Administration In Wistar Rats Research Articles

Pharmacokinetic Study of Tilianin After Oral Administration in Wistar Rats by HPLC

Pharmacokinetic Study of Tilianin After Oral Administration in Wistar Rats by HPLC

Evaluation of Hematological and Biochemical Effects of Kabuuti Herbal Cough Syrup: A Sub-acute Study in Wistar Rats

Herbal medicines, including Kabuuti cough syrup, have gained popularity in treating various ailments, yet their safety and efficacy require scientific scrutiny. This study aimed to evaluate the hematological and biochemical effects of Kabuuti herbal cough syrup after 28 days of oral administration in Wistar rats. The herbal extracts, containing secondary metabolites like terpenes, alkaloids, steroids, and phenols, were administered at different doses to rats, with distilled water as a control. Hematological and biochemical parameters were assessed, showing no statistically significant changes in most parameters. However, there were decreases in mean corpuscular volume (MCV) levels and lymphocyte percentage and increases in hemoglobin (HB) levels and gamma glutamyl transferase (GGT) levels observed in certain dosage groups. Despite these variations, the overall findings suggest that Kabuuti herbal cough syrup is safe for liver and kidney function in the short term, with no significant adverse effects observed. Keywords: Kabuuti Cough Herbal Preparation; Haematological Effects; Biochemical Effects; Oral Administration; Wistar Rats.

Evaluation of Ovarian Histomorphology and Function Following Clomiphene Citrate and Human Chorionic Gonadotropin Administration in Wistar Rats

Polycystic ovarian syndrome (PCOS), affecting 5-10% of women, is a leading cause of infertility affecting 10-15% of couples globally. Human chorionic gonadotropin (hCG) and clomiphene citrate (CC) are often utilized for the treatment of PCOS. Accordingly, this study explored the effects of CC and hCG on ovarian histomorphology and fertility parameters. Twenty adult female rats were divided into four groups as follows: Group A (control) received only feed and water; Group B received 0.7 mg/kg BW of CC twice daily for five days and was mated before sacrifice on day 19 (before litter); Group C received 0.7 mg/kg BW of CC twice daily for five days, followed by mating and allowed to litter before sacrifice; Group D received 0.7 mg/kg body weight (BW) of hCG on day one, followed by 0.7 mg/kg BW of CC twice daily for five days, and were mated before sacrifice on day 7 (before litter). Results showed that Group B rats had higher, more than other groups, Follicle-stimulating hormone (FSH), Estradiol, Testosterone and Prolactin levels when compared to the control. Similarly, rats in Group B had higher levels of Progesterone while Group D had higher levels of Luteinizing hormone (LH) when compared to the control group. Histological findings demonstrated diverse impacts on ovarian structures, ranging from congested blood vessels to haemorrhages and follicular cysts. Consequently, this study underscores the complexities of drug interactions in reproductive health and provides preliminary insights into the possible adverse effects of CC and hCG on the ovary and fertility parameters.

Effect of Vehicles on the Functional Observational Battery by Oral Gavage Administration in Wistar Rats and Need for Historical Control Data

Effect of Vehicles on the Functional Observational Battery by Oral Gavage Administration in Wistar Rats and Need for Historical Control Data

Impact Of Ikhueniro Dumpsite Leachate On Blood Profile And Blood Film Of Wistar Rats

