The time interval between injection of nicotine and tremor initiation: a new index for evaluating nicotine efficacy in rodents.

Tremor is one of the effects of nicotine as a toxic substance, especially in animal models. The intensity and duration of tremors were used to evaluate the effect of nicotine on locomotor activity in laboratory animals. In our observations, the time interval between nicotine injection and the onset of tremor changed depending on the dose. Therefore, by increasing the dose of nicotine in rats, the time interval of tremor onset was also shortened. These results suggest that the time interval between nicotine injection and the onset of tremors can be used as a complementary index for better evaluation of nicotine-derived motor disturbances.

Role of Farnesoid Receptors and Nrf2-mediated Genes in Gentamicin-induced Nephrotoxicity in Rat: A Time-course Study.

INTRODUCTION: Farnesoid-X-activated receptor (FXR) is considered as an upstream controller which could influence the other key regulatory genes encoding cellular antioxidant defense system. METHODS: Thirty-five male Wistar rats (240 ± 20 g) were randomly allocated into five groups: 1) control, 2) received gentamicin (100 mg/kg/d) for three days (GM-3d), 3) seven days (GM-7d), 4) 10 days (GM-10d), and 5) 14 consecutive days (GM-14d). Biochemical measurements of BUN and serum creatinine (SCr), histological assessment of renal samples as well as molecular analysis using real-time qRT-PCR were used to investigate the pattern of changes in different levels. RESULTS: Administration of gentamicin was associated with a significant increase in the BUN and SCr until the 10th day, which then suddenly dropped at the day 14. Meantime, the maximum histological distortion was also seen on the 10th day but in a similar pattern, 14th day was associated with clear improvement. Compared to the control value, the maximum reduction in the mRNA expression of Farnesoid X-activated receptor (FXR), nuclear factor erythroid 2-related factor 2 (Nrf2) and Glutathione cysteine ligase-modulatory subunit (GCLM), occurred at the 3rd and 7th days, respectively. Compared to the control, the mRNA expression of the mentioned genes significantly increased up to day 14. Apart from the 3rd day, the mRNA expression of alpha-glutathione S-transferase (α-GST) and superoxide dismutase (SOD) showed a similar descending and ascending pattern at 7th and 10th days, respectively. CONCLUSION: The expression of FXR, as an upstream controller gene and its downstream pathways mediated by Nrf2, could play a role in gentamicin-induced nephrotoxicity but the pattern of expression was rather biphasic at the acute phase or the subacute ones.  DOI: 10.52547/ijkd.7523.

Potential use of angiotensin receptor blockers in skin pathologies.

Renin-angiotensin system (RAS) components such as angiotensin II, angiotensin receptors (AT1R and AT2R), and angiotensin-converting enzyme (ACE) are expressed in different cell types of the skin. Through AT1R, angiotensin II increases proinflammatory cytokines contributing to fibrosis, angiogenesis, proliferation, and migration of immune cells to the skin. In contrast, AT2R suppresses the effects mentioned above. Many studies show that angiotensin receptor blockers (ARBs) and angiotensin-converting enzymes (ACEi) reduce the proinflammatory cytokines and fibrogenic factors including transforming growth factor ß (TGF-ß), Connective tissue growth factor (CTGF), and IL-6. This review article provides a detailed research study on the implications of ARBs in wound healing, hypertrophic scar, and keloids. We further discuss the therapeutic potentials of ARBs in autoimmune and autoinflammatory skin diseases and cancer, given their anti-fibrotic and anti-inflammatory effects.

Effect of intra-ovarian platelet rich plasma in women with poor ovarian response.

