effect on enzymatic activity of TST hydroxylases, resulting in increased hepatic TST catabolism. These findings suggest that subchronic MPH exposure in adolescent rats could have a trophic action on testis growth and a negative impact on TST metabolism. We have analyzed striatal gene expression profiles as a consequence of MPH exposure during adolescence, using microarray technology. More than 700 genes were upregulated in the striatum of MPH-treated rats (foldchange >1.5). A first group of genes were apparently involved in migration of immature neural/glial cells and/or growth of novel axons. These genes include matrix proteases (ADAM-1, MMP14), their inhibitors (TIMP-2, TIMP-3), the hyaluronan-mediated motility receptor (RHAMM), and growth factors (transforming growth factor-beta3 [TGF-beta3] and fibroblast growth factor 14 [FGF14]). A second group of genes were suggestive of active axonal myelination. These genes mediate survival of immature cells after contact with newly produced axonal matrix (laminin B1, collagens, integrin alpha 6) and stabilization of myelinating glia-axon contacts (RAB13, contactins 3 and 4). A third group indicated the appearance and/or upregulation of mature processes. The latter included genes for: K+ channels (TASK-1, TASK-5), intercellular junctions (connexin30), neurotransmitter receptors (adrenergic alpha 1B, kainate 2, serotonin 7, GABA-A), as well as major proteins responsible for their transport and/or anchoring (Homer 1, MAGUK MPP3, Shank2). All these genes were possibly involved in synaptic plasticity, namely the formation, maturation, and stabilization of new neural connections within the striatum. MPH treatment seems to potentiate synaptic plasticity, which is an age-dependent developmental phenomenon that adolescent rats are very likely to show, compared to adults. Our observations suggest that adolescent MPH exposure causes only transient changes in reproductive and hormonal parameters, and a more enduring enhancement of neurobehavioral plasticity.

홍삼유출액으로부터 분리한 조사포닌이 TCDD (2,3,7,8-Tetrachlorodibenzo-ρ-dioxin)로 급성독성을 유도한 흰쥐의 혈액 생화학지수에 미치는 영향

본 연구는 랫드에서 2,3,7,8-tetrachlorodibenzo--dioxin (TCDD)로 유도된 급성독성에 대한 홍삼유출액으로부터 분리한 조사포닌의 방어효과를 조사하기 위해 수행되었다. 40마리의 웅성 랫드를 4군으로 나누어 정상군에 대해서는 TCDD의 운반체를, TCDD 단독투여군 (TT)에게는 TCDD(<TEX>$5{\mu}g/ml$</TEX>)와 생리식염수를 1회 복강주사하였다. 한편, 조사포닌 투여군 (RGE-CS20, RGE-CS40)은 조사포닌을 각각 20 및 40 mg/kg,b.w/day의 용량으로 TCDD 투여 1주 전부터 총 4 주간 복강주사하였다. TCDD 단독투여군의 체중은 TCDD투여 1주째부터 유의하게 감소한 반면, 조사포닌 투여군은 TCDD 단독투여군에 비해 완만하기는 하지만 유의하게 증가하여 체중감소가 억제되었다. 조사포닌 투여군은 TCDD독성에 의해 증가한 TG, TC, LDL, AST ALT, <TEX>$Fe^{2+}$</TEX> 함량은 감소시켰고, TCDD 독성에 의해 감소된 glucose, amylase, LDH, CK 활성을 증가시켜 혈액 임상화학지수를 유의하게 개선시키는 것으로 나타났다. 이상의 결과로부터 홍삼유출액으로부터 분리한 조사포닌은 TCDD에 의해 주도된 체중감소와 장기 기능저하에 대해서 현저한 방어효과를 나타낸다는 사실을 알 수 있었다. This study was carried out to investigate the protective effect of crude saponin from red ginseng efflux (RGE-CS) on biochemical parameters in male rats acutely exposed to 2,3,7,8-tetrachlorodibenzo-<TEX>$\rho$</TEX>-dioxin (TCDD). Forty male rats (<TEX>$200{\pm}20g$</TEX>) were divided into 4 groups. Normal control group (NC) received vehicle and saline; only TCDD-treated group (TT) received TCDD (<TEX>$5{\mu}g/kg$</TEX>, single dose) intrperitoneally; RGE-CS 20 received 20 mg/kg of crude saponin i.p. for 4 weeks from 1 week before TCDD-exposure; RGE-CS 40 also received 40 mg/kg of crude saponin i.p. for 4 weeks from 1 week before TCDD-exposure. Body weight of TT group was significantly decreased after TCDD-exposure. However, body weight of crude saponin groups increased throughout the experimental period, although the increasing rate was slower than that of NC group. Decrease in body weight was not observed during the experimental period in RGE-CS 40. Increases in triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), AST, ALT and <TEX>$Fe^{2+}$</TEX> levels by TCDD intoxication were significantly attenuated by the RGE-CS treatment. Decrease in glucose, amylase, lactate dehydrogenase (LDH) and creatinine kinase (CK) by TCDD also were inhibited by the RGE-CS. These results suggest that saponin from red-ginseng efflux might be a useful protective agent against TCDD, an endocrine disrupter.

