Investigating Preventive Effect of Vitamin D and N-acetylcysteine Against Kidney Injury in Rats Versus the Promotive Effect of Paraquat

Background: Paraquat (PQ) is one of the most important herbicides used in agriculture. Objectives: This study was conducted to compare the preventive effect of vitamin D (Vit D) and N-acetylcysteine (NAC) against kidney injury in rats versus the promotive effect of PQ. Methods: In this study, rats were divided into six groups. The control group (group 1) received normal saline, Vit D group (group 2) received intraperitoneal (IP) injections of+Vit D (2 μg/kg), NAC group (group 3) received NAC (6.25 mg/kg, IP), PQ group (group 4) received PQ (5 mg/kg/d, IP), PQ+Vit D group (group 5) received PQ+Vit D (5 mg/kg/d+2 μg/kg/d, IP) and PQ+NAC group (group 6) received PQ+NAC (5 mg/kg/d+6.25 mg/kg/d, IP). The animals were treated for 7 consecutive days as a sub-chronic exposure. After the collection of urea and serum creatinine, biomarkers of oxidative stress and kidney histopathology were investigated. Results: PQ increased lipid peroxidation (LPO), urea, and serum creatinine, but it significantly decreased total antioxidant capacity (TAC) and thiol groups. In the groups treated with Vit D and NAC, it was observed that LPO, urea, and creatinine significantly decrease compared with the PQ group, and TAC, thiol groups, and Vit D levels increased in kidney tissue. Conclusion: The obtained findings revealed that both Vit D and NAC used as preventive compound were able to reduce oxidative stress and tissue damage caused by PQ toxicity in the kidney

Organic Cation Transporter 3 (OCT3/SLC22A3) and Multidrug and Toxin Extrusion 1 (MATE1/SLC47A1) Protein in the Placenta: Expression, Localization and Function

Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate Mgr. Davoud Ahmadimoghaddam Supervisor Prof. PharmDr. František Štaud, Ph.D. Title of Doctoral Thesis Organic Cation Transporter 3 (OCT3/SLC22A3) and Multidrug and Toxin Extrusion 1 (MATE1/SLC47A1) Protein in the Placenta: Expression, Localization and Function. The aim of the present study was to investigate the expression, localization, and function of organic cation transporter 3 (OCT3, Slc22a3) and multidrug and toxin extrusion protein 1 (MATE1, Slc47a1) in the rat placenta. Using qRT-PCR, Western blotting and immunohistochemical techniques, we demonstrated abundant expression of OCT3 on the basolateral, i.e., fetus-facing side of the placenta, and MATE1 on the apical, i.e., maternal side of the placenta. To investigate the role of these transporters in the transplacental pharmacokinetics, the in situ method of dually perfused rat term placenta was employed in open- and closed-circuit arrangements; 1-methyl-4-phenylpyridinium (MPP+) was used as a model substrate of both OCT3 and MATE1. We provide evidence that OCT3 and MATE1 cause considerable asymmetry between maternal-to-fetal and fetal-to-maternal transport of MPP+ in favor of fetomaternal direction. Using closed- circuit..

Nové přístupy léčby prsního nádoru

Breast cancer is a malignant tumor that originates in the cells of the breast both in women and men. It is the second leading cause of cancer death in women today. Risk factors causing breast cancer in humans comprise, among others, prolonged exposure to estrogen, ionizing radiation, genetic predisposition (BRCA1, BRCA2, others), sedentary lifestyle, high-fat diet, alcohol, and tobacco smoking. Classical treatment strategies include chemotherapy, surgery and radiotherapy. The aim of this diploma thesis was to review recent developments in breast cancer treatment, such as endocrine therapy, molecular targeting therapy as well as breast cancer stem cells

Organic Cation Transporter 3 (OCT3/SLC22A3) and Multidrug and Toxin Extrusion 1 (MATE1/SLC47A1) Protein in the Placenta: Expression, Localization and Function

Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate Mgr. Davoud Ahmadimoghaddam Supervisor Prof. PharmDr. František Štaud, Ph.D. Title of Doctoral Thesis Organic Cation Transporter 3 (OCT3/SLC22A3) and Multidrug and Toxin Extrusion 1 (MATE1/SLC47A1) Protein in the Placenta: Expression, Localization and Function. The aim of the present study was to investigate the expression, localization, and function of organic cation transporter 3 (OCT3, Slc22a3) and multidrug and toxin extrusion protein 1 (MATE1, Slc47a1) in the rat placenta. Using qRT-PCR, Western blotting and immunohistochemical techniques, we demonstrated abundant expression of OCT3 on the basolateral, i.e., fetus-facing side of the placenta, and MATE1 on the apical, i.e., maternal side of the placenta. To investigate the role of these transporters in the transplacental pharmacokinetics, the in situ method of dually perfused rat term placenta was employed in open- and closed-circuit arrangements; 1-methyl-4-phenylpyridinium (MPP+) was used as a model substrate of both OCT3 and MATE1. We provide evidence that OCT3 and MATE1 cause considerable asymmetry between maternal-to-fetal and fetal-to-maternal transport of MPP+ in favor of fetomaternal direction. Using closed- circuit..