The challenge of environmental toxicity and the associated unrelenting efforts of man to abate or eradicate its hazards are lifelong efforts. The present study investigated the impact of Ikhueniro dumpsite leachate in Benin City, Nigeria on the hematological blood profile and blood film of Wistar rats. A total of 30 Wistar rats were acclimatized for two weeks and randomly distributed into three groups A to C; group A served as control, while groups B and C were orally administered Leachate only and Leachate + Abatement (Dialium guineenses aqueous leaf extract), respectively, once every 48 hours for 30 days. After the exposure period, the surviving rats in group A and half of the rats in group B and C were examined and sacrificed. The experiment continued with the remaining rats in groups B and C. Group B was given only clean water and C only abatement following ealier stated schedule, after which the surviving rats were sacrificed and samples collected. Hematological analysis showed that leachate administration in Wistar rats caused an increase in white blood cells (27.65%), platelet count (13.35%), and platelet crit (45.45%); with a decrease in red blood cell count (7.52%), hemoglobin (5.40%) and hematocrit (6.12%) of Wistar rats when compared to the control. Geimsa-stained blood film revealed the presence of polymorphs and basophils in the blood film of rats administered dumpsite leachate. Nevertheless, when leachate administration was stopped in the group of rats where it was previously administered, there was a slight improvement in some blood hematological indices. However, the administration of Dialiumguineense leaf extracts better-improved blood hematological indices. The findings of this study indicate that Ikhueniro dumpsite leachate negatively impacted blood hematological indices in Wistar rats. Dumpsite leachate should be handled and treated carefully to avoid potential health hazards in animals.

Assessment of Semi-chronic Toxicity and Lipid-lowering Effect of Jasminum subtriplinerve Blume Oleaceae Extract

Abstract: Jasminum subtriplinerve Blume Oleaceae is a herbal medicine widely used for weight loss and milk gland stimulation. Extract product has been generally used but has not much scientific evidence about its safety and effects. This study aimed to evaluate the semi-chronic toxicity and lipid-lowering effects of Jasminum subtriplinerve Blume leaf extract. The study was performed on Wistar rats and Swiss mice. For semi-chronic toxicity, extracts at doses of 18 mg/kg/day and 54 mg/kg/day showed their safety after 90 days of continuous oral administration in Wistar rats. There was no effect on body weight, hematopoietic parameters, hepatocellular destruction, or liver and kidney function in experimental rats. For the lipid-lowering effect, the extracts at 36 mg/kg/day and 108 mg/kg/day showed a marked decrease in the blood lipid indexes (total cholesterol, triglycerides, non-HDL-C) after 7 days of dosing in Swiss mice on an endogenous dyslipidemic model induced by Poloxamer-407.
 Keywords: Jasminum subtriplinerve Blume Oleaceae, lipid-lowering, dyslipidemia, semi-chronic toxicity.

Design and Evaluation of Pegylated Large 3D Pore Ferrisilicate as a Potential Insulin Protein Therapy to Treat Diabetic Mellitus.

An iron-based SBA-16 mesoporous silica (ferrisilicate) with a large surface area and three-dimensional (3D) pores is explored as a potential insulin delivery vehicle with improved encapsulation and loading efficiency. Fe was incorporated into a framework of ferrisilicate using the isomorphous substitution technique for direct synthesis. Fe3+ species were identified using diffuse reflectance spectroscopy. The large surface area (804 m2/g), cubic pores (3.2 nm) and insulin loading were characterized using XRD, BET surface area, FTIR and TEM analyses. For pH sensitivity, the ferrisilicate was wrapped with polyethylene glycol (MW = 400 Daltons) (PEG). For comparison, Fe (10 wt%) was impregnated on a Korea Advanced Institute of Science and Technology Number 6 (KIT-6) sieve and Mesocellular Silica Foam (MSU-F). Insulin loading was optimized, and its release mechanism was studied using the dialysis membrane technique (MWCO = 14,000 Da) at physiological pH = 7.4, 6.8 and 1.2. The kinetics of the drug's release was studied using different structured/insulin nanoformulations, including Santa Barbara Amorphous materials (SBA-15, SBA-16), MSU-F, ultra-large-pore FDU-12 (ULPFDU-12) and ferrisilicates. A different insulin adsorption times (0.08-1 h), insulin/ferrisilicate ratios (0.125-1.0) and drug release rates at different pH were examined using the Korsmeyer-Peppas model. The rate of drug release and the diffusion mechanisms were obtained based on the release constant (k) and release exponent (n). The cytotoxicity of the nanoformulation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using human foreskin fibroblast (HFF-1) cells. A low cytotoxicity was observed for this nanoformulation starting at the highest concentrations used, namely, 400 and 800 μg. The hypoglycemic activity of insulin/ferrisilicate/PEG on acute administration in Wistar rats was studied using doses of 2, 5 and 10 mg/kg body weight. The developed facile ferrisilicate/PEG nanoformulation showed a high insulin encapsulation and loading capacity with pH-sensitive insulin release for potential delivery through the oral route.

