Evaluation of Cilnidipine Loaded Selfmicroemulsifying Drug Delivery System (SMEDDS) by Quantification of Comparative Pharmacokinetic Parameters using validated LC-ESI-MS/MS Bioanalytical Method and Pharmacodynamic Assessment.

OBJECTIVE: Regardless of having desired therapeutic properties many of the recently approved drugs are removed from the developmental pipeline for their clinical use due to low solubility and permeability. Conventional dosage forms are found relatively unsuitable for achieving desired pharmacokinetic and pharmacodynamics profiles.Cilnidipine is 1,4 dihydropyridine derivative calcium channel blocker used for the treatment of hypertension. METHOD: The aim and objective of this study was to develop a precise and significant method in LC-MS/MS for quantification of pharmacokinetic parameters of a cilnidipine loaded self microemulsifying drug delivery system in rat plasma and simultaneously assessed pharmacodynamic characters in comparison with the marketed cilnidipine tablet. Another potential aim of this study is to reduce the dose of the drug in order to counter the dose-dependent toxicities related to chronic use. In the present study, the parent and product ion of cilnidipine was m/z 491.3\237.1. RESULT: The plasma was extracted by protein precipitation technique. The calibration standard concentrations were 1.875, 3.75, 7.50, 15.00, 30.00, 60.00 ng/ml and LLOQ, Low-quality control, Middle-quality control and High-quality control were 1.87, 5.62,22.50,45.00ng/ml respectively. The mobile phase composition was 0.1% formic acid in Milli Q water with 10mM Ammonium acetate as an aqueous solvent and 0.1% formic acid in methanol as an organic solvent. Following oral administration of optimized formulation Cmax (peak plasma concentration) was achieved 21.02±3.17 ng/ml at 0.866 ± 0.11 hr. (Tmax), whereas in the case of marketed tablet Cmax (peak plasma concentration) was achieved 10.16±0.89 ng/ml at 0.93±0.11 hr (Tmax). DISCUSSION: The in-vivo characterizations of the optimized SMEDDS showed significantly better pharmacokinetic parameters in Wistar rats and showed almost 2.4 times enhanced relative bioavailability as compared to the marketed tablet of Cilnidipine which was observed to be correlating to our findings with Non-invasive blood pressure parameter of Wistar rats.

Quantitative Morphological Study of Larynx APUD-Cells in Asphyxial Type of Drowning in Fresh Water (Experimental Study).

An additional microscopic diagnostic sign has been identified for verification of asphyxial type of drowning. In white non-linear male rats (age 2 months) subjected to free drowning, significant hyperplasia of argyrophilic and morphofunctional activity of serotonin-containing APUD-cells of the laryngeal mucosa were revealed under conditions of acute anoxia in comparison with the intact control. These changes promote the development of laryngospasm, which prevents water penetration into the airways and lungs in asphyxial type of drowning. The presence of statistically significant hyperplasia of argyrophilic and morphofunctional activity of serotonin-containing APUD-cells of the laryngeal mucosa under conditions of acute anoxia can be used as an additional diagnostic criterion for asphyxial type of drowning in experimental studies.

Expression of Exploratory Activity of Rat Offspring Depends on the Expression of Exploratory Activity of Their Parents at the Moment of Mating.

The aim of this work was to study the, so far, unexplored possibility that non-genetic inheritance of animal behavioral characteristics could depend on the state of the parents at the time of conception. In this study, we measured the levels of motor and exploratory activity in rats at the ages of 2 and 5 months. Male and female rats were mated at the age of 5 months. The following groups were used: male and female rats with high motor activity at ages of 2 and 5 months (ACT+); male and female rats with high activity at the age of 2 months, but low activity at the age of 5 months (ACT-); male and female rats with low activity at the ages of 2 and 5 months (PAS-); male and female rats with low activity at the age of 2 months, but high activity at the age of 5 months (PAS+). It was found that both males and females ACT+ had significantly higher motor activity, which was observed in the first 10minutes, in the next 20-60minutes, in the center of the cage and more rearings as compared with PAS-rats. Significant differences in the severity of exploratory activity were found between the male offspring of ACT+ and ACT- rats. Differences between the offspring of PAS+ and PAS- rats were observed in both the male and female rats. The motor activity of animals in the period from 20minutes after the start of registration did not differ between groups. Thus, it can be considered that individual characteristics of general motor activity are due to genetically inherited factors, while differences in the level of exploratory activity, apparently, are formed due to non-genetic influences from parents during mating.

