Cyclophosphamide-induced testicular toxicity ameliorate by American ginseng treatment: an experimental study

Background: cyclophosphamide [CP] is one of the most invasive chemotherapeutic agents, which used commonly despite of its wide spectrum toxicity. Clinical evidence showed toxic side effects of CP in multiple organ systems

Objective: the objective of the present study was to evaluate the effects of American ginseng on CP-induced testicular toxicity in rats

Materials and Methods: adult male Wistar rats [220 +/- 30 gr] were randomly divided into four groups [n=7 in each]. Group 1 as control received normal saline by gavage, group 2 received CP [6.1 mg/kg/day, i.p.] for a period of 50 days. Group 3 received American ginseng [500 mg/kg/day] by gavage. Group 4 received American ginseng [500 mg/kg/day] 1h prior to the administration of CP in the equal dose of group 2. The animals scarified one day after the last treatment and the effects of American ginseng on the sperm vital parameters, testicular functions, biochemical factors, and structural malformations evaluated

Results: serum testosterone concentration was significantly decreased whereas the level of malondialdehyde and DNA damage were significantly increased in animals of CP group [p<0.01]. Co-administration of American ginseng reversed these parameters and improved recovery in CP+ginseng group. In addition, seminiferous tubules of testis severely damaged in the CP group but ginseng improved histologic changes in CP+ginseng group

Conclusion: the findings confirmed the protective effects of American ginseng on toxicity induced by CP in the reproductive system of male rats

Flavonoids Fraction of Mespilus Germanica Alleviates Insulin Resistance in Metabolic Syndrome Model of Ovariectomized Rats via Reduction in Tumor Necrosis Factor-α

OBJECTIVES: The rate of metabolic syndrome (MetS) in women diagnosed as they age is one of the main concerns of health cares. Recently new strategies used to prevent progressions of MetS toward the diagnosis of diabetes have focused on plant flavonoids. This study was aimed to investigate the beneficial effects of flavonoids fraction of Mespilus germanica leaves (MGL) on MetS in ovariectomized (OVX) rats. METHODS: Twenty-four adult female Wistar rats, weighing 200 to 250 g, were divided into 3 groups: Sham surgery, OVX + Salin, or OVX + Flavonoid. Three weeks after ovariectomy, animals displayed MetS criteria received flavonoid injection (10 mg/kg, intraperitoneally) for 21 days. Then the body weight, body mass index, waist circumference, visceral fat, fasting blood glucose, serum insulin, lipid profiles and tumor necrosis factor-α (TNF-α) were measured. RESULTS: Treatment with flavonoids fraction of MGL significantly decreased serum level of insulin (P = 0.011), glucose (P = 0.024), TNF-α (P = 0.010), also MetS Z score (P = 0.020) and homeostasis model assessment of insulin resistance (P = 0.007). Lipid profiles and visceral fat showed insignificant reduction. CONCLUSIONS: Flavonoids of MGL attenuates some of the MetS components possibly via reduction in TNF-α inflammatory cytokine.

effects of chlorpromazine on reproductive system and function in female rats

Chlorpromazine [CPZ], an antipsychotic drug, is associated with increased risk of sexual dysfunction through increasing prolactin levels. The current study evaluates the effect of CPZ-induced hyperprolactinemia on ovarian follicular growth, gonado-tropins, and alteration of ovarian source hormones. In this experimental study, animals were divided into four groups, control and CPZ [n=8 per group]. In the treated groups, CPZ was administered by gavage at doses of 3, 10 and 30 mg/kg per day for 28 days. On day 29 the animals were killed after which histopathological and histomorphometric analyses of the ovaries were performed. We evaluated the levels of prolactin serum, luteinizing hormone [LH], follicle-stimulating hormone [FSH], estradiol [E[2] and progesterone. The ovaries of the test groups showed numerous atretic follicles of various sizes. CPZ caused a significant difference between the test groups and the control group [P<0.05] on the amount of atresia and the size of the normal corpora lutea [CL]. The increased dysfunction of the ovaries from the different groups depended on the amount of CPZ administered. The serum concentrations of prolactin and progesterone significantly increased [P=0.05], while the serum concentrations of estradiol, LH and FSH notably decreased [P=0.05], depending on the CPZ dose. CPZ-induced animals had unsuccessful mating and decreased pregnancy rate. The present findings suggest that CPZ-induced disturbances not only depend on prolactin level but the increased prolactin level is largely dose-dependent