Evalution of the castrated male Sprague–Dawley rat as a model of the metabolic syndrome and type 2 diabetes

Low testosterone levels have been shown to be predictive for the development of the metabolic syndrome in men. The aim of this study was to describe effects of testosterone deficiency on metabolic syndrome-related parameters in male rats in order to evaluate the rat as a model for the human metabolic syndrome related to low testosterone levels. Male Sprague-Dawley rats were castrated or sham operated at 16 weeks of age and fed either a standard or a high energy diet. Measured parameters were: food intake, body weight, fat distribution, energy expenditure, physical activity and blood/plasma parameters related to glucose and lipid metabolism. Castration led to an increase in the amount of subcutaneous fat, but did not result in any changes in the visceral fat. Fasting blood glucose levels were increased and free fatty acids concentration decreased in the castrated rats from 2 weeks after castration and throughout the study, whereas no significant differences between the groups were found in any of the other parameters measured. A high-energy diet did not change the response to castration in male Sprague-Dawley rats. Compared to humans rats respond differently to testosterone deficiency. Only few of the features typical for the human metabolic syndrome were observed in castrated male Sprague-Dawley rats. Therefore, we conclude that with the present experimental setup the castrated rat is not an optimal model for studies on the influence of testosterone deficiency on body fat distribution and the development of other central components of the metabolic syndrome.

Comparison of dexamethasone pharmacokinetics in female rats after intravenous and intramuscular administration

This study seeks a route of drug administration that would produce a pharmacokinetic profile for dexamethasone not significantly different from the intravenous route in female rats and would offer reproducible drug input with minimal stress to the animals. The intramuscular (i.m.) route of drug administration vs intravenous (i.v.) injection were compared in three female Wistar rats administered 1 mg/kg dexamethasone phosphate. Dexamethasone plasma concentrations were measured by a normal phase HPLC assay for 12 h after drug administration. Dexamethasone exhibited monoexponential behavior after intravenous dosing and was absorbed rapidly after intramuscular dosing (absorption half-life of 14 min) with 86% bioavailability. Dexamethasone had a terminal half-life of 2.3 h after drug administration by either route. The volume of distribution of 0.78 l/kg and the clearance of 0.23 l/h/kg are in good agreement with reported pharmacokinetic parameters in male rats. Intravenous dosing can be replaced by intramuscular dosing without causing any marked difference in dexamethasone pharmacokinetics.