Effect of sainfoin (Onobrychis viciifolia Scop.) seed-based diet on rats: A comprehensive evaluation of hemogram, biochemistry, and histopathology.

Sainfoin species (Onobrychis spp.) have been employed for centuries as an essential forage for ruminant animals, both for grazing and as hay. The seeds produced by sainfoin have also been investigated as an animal feed source and were indicated to be a particularly protein-rich supplement for monogastric animals. This study explores the effects of two sainfoin seed inclusion rates in rat diets compared to a control diet, focusing on blood biochemical parameters and a comprehensive histopathological evaluation of multiple organ systems. Thus, we provide a novel contribution to the body of evidence investigating sainfoin seeds as a protein supplement in monogastric animal diets. In this 21-day experiment, seven rats each were assigned to the control group, a 5% sainfoin seed group, and a 10% sainfoin seed group. The control group received standard feed and water; the second group received feed with 5% sainfoin seeds; and the third group received feed with 10% sainfoin seeds. At the experiment's end, necropsies and evaluations were conducted. Histopathological exams revealed normal organ structures in all 21 samples, regardless of the group. Blood analysis showed statistically significant decreases in creatine, ALT, P, Ca, and Mg levels in the sainfoin seed groups compared to the control group, with most values nearing reference levels, suggesting potential benefits. Notably, no adverse effects were observed when sainfoin seeds were included at 5% and 10% in the rat feed. These findings contribute to a growing body of research investigating the inclusion of sainfoin seeds in monogastric animal diets, which is a foundational component of assessing sainfoin's potential as a novel pulse crop for human consumption.

Propolis attenuates diabetes-induced testicular injury by protecting against DNA damage and suppressing cellular stress.

Introduction: Propolis has a wide range of biological and pharmacological actions, including antioxidant properties-particularly its phenolic and flavonoid constituents-that could potentially protect the reproductive system from oxidative damage. Method: Four groups were allocated 40 male Wistar rats each. The vehicle was given to the first group's normal control rats negative control. The second, third, and fourth groups of diabetic rats were given vehicle (diabetic control) and propolis orally at 50 and 100 mg/kg, respectively, for 8 weeks. Diabetes was induced in rats via injection of nicotinamide and streptozotocin (STZ). Fasting blood glucose (FBG) and insulin levels, homeostatic model assessment for insulin resistance (HOMA-IR), and semen analysis were assessed. In addition, assessments of serum reproductive hormones, including total testosterone (TTST), estradiol (E2), follicle-stimulating hormone luteinizing hormone (LH), and prolactin (PRL), were measured at the end of the study. Tissue total testosterone, E2, and dihydrotestosterone were also evaluated. Serum and tissue oxidative enzymes, including catalase (CAT), superoxide dismutase, and glutathione peroxidase activities, were examined, and malondialdehyde content was determined. The pancreatic and testicular tissues were histopathologically examined, and proliferating cell nuclear antigen (PCNA) and B-cell lymphoma 2 (Bcl-2) in testicular tissue were immunohistochemically analyzed. Testicular tissue was examined for DNA integrity using a comet assay. Results: Compared to the STZ-control group, propolis greatly decreased FBG levels and improved the glycemic status of diabetic rats. In comparison to the STZ-DC group, propolis increased the number of sperm cells and the percent of morphologically normal and viable sperm in male rats, improving their fertility. Propolis also restored the pancreatic islets, protected the testis from oxidative stress, and increased levels of reproductive hormones in the blood, especially testosterone. Moreover, propolis at high doses demonstrated a strong positive response for Bcl-2 and a negative expression of proliferating cell nuclear antigen in spermatogenic cells. Conclusion: The data obtained strongly indicate that STZ causes severe impairments to the testis whereas propolis, acting as an antioxidant, protects against the adverse effects of STZ on the testis.

Bio distribution and acute toxicity profiling of Pluronic F127 coated Titanium dioxide nanotubes in adult Wistar rats.