Studium exprese, lokalizace a funkční analýzy transportéru organických kationtů 3 (OCT3)

Univerzita Karlova v Praze, Farmaceutická fakulta v Hradci Králové Katedra Pharmacology and Toxicology Kandidát Mgr. Davoud Ahmadimoghaddam Školitel Prof. PharmDr. František Štaud, Ph.D Název disertační práce Organic cation transporter 3 (OCT3) a multidrug and toxin extrusion protein 1 (MATE1) v placentě: exprese, lokalizace a funkce. Cílem této studie bylo popsat expresi, lokalizaci a funkci dvou transportérů, organic cation transporter 3 (OCT3) a multidrug and toxin extrusion protein 1 (MATE1) v placentě potkana. Pomocí qRT-PCR, Western blotting a imunohistochemie jsme detekovali vysokou expresi OCT3 na fetální straně placentárního trofoblastu a expresi MATE1 na straně mateřské. Pro studium role těchto transportérů v transplacentární farmakokinetice jsme využili in situ metodu duálně perfundované potkaní placenty v otevřeném i uzavřeném systému a 1-methyl-4-phenylpyridinium (MPP+) byl použit jako modelový substrát OCT3 a MATE1. Naše výsledky dokazují, že OCT3 a MATE1 způsobují asymetrii v transplacentárním přechodu MPP+ s výraznou převahou transportu z plodu do matky. Pomocí uzavřeného systému duální perfúze potkaní placenty jsme dále popsali schopnost OCT3 a MATE1 transportovat MPP+ z plodu do matky, a to i proti koncentračnímu gradientu. Dále jsme aplikovali různé hodnoty pH (6,5, 7,3, a 8,5)...Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate Mgr. Davoud Ahmadimoghaddam Supervisor Prof. PharmDr. František Štaud, Ph.D. Title of Doctoral Thesis Organic Cation Transporter 3 (OCT3/SLC22A3) and Multidrug and Toxin Extrusion 1 (MATE1/SLC47A1) Protein in the Placenta: Expression, Localization and Function. The aim of the present study was to investigate the expression, localization, and function of organic cation transporter 3 (OCT3, Slc22a3) and multidrug and toxin extrusion protein 1 (MATE1, Slc47a1) in the rat placenta. Using qRT-PCR, Western blotting and immunohistochemical techniques, we demonstrated abundant expression of OCT3 on the basolateral, i.e., fetus-facing side of the placenta, and MATE1 on the apical, i.e., maternal side of the placenta. To investigate the role of these transporters in the transplacental pharmacokinetics, the in situ method of dually perfused rat term placenta was employed in open- and closed-circuit arrangements; 1-methyl-4-phenylpyridinium (MPP+) was used as a model substrate of both OCT3 and MATE1. We provide evidence that OCT3 and MATE1 cause considerable asymmetry between maternal-to-fetal and fetal-to-maternal transport of MPP+ in favor of fetomaternal direction. Using closed- circuit...Katedra farmakologie a toxikologieDepartment of Pharmacology and ToxicologyFaculty of Pharmacy in Hradec KrálovéFarmaceutická fakulta v Hradci Králov

Antinociceptive activity of Cnicus benedictus L. leaf extract: a mechanistic evaluation

Cnicus benedictus, a medicinal herb, traditionally had been used for the treatment of stomachache pain. In this study, the possible efficacy of Cnicus benedictus leaf methanolic extract (CBHE) and also cnicin, one of its major constituents, was measured on pain. Experimental approach: In this study, pain assessment tests include writhing, tail-flick (TF), and formalininduced paw licking test (FIPLT) were used. To understand the possible mediated anti-nociceptive mechanism of CBHE, the opioid mechanism(s), and involvement of the L-arginine/ nitric oxide/cGMP/ATP-sensitive potassium channel pathway (LNCaP) were scrutinized. Findings/Results: In TF and writhing tests, CBHE (150 and 300 mg/kg, i.p) remarkably exhibited an antinociceptive effect compared to that of the control. Furthermore, CBHE (150 and 300 mg/kg, i.p) in comparison with the control showed a noteworthy anti-nociceptive effect (P < 0.01) in the tonic phase of FIPLT. In the writhing test, administration of selective opioid antagonist (naltrindole, nor-binaltorphimine, and naloxonazine) attenuated the anti-nociceptive effect of CBHE (300 mg/kg) in comparison with control. Moreover, pre-treatment with N?-nitro-L-arginine methyl ester hydrochloride, L-arginine hydrochloride, and glibenclamide significantly blocked the CBHE (300 mg/kg) antinociception (P < 0.05) while administration of sodium nitroprusside remarkably potentiated (P < 0.05) the antinociception induced by CBHE in the tonic phase of the FIPLT. Besides, cnicin (30 mg/kg) showed noteworthy anti-nociceptive effects in writhing, TF, and FIPLT paradigms. Conclusion and implications: Taken together, we elucidate that both CBHE and cnicin demonstrated antinociceptive effects in behavioral tests. The possible mechanisms of CBHE antinociception may involve in various neural signaling and modulatory pathways including LNCaP and opioidergic mechanisms