Preventive effects of aqueous extract of Berberis integerrima Bge. root on liver injury induced by diabetes mellitus [type 1] in rats

This study was conducted to assessthe preventive effect of aqueous extract of Berberis integerrima Bge. root [AEBIR] on liver damage and oxidative stress induced by diabetes mellitus in rats. Forty male rats were divided into 5 groups as follows: 1- normal [N]; 2- normal + barberry [N+B] [they received barberry root extract for 6 weeks]; 3- diabetic [D] [they received Streptozotocin [STZ], 65 mg/Kg BW /i.p.]; 4- diabetic +barberry before [D+Bb] [they received barberry root extract for 3 weeks before STZ injection and continued for another three weeks]; and 5- diabetic + barberry after [D+Ba] [three days after STZ injection, they received barberry root extract for 3 weeks]. The experimental groups received barberry root extract [500 mg/Kg bw] intra gastric by gavage for 6 weeks. The treatment of diabetic rats with AEBIR showed a significant decreases[p<0.001] in levels of blood glucose, malondialdehyde [MDA], alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP] and total bilirubin while body weight, total protein, superoxide dismutase [SOD], catalase[CAT] and reduced glutathione [GSH] increased [p<0.001] in comparison to diabetic control rats. Consumption of AEBIR in group D+Bb caused significant improvement in all these factors, compared to the group D+Ba. Also in this study, for the first time, we demonstrated that administration of AEBIR before diabetes induction resulted in enhanced amelioration of liver complications compared to the group receiving it after induction, indicating that AEBIR can play a preventive role in such patients

Chlorpromazine-induced hyperprolactinemia on rat's uterus

Hyperprolactinemia is a common side effect of antipsychotic drugs that requires further investigation. The current study was designed to evaluate dose-dependent effect of chlorpromazine [CPZ] on hormonal changes and uterine horn histological structure in rats. Moreover, the mammary glands were analyzed to show hyperprolactinemia-induced histological changes. Albino Wistar rats [n = 32] were divided into four groups. The first group was set as a control. In the three drug-treated groups [eight rats in each group], CPZ was administered by a gavage at doses of 3, 10, and 30 mg/kg/day for 28 days. One day after the last administration of the drug, the animals were sacrificed. Histopathological and histomorphometrical analyses of the uterine horns and mammary glands were carried out to evaluate dose-dependent effect of CPZ on histological structure. Serum levels of prolactin [PRL], estradiol, progesterone, follicle-stimulating hormone [FSH], and luteinizing hormone [LH] were also evaluated. Remarkable [P < 0.05] elevation was observed in CPZ-administrated animals' uterine horn endometrium, myometrium, and perimetrium thicknesses, and the mammary glands were observed with galactorrhea features. The serum level of progesterone and PRL significantly [P < 0.05] increased, while the serum concentration of LH, FSH, and estradiol was notably [P < 0.05] decreased depending on administrated CPZ dose. No histological and biological changes were occurred in the control animals. The present findings suggest that CPZ-induced disturbances not only depend on PRL level and increased PRL level largely depends on administrated doses of the CPZ

Sulpiride-induced hyperprolactinemia in mature female rats: evidence for alterations in the reproductive system, pituitary and ovarian hormones

Background: The prevalence of hyperprolactinemia following administration of conventional antipsychotic drugs requires further investigation. The current study is designed to evaluate the effect of sulpiride [SPD]-induced hyperprolactinemia on alterations to ovarian follicular growth, gonadotropins, and ovarian hormones and to analyze the extent of potential problems in mammary glands

Materials and Methods: A total of 40 albino Wistar rats were divided into four groups: control [no treatment], control-sham [0.3 ml olive oil], low dose SPD [20 mg/kg] and high dose SPD [40 mg/kg]. All compounds were intraperitoneally [IP] administered for a period of 28 days