Preclinical study of pharmacokinetic ADME processes of phenosanic acid <i>in vitro</i> and <i>in vivo</i>

BACKGROUND: Phenosanic acid is a synthetic antioxidant, the active ingredient of the original domestic drug recommended for the treatment of epilepsy. To improve the effectiveness and safety of the use of phenosanoic acid, additional study of its pharmacokinetic properties is necessary.
 AIM: To study the pharmacokinetic parameters of the active ingredient of the drug Dibufelon, capsule 200 mg (LLC Piq-Pharma, Russia) in vitro and in vivo systems in rats after single administration in one dose.
 MATERIALS AND METHODS: Phenosanic acid binding to blood plasma proteins, microsomal stability and permeability through the monolayer of Caco-2 cells were evaluated in in vitro tests. The pharmacokinetics parameters were studied after a single intragastric administration in Wistar rats in dose of 80 mg/kg. The samples were analyzed by HPLC-UV.
 RESULTS: A high variability in the degree of binding of phenosanic acid to blood plasma proteins by 2065% depending on the concentration was revealed, relatively high microsomal stability (half-life 1106 789 min, internal clearance 2.05 0.86 l/min/mg protein of liver microsome; residual content after 60 min incubation 87.9 7.8%) and the ability to penetrate through the monolayer of cells Caco-2. The rapid absorbtion of the substance into the systemic bloodstream was established its maximum concentration in blood plasma was observed already 3.6 1.2 hours after administration, and its slow removal from the systemic bloodstream the half-life was about 19 h, the average retention time was about 29 h. Phenosanic acid with different degrees of intensity was distributed to all the examined organs and tissues: kidneys liver brain omentum muscle, and invariably excreted in a small amount with urine and feces, about 0.04% and 5.5%, respectively.
 CONCLUSIONS: As a result of the study, it was found that phenosanic acid is characterized by rapid absorbtion into the systemic bloodstream and a long stay in it invariably, which may be due to the peculiarities of its binding to blood plasma proteins and relatively high metabolic stability, revealed during the corresponding in vitro tests. The study of the permeability and transport of phenosanic acid showed that it can presumably be attributed to compounds with medium permeability and is not a substrate for the transport protein P-glycoprotein (P-gp). The study of tissue availability of phenosanic acid confirmed its entry into peripheral tissues, including the brain, which is the area of implementation of the anticonvulsant effect.

Metabolite Profiling, Stability Testing, Pharmacokinetics, and In Vivo Pattern Recognition Analysis of Arq-e-Keora: A Traditional Unani Formulation.

Arq-e-Keora is a liquid formulation of the Unani system of medicine and used since long for the management of weakness of heart, palpitations, etc. The study was carried out to generate a scientific data for its metabolite profiling, stability testing, pharmacokinetics, and pattern recognition analysis of Arq-e-Keora. Arq-e-Keora has been prepared as water distillate of male wpadix of Pandanus odoratissimus L.f. TLC profiling of Arq-e-Keora was performed using hexane and acetone (7:3, v/v) as a solvent system. The metabolic profiling of volatile compounds was carried out using GC-MS. Pharmacokinetic analysis was performed through GC-MS to evaluate how quickly it absorbs and distributes in plasma. The pattern recognition analysis was performed in order to recognize the pattern and fate of metabolites in rat plasma up to 24 h after single oral administration of Arq-e-Keora. TLC and GC-MS analysis resulted in profiling of 11 and 21 metabolites, respectively. GC-MS analysis revealed that phenethyl alcohol, alpha-terpinolene, beta terpinene, alpha terpinene, beta fenchyl alcohol, hexadecanoic acid, and octadecanoic acid are the major metabolites found in Arq-e-Keora. The stability analysis showed that most of the compounds are stable at refrigerator temperature during their consumption. Pharmacokinetics data of phenethyl alcohol showed its absorption was rapid, with Tmax occurring within 1 h after oral administration of Arq-e-Keora. In vivo pattern recognition analysis suggests that some metabolite expression was altered after its oral administration. As a result, our model could be used for quality, stability, and pharmacokinetic evaluation of various Unani formulations mentioned in Unani Pharmacopoeia of India. This is the first study of pharmacokinetic analysis and metabolite pattern of traditional Unani formulation after its oral administration in Wistar rats.