Background: Poor ovarian responder (POR) women, whose ovarian response to gonadotropin stimulation has decreased, are at higher risk of unsuccessful in-vitro fertilization (IVF). Therefore, this study designed to evaluate the effect of intra-ovarian platelet rich plasma (PRP) on POR women. Methods: This single-arm trial research was done on 20 POR women referred to the IVF Unit, university-based hospital, Tehran, Iran between October 2020 and September 2021. For all participants, autologous PRP was injected into each ovary by transvaginal ultrasound guidance under spinal anesthesia between days 12 and 14 of the menstrual cycle. After 12 weeks of PRP injection, embryo transfers were carried out following our routine IVF department protocol. The study outcomes were the number of mature oocytes, and pregnancy rates. Results: The average age of the participants was 41.80±1.82 yr. The average infertility duration was 9.70±1.89 yrs., with 80% primary infertility type. After PRP injection, follicle-stimulating hormone levels dropped about 1% (P=0.499), anti-Mullerian hormone levels were on average 4.5% higher (P=0.356), and estradiol levels raised by 1.2% (P=0.681). The average number of oocytes and their quality increased after PRP injection, while these changes were not significant (p-value>0.05). Chemical pregnancy was detected in 3 (15%) women and clinical pregnancy was detected only in one person. Conclusion: This study revealed that PRP injection into ovaries of POR women is safe and had a tendency to improve ovarian reserve markers and serum levels of AMH, estradiol, number and quality of oocytes.

Cannabidiol interacts with the FXR/Nrf2 pathway and changes the CB1/CB2 receptors ratio in gentamicin-induced kidney injury in rats.

Objectives: Gentamicin-induced nephrotoxicity was used as an experimental model of kidney disease. The present study was performed to assess the therapeutic role of cannabidiol (CBD) against gentamicin-induced renal damage. Materials and Methods: Forty two male Wistar rats were randomly allocated into 6 groups (n=7), including: (1) Control, (2) Vehicle, (3) Gentamicin-treated group (100 mg/kg/day) for 10 days (GM), (4-6) 3 Gentamicin-CBD-treated groups (2.5, 5, and 10 mg/kg/day) for 10 days (GM+CBD2.5, GM+CBD5, GM+CBD10). Serum levels of BUN and Cr, renal histology as well as real-time qRT-PCR were used to investigate the pattern of changes at different levels. Results: Gentamicin increased serum BUN and Cr (P<0.001), down-regulation of FXR (P<0.001), SOD (P<0.05) and up-regulation of CB1 receptor mRNA (P<0.01). Compared to the control group, CBD at 5 decreased (P<0.05) and at 10 mg/kg/day increased the expression of FXR (P<0.05). Nrf2 expression in CBD groups was increased (P<0.001 vs. GM). The expression of TNF-α compared to the control and GM groups, was significantly increased in CBD2.5 (P<0.01) and CBD10 (P<0.05). Compared to the control, CBD at 2.5 (P<0.01), 5 (P<0.001) and 10 (P<0.001) mg/kg/day significantly increased the expression of CB1R. Up-regulation of CB1R in the GM+CBD5, was significantly higher (P<0.05) than the GM group. Compared to the control group, the most significant increase in CB2 receptor expression was observed at CBD10 (P<0.05). Conclusion: CBD particularly at 10 mg/kg/day might be of significant therapeutic benefit against such renal complications. Activating the FXR/Nrf2 pathway and counteracting the deleterious effects of CB1 receptors via CB2 receptors scale-up could be part of the protective mechanisms of CBD.

Silymarin Administration Attenuates Cirrhotic-induced Cardiac Abnormality in the Rats: A Possible Role of ß1-adrenergic Receptors and L-type Voltage-Dependent Calcium Channels.