Results: After 28 days, we dissected the rats' ovarian tissues, uterine horns and mammary glands which were sent for histological analyses. We counted the numbers of normal, atretic follicles and corpora lutea [CL]. Serum levels of prolactin [PRL], estradiol, progesterone, follicle stimulating hormone [FSH] and luteinizing hormone [LH] were evaluated. SPD-administered animals showed sporadic follicular atresia in different sizes associated with higher numbers of CL on the ovaries. The mammary glands exhibited features of galactorrhea. There was remarkable [p<0.05] elevation in SPD-administered animals' uterine horn endometrium, myometrium and perimetrium thicknesses. The serum levels of PRL and progesterone significantly [p<0.05] increased, while the serum concentration of estradiol, LH and FSH notably [p<0.05] decreased according to the SPD administered dose. No histological and biological changes occurred in control-sham animals. SPD-induced animals had unsuccessful attempts at mating and decreased pregnancy rates

Conclusion: The present findings suggest that SPD-induced disturbances depend on PRL level. In addition, an increased PRL level is largely dependent on the administered doses of SPD

Beneficial effects of American ginseng on epididymal sperm analyses in cyclophosphamide treated rats

This study aims to evaluate the protective effects of American ginseng administered by gastric intubation on sperm vital quality in adult male rats treated with cyclophosphamide [CP]. In this experimental study, 28 Adult male Wistar rats were assigned to four groups, seven rats in each. The animals allocated to control, CP treated, Ginseng treated and CP-Ginseng treated groups. Rats were treated with CP [6.1 mg/kg/day, i.p] for 6 weeks. American ginseng was used at a dose of 500 mg/kg/day during treatment. Sperm analysis [motion, count, morphology and viability] were evaluated at the end of the experiments. Sperm motion was assessed by Computer-Assisted Sperm Analysis [CASA]. The data were analyzed using GB stat software. Probability values of p<0.05 and p<0.01 were considered significant. The epididymal sperm counts in the groups that received CP showed significant decreases compared to the control group. Also dead and abnormal sperms significantly increased following CP treatment compared with control. The motility of caudal sperm was reduced significantly with CP treatment. Therefore, according to the results of this study, co-administration of CP and American ginseng can improve these parameters. American ginseng can prevent the cytotoxic effects of CP on sperm quality factors

essential oils compositions of Iranian oregano [Origanum vulgareL.] populations in field and provenance from Piranshahr district, west Azarbaijan province, Iran

Origanum vulgare L. is rarely cultivated in Iran but it is the only species of the Origanum genus growing wild in this country. O.vulgare L. is widely spread all over the country. In this study, parameters of content, composition and antioxidant activity of the essential oils of domestic and wild Iranian Oregano populations were compared with one another. The extractions were performed using a clevenger-type apparatus and the essential oils in the Oregano plants were obtained by hydro-distillation and analyzed by GC/MS. The essential oils were obtained in the Oregano field at yield of [0.80%] and the 4 provenance Oregano [ranging from 0.93% to 1.66% v/w]. In cultivated plant 22 constituents, representing 94.02% and in 4 provenance plants [O.v-w1--- O.v-w4], 21, 25, 22, 20 constituents, representing 96.55%, 95.66%, 95.8%, 94.48% of the oils, respectively, were identified. The two major constituents of the essential oils, carvacrol ranging from 23.54 to 67.09% and, gamma-terpinene ranging from 7.71 to 20.94% were present in relatively equal amounts in all five samples from different localities. Five chemotypes of essential oils were identified. The main chemotype was carvacrol-gamma-terpinene. Furthermore, the antioxidant activity of essential oils of O.vulgare using DPPH radical scavenging was determined. All extracts exhibited almost the same pattern of antioxidant activity as ascorbic acid [vit C]. Our findings demonstrated that the chemical composition of the essential oils of O. vulgare L. varies considering geographical location of collection site, climate and other ecological conditions which suggest both intrinsic/genetic and extrinsic/environmental factors such as: altitude, edaphic, temperature, humidity and climate, may play important roles in determining the oils composition