Lepidium meyenii Walp. improves sexual behaviour in male rats independently from its action on spontaneous locomotor activity

Lepidium meyenii Walpers (Maca) is traditionally employed in the Andean region for its supposed properties to improve energy and fertility. The aim of this study was to evaluate the effect of acute and chronic Maca pulverised root oral administration on rat sexual behaviour. Sixty male sexually experienced rats (20 group) were daily treated for 15 days with Maca 15 mg kg −1, Maca 75 mg kg −1 or saline 0.5 ml kg −1. The following sexual performance parameters were evaluated at first and last day of treatment: 1st mount (ML), 1st intromission (IL), ejaculation (EL) and postejaculatory (PEL) latencies, intercopulatory interval (ICI) and copulatory efficacy (CE). An activity cage test was carried out to evaluate if Maca-induced locomotion changes could indirectly improve rat sexual performances. It was observed that both lower and higher Maca doses acutely decreased ML, IL and ICI in a significant way ( P<0.05), while only the 75 mg kg −1 dose decreased the PEL ( T=29, P<0.05). This effect seems to be the only one dose-dependent. After 15 days of treatment, both doses are able to significantly decrease ML, IL, EL and PEL, while the 75 mg kg −1 dose decreased the ICI ( T=40, P<0.05) too. IL, EL and PEL variations seem to be dose-related after chronic treatment. Moreover, chronic Maca treatment induced an apparently not dose-related increase in rat locomotion, during the second 10-min period of observation in the activity cage. The late in Maca-induced locomotion modification excludes that improvement of tested sexual performance parameters is related to an increase in rat aspecific activity. Thus, it was concluded that both acute and chronic Maca oral administration significantly improve sexual performance parameters in male rats.

Diethylstilbestrol-treated adult rats with altered epididymal sperm numbers and sperm motility parameters, but without alterations in sperm production and sperm morphology.

In this study, we characterized estrogenic effects of diethylstilbestrol (DES) on reproductive parameters in male rats to identify a minimal dose level that alters epididymal and sperm functions but has little or no effect on sperm production and/or spermatogenesis. Adult rats (five animals/group) received s.c. injections of 0.2 ml of corn oil containing DES at a rate of 1.0 mg, 200 microg, 40 microg, 8 microg, 1.6 microg, or 320 ng x rat(-1) x day(-1) for 12 days. The control group received corn oil only. DES effects were similar in the 8-microg group and higher dose groups and included significant (P < or = 0.05) reductions in 1) absolute and relative weights of the head and body of the epididymis (EP), tail of the EP, and seminal vesicle, 2) numbers of sperm in both regions of the EP, and 3) motility characteristics in sperm collected from the tail of the EP. Conversely, no significant changes were observed in relative testis weight, daily sperm production, spermatogenesis, seminiferous epithelial height in stage VII, and sperm morphology. All of the above parameters in the 1.6-microg group (except seminal vesicle weight) and 320-ng group were comparable to those of controls. Plasma testosterone (T) level was reduced to an almost undetectable level in the > or = 8-microg groups and to a very low level in the 1.6-microg group (0.35 vs. 2.36 ng/ml in controls or 320-ng group), but LH level was unaltered. In a parallel fertility study, males received DES at a rate of 40, 8, or 1.6 microg x rat(-1) x day(-1) for 12 days prior to and 12 days during cohabitation (1:1) with untreated females. Of the 15 females cohabited with treated males (5 females/dose), none in the 40-microg and 8-microg groups and 1 in the 1.6-microg group formed a copulatory plug and delivered 8 pups, in contrast to 5/5 copulatory plugs and 13-15 pups/litter in the controls. DES at a rate of 8 microg x rat(-1) x day(-1) for 12 days reduced EP weights, sperm numbers in the EP, and sperm motility patterns but caused minimal to no alterations in daily sperm production, spermatogenesis, or sperm morphology. Factors other than T, or in addition to lower T, may be responsible for DES-induced reproductive disorders (despite lower T, sperm contents and sperm motility patterns in the EP were normal in the 1.6-microg group). Deficits in EP sperm functions and/or sexual behavior (as evident from absence of copulatory plugs) probably accounted for reduced fertility in treated males.