Background: Cirrhotic cardiomyopathy is a well-recognized cardiac dysfunction in cirrhotic patients. Studies have confirmed the protective effects of silymarin in different types of cardiac injury. This study aimed to examine the effectiveness and molecular mechanism of silymarin against myocardial dysfunction and hypertrophy in a rat model of cirrhosis. Methods: The experiment was performed at Alborz University of Medical Sciences (Karaj, Iran) during 2020-2021. Thirty-two male Wistar rats were randomly divided into four groups of Sham-operated (control group for surgical procedures), Bile Duct Ligated (BDL), and two Silymarin extract (SE)-treated groups of 300 and 600 mg/Kg/day. After 28 days, serum levels of AST, ALT, GGT, and ALP, liver histopathological status, as well as cardiac mechanical function, were assessed. Cardiac ß1-adrenergic receptors (ß1-AR), L-type voltage-dependent calcium channels (L-VDCC), and GATA4 mRNA expression were also determined using real-time RT-PCR. Data analysis was performed using the one-way ANOVA followed by Duncan's multiple range test. Histological data has been analyzed with Kruskal-Wallis nonparametric test. The analysis was performed at P≤0.05. Results: BDL was associated with a significant elevation in serum AST, ALT, GGT, and ALP, development of necrosis and fibrosis of the liver texture, increased Heart Weight and Heart Weight to Body Weight ratio, enhanced cardiac mechanical function as well as a significant up-regulation of ventricular ß1-AR and L-VDCC. Administration of SE600, but not SE300, significantly reduced the serum levels of the enzymes and alleviated signs of liver necrosis and fibrosis. Cirrhotic-induced cardiac dysfunction was also restored by SE600, but not by the lower dose. In addition, cardiac expression of the ß1-AR and L-VDCC was down-regulated toward normal values by either higher or lower doses of the SE. Conclusion: Silymarin treatment in higher dose attenuated cirrhosis-associated cardiac remodeling and reduced cardiac mechanical dysfunctions.

Biliary cirrhosis-induced cardiac abnormality in rats: Interaction between Farnesoid-X-activated receptors and the cardiac uncoupling proteins 2 and 3.

Objectives: This study aimed to evaluate the relationship between Farnesoid-X-activated receptors (FXR) as nuclear regulators of the antioxidant defense system as well as cardiac mitochondrial carrier proteins of UCP2 and UCP3 in cardiac damage induced by cirrhosis. Materials and Methods: Twenty-two male Wistar rats (200-250 g) were randomly divided into 3 experimental groups, including a control group (n=6), a sham-operated group (n=8), and a bile duct ligated (BDL) group (n=8). Four weeks after surgical intervention, biochemical assessment (AST, ALT, GGT, LDH, and ALP), histological observation, and molecular evaluation (FXR, UCP2, UCP3, BNP, Caspase3, and GAPDH) using real-time RT-PCR were performed. Results: Compared with the sham-operation group, the BDL group showed a significant rise in liver enzymes of AST, ALT, GGT, LDH, and ALP. Defined fibrotic and necrotic bundles and thick reticulin fibers were also found in BDL liver tissue. Besides liver morphological alterations, left ventricles of BDL ones were also associated with defined cardiomyocyte hypertrophy, myofiber vacuolization, and clear pigmentation. Findings showed a significant up-regulation of cardiac Brain Natriuretic Peptide (BNP) along with marked down-regulation in hepatic FXR, cardiac FXR, and cardiac UCP2 and UCP3. However, the expression of caspase 3 in the cardiac tissue was not affected by BDL operation during 4 weeks. Conclusion: Expression of FXR as an upstream regulator of cellular redox status, besides the non-enzymatic ROS buffering defense system of cardiac UCPs, has a pivotal role in the pathogenesis of cirrhotic-induced cardiac abnormality in rats.

Effects of platelet-rich plasma on the memory impairment, apoptosis, and hippocampal synaptic plasticity in a rat model of hepatic encephalopathy.