[Effects of vitamin E and ginseng extract on fertility changes induced by cyclophosphamide in rats]

Cyclophosphamide [CP] is a mustard alkylating agent used in the treatment of some neoplastic diseases such as leukemia, breast and pulmonary cancers. CP administration induces oxidative stress and has cytotoxic effects on normal cells, especially in the reproductive organs. A major side-effect of CP is the alteration of male reproductive function which may result in oligospermia or azoospermia. The aim of the present study was to evaluate the protective effects of vitamin E and ginseng extract on the reproductive system of male rats during cyclophosphamide administration. Fifty-six adult male Wistar rats [220 +/- 30 g] were randomly divided into seven groups of eight. To eliminate the stress induced by gavage, the animals in the first group were considered as the control group and only received water and food. The second group received the placebo for CP via gavage. The third group received CP, 6.1 mg/kg/day, through intraperitoneal administration. The fourth and fifth groups, respectively, received Ginseng, 500 mg/kg/day, and vitamin E 100 mg/kg/day via gavage. The eighth group received both antioxidants by intubation 1 h prior to CP administration for 50 days. The animals were sacrificed one day after the last injection. The testes, body weight, sperm parameters and fertility status of animals were evaluated at the end of the experiments. For the evaluation of fertility index, the male rats were mated with untreated female rats on the 40[th] day of the treatment period. Cyclophosphamide decreased sperm count, lowered fertility rate and decreased testis weight while it increased the number of dead and abnormal sperms [p < 0.01]. In addition, the number of pregnant animals and viable offspring were reduced too; while antioxidant use diminished the adverse effects of CP. The results of the study showed that antioxidative agents vitamin E and Ginseng could diminish the adverse effects of cyclophosphamide in the reproductive system of male rats during cyclophosphamide administration

Effects of melatonin and vitamin E on peripheral neuropathic pain in streptozotocin-induced diabetic rats

Previous studies have indicated that diabetes mellitus might be accompanied by neuropathic pain. Oxidative stress is implicated as a final common pathway in development of diabetic neuropathy. Pharmacological interventions targeted at inhibiting free radical production have shown beneficial effects in diabetic neuropathy. The aim of this study was to investigate and compare the possible analgesic effects of melatonin and vitamin E in diabetic rats. This study was performed on 32 male Wistar rats divided into 4 groups: control, diabetic, melatonin-treated diabetic and vitamin E-treated diabetic. Experimental diabetes was induced by intraperitoneal streptozotocin [50 mg/kg] injection. Melatonin [10 mg/kg, i.p.] and vitamin E [100 mg/kg, i.p.] were injected for 2 weeks after 21 st day of diabetes induction. At the end of administration period, pain-related behavior was assessed using 0.5% formalin test according to two spontaneous flinching and licking responses. The levels of lipid peroxidation as well as glutathione-peroxidase and catalase activities were evaluated in lumbosacral dorsal root ganglia. Formalin-evoked flinching and total time of licking were increased in both acute and chronic phases of pain in diabetic rats as compared to control rats, whereas treatment with melatonin or vitamin E significantly reduced the pain indices. Furthermore, lipid peroxidation levels increased and glutathione-peroxidase and catalase activities decreased in diabetic rats. Both antioxidants reversed the biochemical parameters toward their control values. These results suggest that oxidative stress may contribute to induction of pain in diabetes and further suggest that antioxidants, melatonin and vitamin E, can reduce peripheral neuropathic pain in streptozotocin-induced diabetic rats

[Effects of long term perinatal administration of bupropion on population spike amplitude in neonatal rat hippocampal slices]