Jinlian Xiaodu Decoction Protects against Bleomycin-Induced Pulmonary Fibrosis in Rats.

Background Jinlian Xiaodu Decoction (JXD) was reported to have anti-inflammatory and lung protection effects. This study aimed to explore the role and mechanism of JXD on bleomycin (BLM)-induced pulmonary fibrosis (PF). Methods The UHPLC-Q/TOF-MS system was applied to analyze JXD composition. The PF model was established by BLM intratracheal administration in Wistar rats. Subsequently, BLM-treated rats were intragastrically administered with dexamethasone (DXM, 1 g/kg/d) or JXD (3.5, 7 or 14 g/kg/d). Next, the lung coefficient was calculated; H&E, Masson, and TUNEL staining were used for lung morphological analysis and apoptosis assessment. Bronchoalveolar lavage fluid (BALF) biochemical analysis was conducted to count the inflammatory cell number. The expression of inflammatory factors mRNA in the lung tissue and BALF were measured by qRT-PCR. The content and activity of oxidative stress-related proteins were detected. The expression of PF-related, apoptosis-related, and TGF-β1 pathway-related protein were assessed by immunohistochemistry or Western blot. Results Twenty-six compounds were identified from JXD in both negative and positive ion modes. In BLM-induced rats, JXD reduced the lung coefficient and alleviated PF injury. JXD decreased inflammatory cell count and TNF-α, IL-1β, IL-6, and MCP-1 content. Meanwhile, JXD blunted BLM-induced oxidative stress and a high level of HYP. Furthermore, TUNEL analysis found that JXD inhibited cell apoptosis and increased Bcl-2/Bax ratio in BLM-induced lung. Moreover, JXD relieved the role of BLM on α-SMA, TGF-β1, collagen I, fibronectin, E-cadherin protein expression, and the phosphorylation of Smad2/3 in PF rat. Conclusion This study revealed the protective effect and possible element of JXD on BLM-caused PF.

The effect of telmisartan, an angiotensin receptor blocker, on alcohol consumption and alcohol-induced dopamine release in the nucleus accumbens.

Alcohol use disorder remains a major health problem. The mesocorticolimbic dopaminergic system, including the nucleus accumbens region and multiple neural circuits, is involved in its complex underlying mechanism. For instance, alcohol intake stimulates the central and peripheral renin-angiotensin system and increases angiotensin II levels, which predominantly affect angiotensin 1 receptors both in the periphery and in the brain. In this study, we aimed to investigate the effects of the intracerebroventricularly-administered angiotensin 1 receptor blocker telmisartan on the alcohol consumption of male Sardinian alcohol-preferring (sP) rats and on the alcohol-induced dopamine levels in the nucleus accumbens region in Wistar rats. Acute intracerebroventricular administration of telmisartan (100nM) reduced the alcohol intake for 24hours without affecting food and water consumption in sP rats. Acute intracerebroventricular injection of the opioid receptor antagonist naloxone (75nM), tested as a reference compound, also reduced the alcohol consumption in sP rats; however, naloxone's effect lasted only for 30minutes. In microdialysis experiments, telmisartan administered intracerebroventricularly did not change dopamine levels in the nucleus accumbens that had been induced by acute intraperitoneal alcohol administration in Wistar rats. According to these results, further studies are needed to elucidate the role of the renin-angiotensin system on alcohol use disorder pathophysiology.