OBJECTIVES: In the present study, we aimed to determine whether intraperitoneal injection of platelet-rich plasma (PRP) could have a neuroprotective effect on learning, memory, and synaptic plasticity impairment as well as hippocampal apoptosis in rats with hepatic encephalopathy induced by bile duct ligated (BDL). METHODS: The rats were divided into four groups: the control, sham, BDL+ V (vehicle), and BDL+ PRP. The BDL rats were treated with PRP immediately after the surgery, and the injection was done every 3 days for 30 days. The passive avoidance and Morris water maze tests were used for the evaluation of learning and memory. The long-term potentiation (LTP), basal-synaptic transmission, and paired-pulse ratio, as an index for measurement of neurotransmitter release probability, were evaluated by field-potential recording. After taking a blood sample for assessment of the liver enzymes, the animals were sacrificed and their hippocampus was removed for evaluation of cleaved caspase-3 by Western blot. RESULTS: Serological assessment of the liver function showed that BDL severely impaired the liver function. Also, PRP treatment could partially improve the liver dysfunction along with recovery in fear memory and spatial learning memory performance, LTP, basal-synaptic transmission, and neurotransmitter release probability. PRP-treated rats also showed a significant reduction in neuronal apoptosis in the CA1 area. CONCLUSIONS: The results of this study suggest that PRP improves cognitive performance and synaptic plasticity in BDL rats via direct neuroprotective property and/or indirectly by improvement of hepatic dysfunction.

Saffron offers hepatoprotection via up-regulation of hepatic farnesoid-X-activated receptors in a rat model of acetaminophen-induced hepatotoxicity.

OBJECTIVES: The most important toxicity of acetaminophen is hepatotoxicity. Farnesoid X-activated receptors (FXR) are one of the nuclear receptor superfamily members which have a pivotal role in the bile acid regulation. The objective of the present study was to examine the role of FXR in mediating the hepatoprotective effects of saffron. METHODS: Male Wister rats were randomly allocated into five groups including a control, vehicle, acetaminophen and two saffron extract groups of 150 and 300 mg/kg/day. The liver function and hepatic FXR expression were evaluated using biochemical assay and real time RT-PCR, respectively. Data analysis was performed using the one-way ANOVA followed by Duncan's multiple range test. RESULTS: Levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) of the acetaminophen group were significantly higher than the control group whereas those of the extract-treated groups were significantly lower than those of the acetaminophen group. The real time RT-PCR findings showed a non-significant down-regulation of FXR mRNA expression, however, a dose-dependent FXR up-regulation was seen in the groups treated with 150 and 300 mg/kg of the extract for 2.67 (p=0.002) and 10.22 (p=0.0001) fold, respectively. CONCLUSION: The main finding of the present study was that the hepatic FXR up-regulation had an important role in saffron hepatoprotective activity.

New mechanistic insights into hepatoprotective activity of milk thistle and chicory quantified extract: The role of hepatic Farnesoid-X activated receptors.

OBJECTIVE: Farnesoid-X-activated receptors (FXR) are key modulators of liver regeneration. Milk thistle and Chicory are known as potent protective remedies in several liver disorders. The objective of this work was to examine the role of FXR in the hepato-healing properties of milk thistle (MTE) and chicory extracts (CE) in a rat model of acetaminophen-induced hepatotoxicity. MATERIALS AND METHODS: Male Wistar rats were randomly divided into seven groups including control, vehicle, acetaminophen (500 mg/kg/day, oral), acetaminophen plus oral MTE 200 and 400 mg/kg/day, and acetaminophen plus oral CE 500 and 1000 /kg/day for 28 days. Liver function and histology as well as the pattern of hepatic FXR expression were assessed after 4 weeks. RESULTS: Administration of acetaminophen was associated with a significant elevation of liver transaminase along with the architectural injuries. In contrast, chronic concomitant administration of both MTE and CE significantly restored the liver function and structural abnormality. The main molecular findings of the study revealed that the lower doses of both MTE and CE led to a marked upregulation of hepatic FXR expression. CONCLUSION: Discovery of the involvement of the nuclear modulating pathways in hepatoprotective activity of the extracts, providesa new mechanistic insight which needs further investigations.

Co-treatment of vitamin D supplementation with enriched environment improves synaptic plasticity and spatial learning and memory in aged rats.