Metal and metal oxide nanoparticles are gaining immense attention among researchers owing to their admirable application potentials in various therapeutic events. Titanium dioxide (TiO2) has been recognized as one of the leading candidates in this category and holds wide interest within the scientific community. Among the various morphological nanoforms of TiO2, nanotube is grabbing remarkable attention as they have succeeded as an active vehicle in various medical procedures like intravascular stenting, drug delivery, as biosensors etc. This ultimately demands toxicity profiling of nanotubes in various aspects. Present study elaborates a concept through which acute toxicity profiling of TiO2 nanotubes in adult Wistar rats is presented. TNTs were synthesized via solvo-thermal approach and surface coated with a biocompatible polymer; Pluronic-F127 (P-F127). This step assists in ameliorating the troubles associated with the nanomaterial dispersion stability. The experimental rats were intraperitoneally administered with TNT-P (10 mg/kg) and sacrificed on different time periods (3rd, 7th and 14th days). Biodistribution of the material was tracked in major tissues including brain, liver, spleen and kidneys. A set of acute toxicity studies was performed which comprises hematology evaluation, biochemical studies, antioxidant detection, analysis of urine parameters, immune modulation study and histopathology evaluation. Many of the experiments revealed an unaltered physiological response in rats; except for some biochemical and hematology parameters. Overall study suggests that, TNT-P do not result into a negative response in Wistar rats over 14 days.

Genetic diversity of the largest African mole-rat genus, Bathyergus. one, two or four species?

Recent advances in sequencing technology and phylogenetic methods allow us to solve puzzling taxonomic questions using detailed analyses of genetic diversity of populations and gene flow between them. The genus of solitary-living dune mole-rat, Bathyergus, is quite unique among six genera of African mole-rats. The animals are by far the largest and the only scratch digging mole-rat genus possessing a skull less adapted to digging, grooved upper incisors, and more surface locomotor activity. Most authors recognize two species of dune mole-rats, B. suillus and B. janetta, but according to others, the genus is monotypic. In addition, recent molecular studies have revealed cryptic genetic diversity and suggested the existence of up to four species. In our study, we used mitochondrial and genome-wide nuclear data collected throughout the distribution of the genus to investigate the number of species. In agreement with previous studies, we found Bathyergus to be differentiated into several distinct lineages, but we also found evidence for a degree of gene flow between some of them. Furthermore, we confirmed that B. janetta is nested within B. suillus, making the latter paraphyletic and we documented an instance of local mitochondrial introgression between these two nominal species. Phylogeographic structure of the genus was found to be very shallow. Although traditionally dated to the Miocene, we found the first split within the genus to be much younger estimated to 0.82 Ma before present. Genealogical distinctiveness of some lineages was very low, and the coancestry matrix showed extensive sharing of closely related haplotypes throughout the genus. Accordingly, Infomap clustering on the matrix showed all populations to form a single cluster. Overall, our study tends to support the existence of only one species of Bathyergus namely, B. suillus. Environmental niche modelling confirmed its dependence on sandy soils and the preference for soils with relatively high carbon content. Bayesian skyline plots indicate recent population decline in the janetta lineage, probably related to global environmental change.

The modulatory role of serotonin-1A receptors of the basolateral amygdala and dorsal periaqueductal gray on the impact of hormonal variation on the conditioned fear response.

Despite significant advances in the study of fear and fear memory formation, little is known about fear learning and expression in females. This omission has been proven surprising, as normal and pathological behaviors are highly influenced by ovarian hormones, particularly estradiol and progesterone. In the current study, we investigated the joint influence of serotonin (5-HT) neurotransmission and estrous cycle phases (low or high levels of estradiol and progesterone) on the expression of conditioned fear in a group of female rats that were previously divided according to their response to stressful stimuli into low or high anxiety-like subjects. The baseline amplitude of the unconditioned acoustic startle responses was high in high-anxiety female rats, with no effect on the estrous cycle observed. Data collected during the proestrus-estrus phase revealed that low-anxiety rats had startle amplitudes similar to those of high-anxiety rats. It is supposed that high-anxiety female rats benefit from increased estradiol and progesterone levels to achieve comparable potentiated startle amplitudes. In contrast, female rats experienced a significant decrease in hormone levels during the Diestrus phase. This decrease is believed to play a role in preventing them from displaying a heightened startle response when faced with strongly aversive stimuli. Data collected after 5-HT and 8-OH-DPAT were administered into the basolateral nuclei and dorsal periaqueductal gray suggest that 5-HT neurotransmission works with progesterone and estrogen to reduce startle potentiation, most likely by activating the serotonin-1A receptor subtype.