The perinatal effects of antidepressants on CNS due to its common usage are important issues in neuroscience research. Bupropion is an atypical antidepressant that is used in smoke cessation under FDA approve widely. The study of synaptic effects of bupropion can reveal its mechanism for nicotine dependence cessation. In this study the long term effects of perinatal bupropion on population spike [PS] amplitudes were investigated. The PS amplitude is a good parameter for synaptic plasticity. Hippocampal slices from 18-25 day old rat's pups were prepared. The exam groups included control and Bupropion treated groups. Bupropion [40 mg/Kg, i.p] was applied in perinatal period daily as pretreatment. Bupropion also was perfused in ACSF [10, 50, 200 micro mol, 30 minutes] and tested for PS amplitude. PS amplitude of Stratum Radiatum was measured before and after Bupropion perfusion. Amplitude of PS before Bupropion perfusion was fitted as 100% for baseline. A concentration of 10 micro M did not reduce PS amplitude and Bupropion had no significant effects on PS amplitude. Bupropion in concentration of 50 micro M could reduce the amplitude of responses in 50% of cases. The 200 micro M of Bupropion perfusion reduced population spike amplitude all slices [n=22]. In the last state population spike amplitude in 8 out of 22 slices completely abolished. Decrease population spike amplitude in non-treated slices with 200 micro M perfusion was more than treated slices. Analyzing of data showed that chronic perinatal exposure to Bupropion in concentrations 50, 200 micro M reduced PS amplitude and we found adaptation synaptic in perfusion 200 micro M compare with Bupropion slices with non-treated

Effects of administration of perinatal bupropion on the population spike amplitude in neonatal rat hippocampal slices

Bupropion is an atypical antidepressant that is widely used in smoke cessation under FDA approval. The study of synaptic effects of bupropion can help to finding out its mechanism[s] for stopping nicotine dependence. In this study the effects of perinatal bupropion on the population spike [PS] amplitude of neonates were investigated. Hippocampal slices were prepared from 18-25 days old rat pups. The experimental groups included control and bupropion-treated. Bupropion [40 mg/Kg, i.p.] was applied daily in perinatal period as pre-treatment. Due to the studying acute effects, bupropion was also added to the perfusion medium [10, 50, 200 micro M for 30 min]. The evoked PS was recorded from pyramidal layer of CA1 area, following stimulation of Schaffer collaterals. A concentration of 10 micro M bupropion had no significant effects on the PS amplitude. The 50 micro M concentration of bupropion reduced the amplitude of responses in 50% of the studied cases. At a concentration of 200 micro M, the recorded PS amplitudes were reduced in all slices [n=22]. Amplitude was completely abolished in 8 out of the 22 slices. The decrease of the PS amplitude was found to be more in the non-pre-treated slices than in the pre-treated slices when both were perfused with 200 micro M bupropion. The results showed the perinatal exposure to bupropion and its acute effects while indicating that at concentrations of 50 and 200 micro M reduced the PS amplitude. It was also found that there was evidence of synaptic adaptation in comparison of bupropion-treated and non-treated slices whereas they were both perfused with 200 micro M

Ureteral calculi in children: What is best as a minimally invasive modality?

Minimally invasive treatment of ureteral calculi in children is a challenging topic. In an evidence-based review, we evaluated the efficacy and safety of extracorporeal shock wave lithotripsy [SWL] and ureteroscopic modalities for this group of patients. In this study, we performed a comprehensive systematic review on articles appeared in the PubMed from 1998 to March 2008. We selected all papers addressing SWL or ureteroscopic management of the ureteral calculi in children and determined the level of evidence of the presenting data. Thirty-nine articles were reviewed and 24 with valid information on SWL or ureteroscopic management of the pediatric ureteral calculi were analyzed. Six articles [25%] were randomized controlled trials and 18 [75%] were retrospective case-controls or case series. The following data were extracted from the 24 articles: in SWL groups, overall success rate was 84.1% [range, 71% to 100%] for the upper ureteral calculi and 76.2% [range, 19% to 91%] for the lower ureteral calculi. Only 61% of the patients had only 1 treatment course, while 8% and 31% of the cases required 2 and more than 2 sessions of treatment, respectively. With ureteroscopic management, the overall success rates were 93.2% [range, 81% to 100%] and 74.4% [range, 20% to 100%] in the lower and upper ureteral calculi, respectively. The main limitations of the series on minimally invasive treatment of pediatric ureteral calculi are lack of powerful randomized controlled trials or prospective data and insufficient patients numbers. Therefore, it is difficult to draw absolute conclusions about successful treatment based on current knowledge