RATIONALE AND OBJECTIVE: Environmental enrichment (EE) has been shown in old rats to improve learning and memory. Vitamin D (VitD) has also been shown to modulate age-related, cognitive dysfunction. As both EE and VitD could work to improve cognition via enhancement of neurotrophic factors, their effects might occlude one another. Therefore, a clinically relevant question is whether noted cognition-promoting effects of EE and VitD can co-occur. METHODS: Aged rats were housed for 6 weeks in one of three housing conditions: environmentally enriched (EE), socially enriched (SE), or standard condition (SC). Further, a 4th group was co-treated with VitD supplementation (400 IU kg-1 daily, 6 weeks) under EE conditions (EE + VitD). RESULTS: Treatment with VitD and EE housing were associated with higher score on measures of learning and memory and exhibited lower anxiety scores compared to EE alone, SE or SC as assayed in the elevated plus maze, Morris water maze, passive avoidance, and open field tasks. Additionally, in the EE + VitD group, mRNA expression levels of NGF, TrkA, BDNF, Nrf2, and IGF-1 were significantly higher compared to expression seen in the EE group. Furthermore, field potential recordings showed that EE + VitD resulted in a greater enhancement of hippocampal LTP and neuronal excitability when compared to EE alone. CONCLUSIONS: These findings demonstrate that in aged rats exposure to EE and VitD results in effects on hippocampal cognitive dysfunction and molecular mechanisms which are greater than effects of EE alone, suggesting potential for synergistic therapeutic effects for management of age-related cognitive decline.

Liposomal and Non-Liposomal Formulations of Vitamin C: Comparison of the Antihypertensive and Vascular Modifying Activity in Renovascular Hypertensive Rats.

BACKGROUND: Liposomes constitute a promising drug delivery vehicle, and are believed to improve drugs' effectiveness. This study was aimed to compare antihypertensive and vascular modifying activities of liposomal and non-liposomal forms of ascorbic acid. METHODS: Forty-nine male Sprague-Dawley rats were randomly divided into seven groups (n=7): A sham vehicle-receiving (Sham-veh), hypertensive (HTN), vehicle-receiving hypertensive (HTN-Veh), two liposomal Ascorbic acid-treated hypertensive at 50 or 100 mg/kg/day (LVC-50 and LVC-100), and two non-liposomal Ascorbic acid-treated hypertensive at 50 or 100 mg/kg/day (VC-50 and VC-100). Systolic blood pressure (SBP) and heart rate (HR) were measured weekly; after 4 weeks, dose-responses to phenylephrine (PE) in the absence and presence of nitro-L-arginine methyl ester (L-NAME), acetylcholine (Ach), and sodium nitroprusside (SNP) were obtained on aortic rings. Data were analyzed with one-way ANOVA and Duncan's multiple range test at a P value of <0.05 using Sigmastat statistical software. RESULTS: Compared to the non-liposomal form, the liposomal one was associated with more prominent effects on the final SBP. Both forms of Ascorbic acid decreased SBP dose-dependently. The basal and stimulated release of Nitric Oxide (NO) was significantly recovered by both forms of Ascorbic acid. The PE maximal responses were not significantly different between the liposomal and non-liposomal groups (P=0.08). Although the Emax of Ach-relaxation response was not different in two preparation forms, Ach-relaxation response induced a lower concentration of the liposomal form of Ascorbic acid (P=0.03. CONCLUSION: The liposomal Ascorbic acid exhibited relaxation activity in significantly lower concentrations. The observed effects were partly mediated by the increased basal release of NO.

Highly Efficient, One Pot, Solvent and Catalyst, Free Synthesis of Novel Quinazoline Derivatives under Ultrasonic Irradiation and Their Vasorelaxant Activity Isolated Thoracic Aorta of Rat.