UHPLC-MS/MS profiling and in vivo aphrodisiac and androgenic effects of the aqueous extract of the roots of Schumanniophyton magnificum (K. Schum.) Harms.

ETHNOPHARMACOLOGICAL RELEVANCE: Schumanniophyton magnificum is a medicinal plant used to manage many ailments including malaria, skin diseases, parasitic infections, male sexual dysfunctions, female infertility and typhoid fever. However, no scientific investigation has been made for its folkloric use by the "Baka" Pygmies of Cameroon as an aphrodisiac. AIM OF THE STUDY: To investigate the aphrodisiac and androgenic activities of the aqueous extract of the roots of Schumanniophyton magnificum in male rats and analyze the phytoconstituents by UHPLC/MS. MATERIALS AND METHODS: Twenty-five male rats of 16-weeks old were divided into 5 groups and orally treated for 30 days with distilled water (10 ml/kg), or sildenafil citrate (5 mg/kg), or the aqueous extract of Schumanniophyton magnificum (43 mg/kg, 86 mg/kg and 172 mg/kg). The sexual behaviour parameters were monitored on day 1 and 30 by pairing male rats to receptive females. At the end of the experiment, rats were killed and the blood and reproductive organs were collected for histological sectioning, sperm analysis and biochemical analysis. The presence of phytoconstituents and their structures were revealed by UHPLC/MS. RESULTS: The plant extract significantly increased the mount, ejaculation and intromission frequencies in comparison to those in the normal control group; and significantly doubled the serum testosterone levels (2.15 ± 0.70 ng/ml) compared to the normal control group. UHPLC/MS of the aqueous extract of Schumanniophyton magnificum identified 7 major compounds such as Schumanniofioside A, Noreugenin and Rohitukine, with antioxidant and antibacterial activities. The plant extracts significantly increased the penile nitric oxide levels (P <0.05). These results were similar to those obtained after administration of sildenafil citrate. CONCLUSIONS: The aqueous extract of Schumanniophyton magnificum could be an alternative for erectile dysfunction management.

Bone marrow-derived mesenchymal stem cells reduce CCl4-induced kidney injury and fibrosis in male Wistar rats.

AIM: This study explores the possible therapeutic role of rats and mice bone marrow-derived mesenchymal stem cells (BM-MSCs) on renal damage and toxicity brought on by carbon tetrachloride (CCl4) in Wistar rats. METHODS: Following an intraperitoneal injection of CCl4 (0.5 mL/kg b.w. twice weekly) for eight weeks, male Wistar rats were intravenously treated with rats and mice BM-MSCs (1 × 106 cells in 0.2 mL Dulbecco's Modified Eagle Medium (DMEM)/rat/week) a week for four weeks. Kidney functions were evaluated and kidney samples were examined using hematoxylin and eosin (H&E), Masson's trichrome (MT) staining techniques, and electron microscopy analysis. Kidney cyclooxygenase-2 (COX-2), protein 53 (p53), and tumor necrosis factor-α (TNF-α) were detected by immunohistochemical staining techniques. Additionally, bioindicators of oxidative stress and antioxidant defense systems were identified in kidney tissue. RESULTS: In CCl4-injected rats, serum creatinine, urea, and uric acid levels significantly increased, as did renal lipid peroxidation (LPO), while superoxide dismutase, glutathione peroxidase (GPx), glutathione (GSH) transferase, and GSH levels significantly dropped in the kidneys. Histologically, the kidneys displayed a wide range of structural abnormalities, such as glomerular shrinkage, tubular dilations, inflammatory leukocytic infiltration, fibroblast proliferation, and elevated collagen content. Inflammatory cytokines like COX-2 and TNF-α as well as the pro-apoptotic mediator p53 were considerably upregulated. Treatment of BM-MSCs from mice and rats with CCl4-injected rats considerably reduced the previously noted abnormalities. CONCLUSIONS: By boosting antioxidant defense and reducing apoptosis and inflammation, BM-MSCs from mice and rats were able to enhance kidney function and histological integrity in rats that had received CCl4 injections.