Box-Behnken Design Optimization of Etoposide Loaded Nanoemulsion: Formulation Development, Cellular Uptake Analysis and Pharmacokinetic Evaluation

Etoposide is widely used in the management of different solid tumors as well as leukemias but low aqueous solubility and poor intestinal permeability limit its oral efficacy. The present investigation aimed to enhance the oral bioavailability of etoposide through formation of nanoemulsion employing Box-Behnken design for formulation optimization. The effect of nanoemulsion composition (concentration of labrasol and solutol HS 15) and process parameters (sonication time) on globule size and polydispersity index were investigated. The optimized formulation was found to be with globule size <200 nm and PDI of 0.129. The zeta potential value −35.8 mV for nanoemulsion indicated the formation of a stable colloidal system. The in-vitro release of etoposide from optimized nanoemulsion was conducted with the help of USP dissolution apparatus type-II in 250 ml of gastric fluid of pH = 1.2 and intestinal fluid of pH 6.8 at 37±0.5 °C using dialysis bag. High drug release was achieved in case of nanoemulsion (47.127±0.82%) as compared to the marketed capsule (25.877±1.33%) and drug suspension (21.374±1.69%) in the simulated intestinal fluid of pH 6.8 after 4 h. The developed delivery system exhibited pH-independent dissolution profile of the loaded etoposide. Confocal laser scanning microscopy (CLSM) study of developed nanoemulsion system was done on intestinal tissue of Wistar rats and optical cross sections revealed deeper penetration of Rhodamine B compared to the dye solution. A comparative in-vivo bioavailability profile of developed formulation, marketed product, and API suspension was also investigated after oral administration in Wistar rats. The relative bioavailability of etoposide loaded nanoemulsion system was 2.5 times higher than the drug suspension and 1.7 times higher than the marketed capsule (Posid®). The findings of the current investigation proved that the developed nanoemulsion system is helpful to improve the bioavailability of P-gp substrate drugs like etoposide that have low oral absorption.

Hepatoprotective Activity of Gentisic Acid on 5-Fluorouracil-induced Hepatotoxicity in Wistar Rats

5-Fluorouracil (5-FU) is a very potent and effective antineoplastic drug that has been widely used for the management of various types of cancer. However, the clinical use of 5-FU is often associated with severe toxicities including hepatotoxicity, which limit its therapeutic use as a potent anticancer agent. The present study aimed to evaluate the hepatoprotective activity of a plant phenolic acid, gentisic acid (GA) (2,5-dihyroxybenzoic acid), against hepatotoxicity induced by 5-FU administration in Wistar rats. The rats were randomly divided into six groups, with six rats per group. Among these, group I and II served as normal control and 5-FU control groups, respectively. The rats in these groups received distilled water (1 mL/kg) for 14 days by oral route. Groups III, IV, V, and VI served as test groups and received GA at doses of 3, 10, 30, and 100 mg/kg body weight, respectively, via oral route for 14 days. From Day 9 onwards, all the groups, except group I, received intraperitoneal dose of 5-FU (20 mg/kg body weight) for five days up to day 14. At the end of the study, the rats were sacrificed, blood was withdrawn for biochemical estimations, and hepatic tissues were excised for histopathological evaluations. Administration of 5-FU at a dose of 20 mg/kg body weight resulted in a significant increase in the serum levels of hepatic biomarkers, including aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, direct bilirubin, and total bilirubin. In comparison to these, 5-FU treatment resulted in a reduction in total protein content (TPC). This was accompanied by significant histopathological changes in the hepatic tissues of the rats, indicating severe hepatotoxicity. Pre- and co-administration of GA with 5-FU at doses of 30 and 100 mg/kg body weight for 14 days resulted in a dose-dependent amelioration of the 5-FU induced alterations in the biochemical and histopathological parameters. The results of the study highlighted the potential of GA as a hepatoprotective agent for the prevention of 5-FU-induced hepatotoxicity.