New quinazoline derivatives were prepared by one pot reaction of anthranilic acid, acetic anhydride and primary amines, under ultrasonic irradiation. As a result, Ultrasonic irradiation has led to affordable, clean synthesis of a variety of target compounds in much higher yields, than traditional methods. This method has numerous advantages: such as higher yields, shorter reactions time, and easier work-up. Several structural classes among these compounds were identified to have vasorelaxant activity. In this respect, all of the newly synthesized quinazolinone derivatives displayed vasorelaxant properties on the isolated thoracic rat aorta. The IC50 of compounds 2a (-6.00 ± 0.55), 2g (-7.31 ± 0.94), 2n (-7.15 ± 0.81) and 2p (-7.77 ± 0.31) was comparable to that seen in the Acetylcholine (-7.13 ± 0.14). The structures of the newly synthesized compounds were confirmed by IR, 1H NMR, 13C NMR, mass spectral studies, elemental analysis, and melting point.

Perinatal outcome in pregnancy with polyhydramnios in comparison with normal pregnancy in department of obstetrics at Shiraz University of Medical Sciences.

OBJECTIVE: Polyhydramnios can lead to maternal and fetal complication during pregnancy, so diagnosis and management can decrease some perinatal complications. STUDY DESIGN: One hundred and fourteen singleton pregnancies were diagnosed with idiopathic polyhydramnios in the department of obstetrics at Shiraz University of Medical Sciences between January 2000 and January 2011 and were compared with 114 normal pregnancies for their perinatal outcome. Variables include birth weight, admission to neonatal intensive care unit (NICU), meconium staining, respiratory distress, fetal death, neonatal death, low 1-min and 5-min APGAR score, primary cesarean section (C/S), preterm delivery (<37 weeks), postpartum bleeding, and placental abruption. RESULTS: Low birth weight (<2500 g), macrosoma (>4000 g), NICU admission, fetal distress, fetal death, lower 1-min and 5-min APGAR score, preterm delivery, and neonatal death were higher in the case group. However, meconium staining and malpresentation were equal between the two groups. Except for prematurity and 1-min and 5-min APGAR scores, there were no significant differences in other maternal or fetal outcomes considering the severity of polyhydramnios. CONCLUSION: Idiopathic polyhydramnios should be considered as a high-risk pregnancy that warrants close surveillance. More studies should be done to detect the best time and interval of fetal surveillance in these patients. Chromosomal and torch studies can determine the definite cause of polyhydramnios.

Chronic endurance exercise antagonizes the cardiac UCP2 and UCP3 protein up-regulation induced by nandrolone decanoate.

BACKGROUND: Several lines of evidence revealed that chronic treatment of anabolic androgenic steroids (AASs) is accompanied with some cardiovascular side effects and in addition they also negatively mask the beneficial effects of exercise training on cardiac performance. METHODS: The present study examined whether the nandrolone decanoate (ND)-induced cardiac effects were mediated by changing the cardiac uncoupling protein 2 (UCP2) and 3 (UCP3) expression. Five groups of male wistar-albino rats including sedentary control (SC), sedentary vehicle (SV), sedentary nandrolone decanoate (SND), exercise control (EC), and exercise nandrolone decanoate (END) were used. ND was injected (10 mg/kg/week, intramuscular) to the animals in the SND and END groups and endurance exercise training was performed on a treadmill five times per week. RESULTS: The protein expressions of cardiac UCP2 and UCP3 have significantly increased in both the SND and EC groups compared to the SC ones. In contrast to UCP3, no significant differences were found between UCP2 protein expressions of the END and SC groups. Compared with the SND group, the exercise training significantly decreased the UCP2 and UCP3 protein expressions in the END group. CONCLUSIONS: The study has indicated that endurance exercise in combination with ND can result in that the exercise effectively antagonizes the effects of ND treatment on UCP2 and UCP3 up-regulation.

Oleuropein improves glucose tolerance and lipid profile in rats with simultaneous renovascular hypertension and type 2 diabetes.