Repeated dose, 28-day oral toxicity study of curcumin, anthocyanins, and sodium nitrite in Wistar rats.

OBJECTIVE: The goal of the present study was to examine the repeated dose 28-day oral toxicity of curcumin, anthocyanins, and sodium nitrite in Wistar rats. METHODS: For this purpose, forty-eight male Wistar rats were randomly divided into 8 groups (n = 6 each), encompassing untreated controls and experimental groups treated with curcumin, anthocyanins, and sodium nitrite. Three rats from each group were sacrificed by cervical dislocation under di-ethyl ether anesthesia after 2 and 4 weeks of therapy, respectively. Blood samples were collected for serum chemistry. All of the animals' livers, hearts, and kidneys were removed and sent for histopathological examination. RESULTS: After two weeks of inquiry, certain groups displayed higher hematological values, while others had lower values compared to the control group. AST, CK, and LDH enzyme activity were higher in groups 2-8, but urea concentrations were higher in groups 6 and 8. After four weeks, the Hb, MCH, and MCHC values in group 4 were greater, as were the WBC levels in groups 4 and 6, whereas other groups had lower MCV and WBC values. The weekly body weight gain was insignificantly different between treatment groups. Throughout the experiment, none of the animals perished. Male rats' liver, kidney, and heart underwent histopathological changes after ingesting curcumin, sodium nitrite, and anthocyanin. CONCLUSION: Based on the findings, rats were more detrimental when curcumin, sodium nitrite, and anthocyanin were ingested together than when they were consumed individually, as evidenced by histopathological abnormalities in the liver, kidneys, and heart.

Are Hyperglycemia-Induced Changes in the Retina Associated with Diabetes-Correlated Changes in the Brain? A Review from Zebrafish and Rodent Type 2 Diabetes Models.

Diabetes is prevalent worldwide, with >90% of the cases identified as Type 2 diabetes. High blood sugar (hyperglycemia) is the hallmark symptom of diabetes, with prolonged and uncontrolled levels contributing to subsequent complications. Animal models have been used to study these complications, which include retinopathy, nephropathy, and peripheral neuropathy. More recent studies have focused on cognitive behaviors due to the increased risk of dementia/cognitive deficits that are reported to occur in older Type 2 diabetic patients. In this review, we collate the data reported from specific animal models (i.e., mouse, rat, zebrafish) that have been examined for changes in both retina/vision (retinopathy) and brain/cognition, including db/db mice, Goto-Kakizaki rats, Zucker Diabetic Fatty rats, high-fat diet-fed rodents and zebrafish, and hyperglycemic zebrafish induced by glucose immersion. These models were selected because rodents are widely recognized as established models for studying diabetic complications, while zebrafish represent a newer model in this field. Our goal is to (1) summarize the published findings relevant to these models, (2) identify similarities in cellular mechanisms underlying the disease progression that occur in both tissues, and (3) address the hypothesis that hyperglycemic-induced changes in retina precede or predict later complications in brain.

Tropine exacerbates the ventilatory depressant actions of fentanyl in freely-moving rats.

Our lab is investigating the efficacy profiles of tropine analogs against opioid-induced respiratory depression. The companion manuscript reports that the cell-permeant tropeine, tropine ester (Ibutropin), produces a rapid and sustained reversal of the deleterious actions of fentanyl on breathing, alveolar-arterial (A-a) gradient (i.e., index of alveolar gas exchange), and arterial blood-gas (ABG) chemistry in freely-moving male Sprague Dawley rats, while not compromising fentanyl analgesia. We report here that in contrast to Ibutropin, the injection of the parent molecule, tropine (200 µmol/kg, IV), worsens the adverse actions of fentanyl (75 µg/kg, IV) on ventilatory parameters (e.g., frequency of breathing, tidal volume, minute ventilation, peak inspiratory and expiratory flows, and inspiratory and expiratory drives), A-a gradient, ABG chemistry (e.g., pH, pCO2, pO2, and sO2), and sedation (i.e., the righting reflex), while not affecting fentanyl antinociception (i.e., the tail-flick latency) in freely-moving male Sprague Dawley rats. These data suggest that tropine augments opioid receptor-induced signaling events that mediate the actions of fentanyl on breathing and alveolar gas exchange. The opposite effects of Ibutropin and tropine may result from the ability of Ibutropin to readily enter peripheral and central cells. Of direct relevance is that tropine, resulting from the hydrolysis of Ibutropin, would combat the Ibutropin-induced reversal of the adverse effects of fentanyl. Because numerous drug classes, such as cocaine, atropine, and neuromuscular blocking drugs contain a tropine moiety, it is possible that their hydrolysis to tropine has unexpected/unintended consequences. Indeed, others have found that tropine exerts the same behavioral profile as cocaine upon central administration. Together, these data add valuable information about the pharmacological properties of tropine.