ZIF-8 nano confined protein-titanocene complex core-shell MOFs for efficient therapy of Neuroblastoma: Optimization, molecular dynamics and toxicity studies

In the present study, we have developed the core-shell metal organic framework (MOF) of zinc, wherein titanocene dichloride (TC) loaded lactoferrin (Lf) functioned as a core. The complexation of TC to Lf was studies using molecular dynamics study, Quantum mechanical model and spectroscopic investigations. Plackett-Burman design was used to screen and select the critical factors affecting the responses (size, zeta potential and PDI) while the effect of those parameter on the quality attributes (size and yield) was studied by means of a Box-Behnken design. The optimised Lf-TC nanoparticles were loaded inside the ZIF-8 framework along with an anticancer agent 5 Fluorouracil and characterized using techniques like FTIR, PXRD, Raman spectroscopy, EDX and UV-NIR spectroscopy and morphological techniques like SEM, TEM, AFM. The compatibility of the loaded ZIF-8 framework was examined by haemocompatibility studies. The potential of developed nanoplatform against Neuroblastoma was assessed using a cell line studies along with in vivo toxicity studies to ascertain its safety for after in-vivo administration in Wistar rats. Therefore, we can conclude that by employing the approach of DOE we were able to optimize the size and yield of Lf-TC NPs and further by loading inside ZIF-8 framework along with an anticancer drug like 5 fluorouracil we were able to develop a potential nanoplatform for the multimodal therapy of Neuroblastoma.

Biodegradable self-assembled nanoparticles of PEG-PLGA amphiphilic diblock copolymer as a promising stealth system for augmented vinpocetine brain delivery.

Vinpocetine (VNP), a semisynthetic drug, is utilized for the treatment of cerebrovascular and memory disorders. This work aimed at formulation of biodegradable VNP long-circulating nanoparticles utilizing Polyethylene glycol methyl ether-block-poly lactide-co-glycolide (PEG-PLGA) copolymer to surmount the drug drawbacks including low oral bioavailability and short elimination half-life. VNP nanoparticles were formulated using nanoprecipitation technique. A 24 factorial design was applied to assess the impact of formulation and process variables on the nanoparticles' characteristics. Statistical analysis revealed that nanoparticles size (Y1) significantly increased with increasing PEG-PLGA amount (X1), poly-vinyl alcohol concentration (X2), and PLGA content (X4), while decreased with increasing sonication time (X3). Furthermore, the entrapment efficiency (Y2) was positively affected by both PEG-PLGA amount and PLGA content, while negatively affected by poly-vinyl alcohol concentration. The optimized formulation prepared using 200mg of PEG-PLGA polymer (PEG: PLGA 2000: 4,500), 0.5% polyvinyl alcohol with sonication time of 60s achieved spherical shape with particle size of 43nm and drug entrapment of 82%. A significant bioavailability enhancement of VNP with marked prolongation of the in vivo systemic exposure of the drug and increased brain levels has also been achieved following intraperitoneal administration in Wistar rats. Thus, the optimized formulation could be regarded as a promising stealth nanocarrier that could surmount the drug pitfalls and enhance its brain delivery.

Application of Nanopharmaceutics for Flibanserin Brain Delivery Augmentation Via the Nasal Route.

Flibanserin (FLB) is a nonhormonal medicine approved by the Food and Drug Administration (FDA) to treat the hypoactive sexual appetite disorder in females. However, the peroral administration of the medicine is greatly affected by its poor bioavailability as a result of its extensive first-pass effect and poor solubility. Aiming at circumventing these drawbacks, this work involves the formulation of optimized FLB transfersome (TRF) loaded intranasal hydrogel. Box–Behnken design was utilized for the improvement of FLB TRFs with decreased size. The FLB-to-phospholipid molar ratio, the edge activator hydrophilic lipophilic balance, and the pH of the hydration medium all exhibited significant effects on the TRF size. The optimized/developed TRFs were unilamellar in shape. Hydroxypropyl methyl cellulose based hydrogel filled with the optimized FLB TRFs exhibited an improved ex vivo permeation when compared with the control FLB-loaded hydrogel. In addition, the optimized TRF-loaded hydrogel exhibited higher bioavailability and enhanced brain delivery relative to the control hydrogel following intranasal administration in Wistar rats. The results foreshadow the possible potential application of the proposed intranasal optimized FLB-TRF-loaded hydrogel to increase the bioavailability and nose-to-brain delivery of the drug.