Oleuropein mediates most of the beneficial effects of olive products. This study examined the role of oxidative stress in the effects of oleuropein on lipid profile and blood glucose in rats with simultaneous renovascular hypertension and type 2 diabetes. Eight groups (n = 7-9 each) of male Sprague-Dawley rats including a control, a type 2 diabetic, a renovascular hypertensive, a sham, a simultaneously hypertensive diabetic receiving vehicle, and 3 simultaneously hypertensive-diabetic receiving 20, 40, or 60 mg/kg/day oleuropein were used. Four weeks after treatment, blood glucose, lipid profile, and biomarkers of oxidative stress were measured, and glucose tolerance test (GTT) was performed. Simultaneously hypertensive diabetic rats had significantly higher blood pressure, blood glucose, and serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride and malondialdehyde. They also had lower serum high-density lipoprotein cholesterol, erythrocyte superoxide dismutase, and impaired glucose tolerance. Oleuropein significantly reduced blood pressure, blood glucose, and serum total cholesterol, LDL-C, triglyceride and malondoaldehyde. It also increased serum high-density lipoprotein cholesterol, erythrocyte superoxide dismutase, and improved glucose tolerance. The findings show that the model is associated with impaired glucose tolerance, and adverse lipid profile. They also show that oleuropein, partly by an antioxidant mechanism, improves glucose tolerance and changed lipid profile favorably.

Non-invasive endotracheal delivery of paclitaxel-loaded alginate microparticles.

Aerosolized chemotherapeutics leads to higher, localized and continuous concentrations of active agents in lung tissue with lower side effects for other organs. The present study was performed on jugular vein cannulated rats which endothracheally received 4 mg/kg of free paclitaxel powder (Free-PTX), paclitaxel-loaded alginate microparticles (PTX-ALG-MPs) and i.v. paclitaxel (Anzatax(®)). Pharmacokinetic parameters for Free-PTX and PTX-ALG-MPs contain higher AUC, mean residence time (MRT),half-life and bioavailability, with lower elimination constant (ke). Statistical analysis showed that the amount of paclitaxel per gram of lung tissue after 0.5, 6 and 24 h after administration of Free-PTX was lower than PTX-ALG-MPs. Lung tissue AUC for Free-PTX was lower than PTX-ALG-MPs. According to the obvious advantages obtained, such as dose lowering and increasing paclitaxel residence time and half-life. It should be noted that cell cytotoxicity test on normal airway cell lines was not examined in this study but due to previous reports on safety of inhaled paclitaxel, it can be suggested that pulmonary delivery of paclitaxel can be a useful non-invasive route of administration compared with i.v administration.

Nandrolone decanoate negatively reverses the beneficial effects of exercise on cardiac muscle via sarcolemmal, but not mitochondrial K(ATP) channel.

ATP-sensitive potassium channels are supposed to have a substantial role in improvement of cardiac performance. This study was performed to evaluate whether nandrolone decanoate (ND) and (or) exercise training could affect the expression of cardiac K(ATP) channel subunits. Thirty-five male albino Wistar rats were randomly divided into 5 groups, including sedentary control (SC), sedentary vehicle (SV), sedentary ND (SND), exercise control (EC), and exercise and ND (E+ND). Exercise training was performed on a treadmill 5 times per week. ND was injected (10 mg/kg/week, i.m.) to the rats in the SND and E+ND groups. Following cardiac isolation, the expression of both sarcolemmal and mitochondrial subunits of K(ATP) channel was measured using Western blot method. The expression of sarcolemmal, but not mitochondrial, subunits of K(ATP) channel (Kir6.2 and SUR2) of EC group was significantly higher compared with SC group while ND administration (SND group) did not show any change in their expression. In the E+ND group, ND administration led to decrease of the over-expression of sarcolemmal Kir6.2 and SUR2 which was previously induced by exercise. There was no significant association between the mitochondrial expression of either Kir6.2 or SUR2 proteins and administration of ND or exercise. Supra-physiological dosage of ND negatively reverses the effects of exercise on the cardiac muscle expression of sarcolemmal, but not mitochondrial, K(ATP) channel subunits.