Differential absorption and metabolic characteristics of organic acid components in pudilan xiaoyan oral liquid between young rats and adult rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Pudilan Xiaoyan Oral Liquid (PDL) is a proprietary Chinese medicinal preparation approved by the State for treating acute pharyngitis in both adults and children (Approval No. Z20030095). It is worth noting that children exhibit unique physiopathological characteristics compared to adults. However, the in vivo regulatory characteristics of PDL in treating acute pharyngitis in children remain incompletely understood. AIM OF THE STUDY: The differential absorption and metabolism characteristics of the main pharmacological components in PDL in young and adult rats were investigated with a view to providing a reference for preclinical data of PDL in medication for children. MATERIALS AND METHODS: This study utilized UPLC-Q-TOF-MS to investigate the pharmacodynamic material basis of PDL. The focus was on the gastrointestinal digestion and absorption characteristics of organic acid components in PDL (PDL-OAC), known as the primary pharmacodynamic components in this formulation. The research combined in vitro dynamic simulation and a Quadruple single-pass intestinal perfusion model to examine these characteristics. The permeability properties of PDL-OAC were evaluated using an artificial parallel membrane model. Additionally, an acute pharyngitis model was established to evaluate the histopathological condition of the pharynx in young rats using H&E staining. The levels of IL-1ß, TNF-α, IL-6, and IL-10 in blood and pharyngeal tissue homogenates of young rats were quantified using ELISA kits. RESULTS: A total of 91 components were identified in PDL, including 33 organic acids, 24 flavonoids, 14 alkaloids, 5 terpenoids and coumarins, 3 sugars, and 12 amino acids. The PDL-OAC exhibited a significant reduction in IL-1ß, TNF-α, IL-6, and IL-10 levels in the pharyngeal tissues of young rats with acute pharyngitis. Results from dynamic simulation studies of gastrointestinal fluids revealed that the PDL-OAC (Specifically chlorogenic acid (CGA), gallic acid (GA), chicoric acid (CRA), and caffeic acid (CA)) were effectively stabilized in the gastrointestinal fluids of both children and adults in vitro. Young rats, characterized by thinner intestinal walls and higher permeability, efficiently absorbed the four organic acids across the entire intestinal segment. The absorption of CGA, GA, and CRA followed a concentration-dependent pattern, with CGA and GA absorption being influenced by exocytosis. CONCLUSION: The efficacy of the PDL-OAC in treating acute pharyngitis was demonstrated in young rats. The absorption rate of these components was observed to be faster in young rats compared to adult rats, underscoring the need for dedicated studies on the drug's usage in children. This research provides valuable insights for the appropriate clinical use of PDL in pediatric patients.

Noninvasive microvascular imaging in newborn rats using high-frequency ultrafast ultrasound.

Ultrasound imaging stands as the predominant modality for neonatal health assessment, with recent advancements in ultrafast Doppler (µDoppler) technology offering significant promise in fields such as neonatal brain imaging. Combining µDoppler with high-frequency ultrasound (HF-µDoppler) presents a potential efficient avenue to enhance in vivo microvascular imaging in small animals, notably newborn rats, a crucial preclinical animal model for neonatal disease and development research. It is necessary to verify the imaging performance of HF-µDoppler in preclinical trials. This study investigates the microvascular imaging capabilities of HF-µDoppler using a 30 MHz high-frequency linear array probe in newborn rats. Results demonstrate the clarity of cerebral microvascular imaging in rats aged 1 to 7 postnatal days, extending to whole-body microvascular imaging, encompassing the central nervous system, including the brain and spinal cord. In conclusion, HF-µDoppler technology emerges as a reliable imaging tool, offering a new perspective for preclinical investigations into neonatal diseases and development.

Tactile stimulation of young WAG/Rij rats prevents development of depression but not absence epilepsy.