Pentoxifylline Attenuates Arsenic Trioxide-Induced Cardiac Oxidative Damage in Mice

This study was undertaken to evaluate the therapeutic potential effect of pentoxifylline (PTX) against arsenic trioxide (ATO)-induced cardiac oxidative damage in mice. Thirty-six male albino mice were divided into six groups and treated intraperitoneally with normal saline (group 1), ATO (5 mg/kg; group 2), PTX (100 mg/kg; group 3), and different doses of PTX (25, 50, and 100 mg/kg; groups 4, 5, and 6, respectively) with ATO. After four weeks, the blood sample was collected for biochemical experiments. In addition, cardiac tissue was removed for assessment of oxidative stress markers and histopathological changes (such as hemorrhage, necrosis, infiltration of inflammatory cells, and myocardial degeneration). The findings showed that ATO caused a significant raise in serum biochemical markers such as lactate dehydrogenase (LDH), creatine phosphokinase (CPK) and troponin-I (cTnI), glucose, total cholesterol (TC), and triglyceride (TG) levels. In addition to histopathological changes in cardiac tissue, ATO led to the significant increase in cardiac lipid peroxidation (LPO) and nitric oxide (NO); remarkable decrease in the activity of cardiac antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx); and the depletion of the total antioxidant capacity (TAC) and total thiol groups (TTGs). PTX was able to reduce the increased levels of serum cardiac markers (LDH, CPK, cTnI, TC, and TG), cardiac LPO, and improve antioxidant markers (TAC, TTGs, CAT, SOD, and GPx) alongside histopathologic changes. However, no significant changes were observed in elevated serum glucose and cardiac NO levels. In conclusion, the current study showed the potential therapeutic effect of PTX in the prevention of ATO-induced cardiotoxicity via reversing the oxidative stress

Stachys lavandulifolia Causing Estrogen/Progesterone Imbalance during Pregnancy in Wistar Rat: A Time Course Experimental Study: Stachys Lavandulifolia induces abortion in rat

Stachys lavandulifolia is one of the most abortive herbs used in Iran. The present study aimed to investigate the effects of different doses of hydroalcoholic extract of Stachys lavandulifolia (HAESL) on serum estrogen and progesterone levels during different stages (implantation, abortion, and parturition) of pregnancy in Wistar rats. After observing vaginal plaque, the pregnant rats were randomly divided into three studied groups. Each group received the HAESL for three periods including, implantation (days 3 to 5), abortion (days 10 to 12), and parturition (days 19 to 21) of pregnancy. In the abortion and parturition periods, we observed a significant decrease in the estrogen level following administration of HAESL (300 and 900 mg/kg). In addition, we observed a significant decrease in the progesterone level at the highest dose of HAESL in all stages of pregnancy. In conclusion, the present study suggests that Stachys lavandulifolia may affect the estrogen/progesterone levels due to the presence of flavonoid compounds that subsequently lead to abortion, especially during the abortion and parturition periods

Biochemical and Histological Evidence on the Protective Effects of Allium hirtifolium Boiss (Persian Shallot) as an Herbal Supplement in Cadmium-Induced Hepatotoxicity

Background and Objectives. Allium hirtifolium Boiss (Persian shallot), as an edible vegetable, has several pharmacological properties including antimicrobial, anti-inflammatory, and antioxidative effects, while its protective effects in liver cells are controversial. In this study, we examined the effect of A. hirtifolium extract on cadmium- (Cd-) induced hepatotoxicity in rats. Materials and Methods. Thirty-six male Wistar rats were divided into six groups: groups 1, 2, and 3 received vehicle, Cd (100 mg/L/day by drinking water), and A. hirtifolium extract (200 mg/kg/day; orally), respectively. Groups 4, 5, and 6 were Cd groups which were treated with A. hirtifolium extract (50, 100, and 200 mg/kg/day, respectively). After 2 weeks, liver enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) and also oxidative stress biomarkers including lipid peroxidation (LPO), total antioxidant capacity (TAC), total thiol molecule (TTM), and the histopathological changes were determined using standard procedure. Results. The findings showed that Cd caused a remarkable rise in levels of serum hepatic enzymes such as ALT (P<0.001), AST (P<0.01) and ALP (P<0.001) compared with the control group. In addition, Cd led to the decreasing of the levels of TTM (P<0.001) and TAC (P<0.001) and increasing of LPO (P<0.001) in liver tissue in comparison with the control group. In this regard, remarkable vascular congestion, hepatocellular degeneration, and vacuolization were observed in hepatic tissue of Cd-treated rats. Following the administration of A. hirtifolium extract, a significant improvement was observed in the functional and oxidative stress indices of hepatic tissue alongside histopathologic changes. Conclusion. The current study indicated that the A. hirtifolium extract might prevent hepatic oxidative injury by improving oxidant/antioxidant balance in rats exposed to Cd