LC-MS/MS determination of buparlisib, a phosphoinositide 3 kinase inhibitor in rat plasma: Application to a pharmacokinetic study.

Buparlisib is a selective phosphoinositide 3 kinase inhibitor currently evaluated in clinical trials. We developed and validated an LC-MS/MS coupled with a one-step protein precipitation extraction method for the quantitation of buparlisib in rat plasma. After protein precipitation with acetonitrile, the plasma sample was analyzed using a Cortecs UPLC C18 column, with acetonitrile-0.1% formic acid as the mobile phase system. Mass spectrometric detection was conducted in positive ionization mode, with target quantitative ion pair of m/z 411.2 → 367.2 for buparlisib. The calibration curve showed good linearity (1.0-3000 ng/ml), with acceptable accuracy (RE ranging from -6.2 to 5.9%) and precision (RSD within 8.2%) values at quality control concentrations. Extraction recovery from plasma was 80.9-88.7% and the matrix effect was negligible (92.6-95.2%). The validated method presented a simple quantification method of buparlisib in detail and utilized it for a pharmacokinetic study at three dose concentrations after oral administration in Wistar rats.

Simultaneous measurement of perillyl alcohol and its metabolite perillic acid in plasma and lung after inhalational administration in Wistar rats.

The inhalational administration of drugs is a practical and non-invasive approach with the potential to reduce side effects and with a quick onset of therapeutic activity. Perillyl alcohol (POH) is a monoterpene with antitumor activity that currently is undergoing clinical evaluation as an inhalational anticancer agent. A detection method was developed that will be applicable to pharmacokinetic studies of not only POH, but also its longer-lived main metabolite, perillic acid (PA), in lung tissue and plasma after inhalational delivery. The anticancer activity of POH was investigated in vitro with the use of various lung cancer cell lines. Toxicity was established by a standard MTT assay, and apoptosis markers were analyzed by Western blot. For the detection of POH and PA in lungs and plasma, albino Wistar rats were used that were exposed to POH inhalation. Tissues were subjected to chromatographic separation on an Agilent Zorbax Eclipse XDB C18 column, followed by detection of absorption in the ultraviolet (UV) range. In vitro, POH exerted cytotoxic activity against six different lung tumor cell lines, and apoptotic cell death was indicated by induction of active caspase 3 and cleavage of poly (ADP-ribose) polymerase 1 (PARP1). These results demonstrate that inhalational delivery of POH results in effective biodistribution and metabolism of POH in the systemic circulation. In addition, our study introduces a simple, rapid HPLC-UV method with high accuracy for simultaneous detection of POH and its metabolite PA in plasma, and for sensitive detection of PA in lung tissue, which should prove useful for applications in clinical studies.

Histopathological and biochemical correlation of antidiabetic activity of zinc oxide nanoparticles after oral administration in Wistar rats

Nanomaterials have high surface-to-volume ratios and possess unique physiological and biochemical properties modulating a wide range of reactions causing inflammation and cell toxicity. The present...

Histopathological and biochemical correlation of antidiabetic activity of zinc oxide nanoparticles after oral administration in Wistar rats

Nanomaterials have high surface-to-volume ratios and possess unique physiological and biochemical properties modulating a wide range of reactions causing inflammation and cell toxicity. The present work was aimed to evaluate histopathological and biochemical changes in organs of the glucose metabolism after treatment with zinc oxide nanoparticles (ZnONP) in diabetic Wistar rats. Induction of diabetes was done with Streptozotocine and animals were treated with ZnONP in three graded doses in different groups. Glipizide was added in standard treatment and one of the ZnONP groups. Overall histopathological changes were observed as mild to moderate in diabetic animals that received no treatment and minimal in those that received standard treatment as Glipizide. The animals that received ZnONP as a treatment showed minimal to no abnormality detected on histopathology. Biochemical analysis revealed that ZnONP possess antidiabetic and lipid lowering activity which was consistent with histopathology. It is concluded that ZnONP play pivotal role in glucose metabolism and should be investigated further so that they can be introduced into diabetes treatment.