Investigations in Wistar Albino Glaxo from Rijswijk (WAG/Rij) rats that are susceptible to genetic absence epilepsy have demonstrated that environmental modifications affect absence seizures. Previously, we showed that neonatal tactile stimulations produce disease-modifying effect on genetically determined absence epilepsy and associated depression in Wag/Rij rats. The study presented here examined the effect of TS during late ontogenesis (adolescence and young adulthood) on epilepsy and depression outcomes in this genetically epileptic rat strain. On postnatal day (PND) 38, male WAG/Rij rats randomly were assigned to either the tactile stimulation (TS), handled or control group (unhandled) with 8 animals in each group. Following a 7-day adaptation period to their new surroundings, the animals were submitted to tactile stimulation from PND 45 to PND 90, five days per week, for 5 min daily. The tactile-stimulated rat was removed from its cage, placed on the experimenter's lap, and had its neck and back gently stroked by the researcher. The handled rats were taken to another cage and left alone for 5 min daily from PND 45 to PND 90. The control rats were left undisturbed in their home cage, except for regular cage cleaning. After PND 90, all rats were left undisturbed until behavioral testing and EEG recording. When the animals were 7 months old, they were subjected to the sucrose consumption test (SCT) and the forced swimming test (FST). Electroencephalogram (EEG) recordings were made at 8 months of age in order to measure electroencephalographic seizure activity, thus, the spike-wave discharges (SWDs). Tactile-stimulated rats showed increased sucrose consumption and number of approaches to the sucrose solution in the SCT when compared with the handled and control rats. In the FST, rats in TS group showed lower immobility time and greater immobility latency, active swimming time and diving frequency than the handled and control rats. The duration and the number of seizures were not different amongst the groups. The data obtained suggest that TS in young rats is able to prevent depression in WAG/Rij rats.

Evaluation of the Potential Protectivity of Both Allium sativum and Zingiber officinale on the Cadmium-Induced Testicular Damage in Rats.

Background: Cadmium (Cd) is a widely spread environmental pollutant, listed among the unsafe metals due to known toxic effects on multiple organs, including the testes. In this study, we aim to evaluate the potential protectivity of garlic and ginger extracts on Cd-induced damage of the testis in rats. Materials and Methods: Fifty-six adult male albino rats were alienated into seven groups; control group, garlic-treated group, and ginger-treated group were given garlic and ginger extracts at doses of 250 mg and 120 mg/kg b.wt/day, Cd-treated group received 8.8 mg/Kg b.wt/day of Cd chloride, and the protected groups were given Cd and co-treated with garlic, ginger, or both extracts. The testes were subjected to different procedures to assess the oxidative status and histopathological changes. Results: Cd-treated rats showed a significant reduction in the testis weight and morphometric measurements of the seminiferous tubules compared to the control group. Cd administration resulted in a marked drop in the testosterone level and activities of antioxidative enzymes. Moreover, Cd induced histopathological changes in the seminiferous tubules. Co-administration of garlic and ginger extracts with the Cd showed partial improvement in the investigated parameters toward the control figures and improvement in the morphological changes. Co-treating both extracts together and the Cd resulted in complete normalization of these adverse effects of Cd. Conclusion: These findings indicated that garlic and ginger extracts could ameliorate the harmful effects of Cd on the testis. This effect was more prominent when garlic and ginger extracts were co-administered together with Cd.

Sub-chronic toxicity of the active fraction of a modified Huang-Lian-Jie-Du Decoction.

A traditional Chinese herbal medicine formula named Huang-Lian-Jie-Du Decoction (HLJDD) has been used to cure various inflammatory diseases with a long history. However, one component of HLJDD Gardeniae fructus has remarkable liver and kidney toxicities. Therefore, it was altered with Dictamni cortex to form a modified HLJDD (MHLJDD). In this study, we aimed to evaluate the sub-chronic toxicity of the active fraction of MHLJDD (MHLJDD-F) in rats. Adult rats of both sexes were intragastrically administered with vehicle or MHLJDD-F (at the dose of 170, 340, and 680 mg/kg/day) once daily for 90 days. Half of the rats from each group were kept for an additional 30-day period to observe the drug withdrawal effect. The signs of toxicity and mortality of the rats were observed, and the body weight and food consumption were recorded. Blood was collected for hematological and biochemical analyses and major organs were weighed and harvested for histopathological examinations. The results revealed that no systemic toxicity of MHLJDD-F was found during the experiments. Organ coefficients and pathological alterations of major organs were comparable to the control rats. The no-observed adverse effect level (NOAEL) of MHLJDD-F was found up to 680 mg/kg/day. All these results demonstrated that long-term oral administration of MHLJDD-F did not cause significant toxicity, which is worthy to be widely applied as a new herbal medicine in pre-clinical and clinical studies.