Reproductive and developmental toxicity study of gadobenate dimeglumine formulation (E7155) (1)--Fertility study in male rats by intravenous administration

The influence of gadobenate dimeglumine formulation (E7155) on general reproductive performance and fertility in male rats of the Sprague-Dawley strain was assessed in this study. E7155 was administered by intravenous injection at a dosage of 0.3, 1.0, or 2.0 mmol/kg/day to groups of 22 male rats for 13 weeks. Control animals received 0.9% sterile physiological saline throughout the same period. After four weeks of treatment, each male was paired with an untreated female of the same strain. Each male was paired again after 10 weeks of treatment with another untreated female of the same strain. All females were killed on Day 14 of gestation for examination of pregnancy status. No significant toxicological signs associated with systemic exposure to E7155 were observed. There were no effects of treatment with E7155 on body weight gain, food consumption, macroscopic findings, reproductive organ weights and sperm count or sperm motility in male rats. Mating performance after pairing at Weeks 4 and 10 of treatment as well as litter size and number of survival embryos on Day 14 of gestation were not affected by paternal treatment with E7155. From these results, the No Observed Adverse Effect Level (NOAEL) of E7155 was 2.0 mmol/kg/day for general and reproductive toxicity parameters in male rats treated with E7155 and for development in their embryos.

Behavioural and functional neurotoxicological changes caused by cadmium in a three-generational study in rats

1. Three consecutive generations of Wistar rats were orally treated by gavage with 3.5, 7.0 or 14.0 mg/kg cadmium (in form of cadmium chloride diluted in distilled water) over the period of pregnancy, lactation and 8 weeks after weaning. 2. Behavioural (open field behaviour) and electrophysiological (spontaneous and evoked cortical activity, etc.) parameters of male rats from each generation were investigated at the age of 12 weeks. 3. The main behavioural outcomes were change in vertical exploration activity (rearing) and increased exploration of an open field centre. The spontaneous and evoked electrophysiological variables showed dose- and generation-dependent changes (increased frequencies in the electrocorticogram, lengthened latency and duration of evoked potentials, etc.) signalling a change in neural functions. 4. The data show that low-level, multigeneration exposure to inorganic cadmium can affect functions of the nervous system. This suggests that cadmium exposed human populations may be at risk of developing nervous system disorders.

Dietary selenium regulation of glutathione peroxidase mRNA and other selenium-dependent parameters in male rats

Weanling male rats were fed a basal torula yeast diet (0.007 μg Se/g diet) supplemented with graded levels of Se (0 to 0.2 μg Se/g diet as Na 2SeO 3) (three rats/group) to evaluate classical glutathione peroxidase (GPXI, GSH:H 2O 2 oxidoreductase, EC 1.11.1.9) mRNA level as an indicator of intracellular Se status. Growth was followed throughout the dietary treatment and a number of Se-dependent parameters including liver GPX1 mRNA levels were determined after 33 days. Growth was not impaired at any level of dietary Se supplementation. In rats fed the Se-deficient basal diet, liver Se concentration was 5 ± 1%, liver GPX1 mRNA levels were 10 ± 2%, plasma GPX activity was 2 ± 1%, erythrocyte GPX activity was 37 ± 1%, and liver GPX activity was 0 ± 2% of the levels in rats fed 0.1 μg Se/g diet; these parameters increased sigmoidally with increasing dietary Se, showing a breakpoint near 0.1 μg Se/g diet. Graphical analysis indicated that the increase in liver GPX1 mRNA level with increasing dietary Se, preceded the increase in liver GPX activity. Se supplementation had no effect on polyadenylated mRNA levels or on β-actin mRNA levels, demonstrating that Se regulation of GPX1 mRNA is specific. Se-deficient liver selenoprotein P mRNA levels were 69 ± 2% of the levels in rats fed 0.1 μg Se/g diet. We hypothesize that GPX1 mRNA is a primary target of the Se regulatory mechanism, making GPX1 mRNA level a potentially useful indicator of the status of an important intracellular regulatory pool of Se.