Therapeutic potential of silver nanoparticles from Helianthemum lippii extract for mitigating cadmium-induced hepatotoxicity: liver function parameters, oxidative stress, and histopathology in wistar rats.

Introduction: This study explores the therapeutic potential of silver nanoparticles (Ag NPs) synthesized using a Helianthemum lippii extract in mitigating cadmium-induced hepatotoxicity in Wistar rats. Given the increasing environmental and health concerns associated with cadmium exposure, novel and eco-friendly therapeutic strategies are essential. Methods: Ag NPs were characterized using X-ray diffraction, UV-Vis spectrometry, and energy-dispersive X-ray spectroscopy with scanning electron microscopy, confirming their formation with a cubic crystal structure and particle sizes ranging from 4.81 to 12.84 nm. A sub-acute toxicity study of Ag NPs (2 mg/kg and 10 mg/kg) was conducted, showing no significant difference compared to untreated control rats (n = 3 animals/group). Subsequently, adult Wistar rats (n = 5/group) were divided into a control group and three experimental groups: Ag NPs alone, exposure to 50 mg/kg CdCl2 in drinking water for 35 days, and CdCl2 exposure followed by 0.1 mg/kg/day Ag NPs intraperitoneally for 15 days. Results: In the CdCl2-exposed group, there was a significant decrease in body weight and increases in alanine and aspartate transaminase levels (p < 0.05 vs. control), indicating hepatotoxicity. Additionally, antioxidant defenses were decreased, and malondialdehyde levels were elevated. Liver histology revealed portal fibrosis, inflammation, necrosis, sinusoid and hepatic vein dilation, and cytoplasmic vacuolations. Treatment with Ag NPs post-CdCl2 exposure mitigated several adverse effects on liver function and architecture and improved body weight. Discussion: This study demonstrates the efficacy of Ag NPs synthesized via a green method in reducing cadmium-induced liver damage. These findings support the potential of Ag NPs in therapeutic applications and highlight the importance of sustainable and eco-friendly nanoparticle synthesis methods. By addressing both toxicity concerns and therapeutic efficacy, this research aligns with the growing emphasis on environmentally conscious practices in scientific research and healthcare.

Iron administered in the neonatal period changed memory, brain monoamine levels, and BDNF mRNA expression in adult Sprague-Dawley rats.

BACKGROUND: Iron is one of the key microelements in the mammalian body and is the most abundant metal in the brain. Iron, a very important chemical element in the body of mammals, is the most abundant metal in the brain. It participates in many chemical reactions taking place in the central nervous system acting as a cofactor in key enzymatic reactions involved in neurotransmitter synthesis and degradation, dendritic arborization, and myelination. Moreover, iron accumulation in the brain has been implicated in the pathogenesis of neurogenerative disorders. MATERIAL AND METHODS: The aim of our study was to assess the influence of iron administered orally (30 mg/kg) to rats in the neonatal period (p12-p14) by testing the performance of rats in the open field and social interaction tests, and by evaluating the recognition memory, monoamine levels in some brain structures, and BDNF mRNA expression. The behavioral and biochemical tests were performed in adult p88-p92 rats. RESULTS: Iron administered to rats in the neonatal period induced long-term deficits in behavioral tests in adult rats. It reduced the exploratory activity in the open field test. In the social interaction test, it induced deficits in the parameters studied, and decreased memory retention. Moreover, iron changed the brain monoamine levels in some studied brain structures and decreased the expression of BDNF mRNA in the hippocampus. CONCLUSIONS: All earlier and our present results indicated that iron administered to rats in the neonatal period induced an increase in oxidative stress which resulted in a change in the brain monoamine levels and decreased BDNF mRNA expression which may play a role in iron-induced memory impairment in adult rats.