Albino Mice Research Articles

Study the hepatoprotective effect of the methanolic extract of Plumbago auriculata Lam. against CCl4-induced hepatocyte damage in mice

The liver is an important organ in the body; its diseases are considered the major causes of morbidity and mortality around the world. Hepatotoxic chemicals cause damage to liver cells. Medicinal plants have a powerful hepatoprotective effect. This study has been aimed to assess the potential hepatoprotective effect of the methanolic extract of Plumbago auriculata Lam. against carbon tetrachloride (CCl4)- induced hepatocyte damage in albino mice. The methanolic extract of the plant was subjected to preliminary phytochemical analysis to determine the presence of secondary metabolites according to standard protocols. The acute toxicity study was carried out to measure the LD50. Swiss albino mice were divided into 4 groups treated intraperitoneally (IP) once daily for 7 days; the first group was a negative control, while the second group, considered as a CCl4 model, received a single dose of carbon tetrachloride during the last day. The third group received 500 mg/kg of body weight of methanolic extract of P. auriculata, and the last group received 100 mg/kg of body weight of standard silymarin, after 2 h of treatment, on the last day, all animals (except negative control group) have received CCl4 at a dose of 1 mL/kg of body weight. Biochemical analysis of collected blood and histopathological examination were performed. Results revealed that the preliminary phytochemical screening of the methanolic extract of the plant confirmed the presence of many biologically active secondary metabolites like flavonoids, steroids, terpenoids, saponins, glycosides and phenols and LD50 of the extract was 2.5 g/kg. The CCl4- intoxicated mice showed an increase in biochemical enzyme levels (ALT and AST) compared with the negative control group. The extract of 500 mg/kg revealed a significant reduction (p ? 0.05) in enzyme activities. The histopathological analysis of plant extract and silymarin-treated groups revealed a decrease in the pathological features compared with the CCl4-intoxicated group. It was concluded that the extract of P. auriculata has a significant effect on hepatoprotection against CCl4-induced hepatocyte damage and this may be because of the combined effects of the bioactive compositions of plant extract.

Evaluation of Gastroprotective Activity of the Methanolic Extract of Justicia pectoralis Jacq. (Acanthaceae)

Introduction: Justicia pectoralis Jacq. is traditionally applied in folk medicine in Brazil and in several Latin American countries. The leaves are used in tea form, especially in the treatment of respiratory disorders, acting as an expectorant. It also has activity in gastrointestinal disorders, and it is anti-inflammatory, antioxidant, sedative, and estrogenic, among others. Aims: To investigate the gastroprotective activity of the methanol extract of the leaves of Justicia pectoralis Jacq. (MEJP) in different experimental models of gastric ulcers. Materials and methods: The adult leaves of Justicia pectoralis Jacq. were collected and cultivated in beds, with an approximate spacing of 40 × 40 cm, organic fertilization, irrigation with potable water and without shelter from light. The MEJP was prepared from the dried and pulverized leaves and concentrated under reduced pressure in a rotary evaporator. For the experimental model of gastric ulcer, Swiss male albino mice were used. The inputs used in the experiment were MEJP at three different concentrations (250, 500 and 1000 mg/kg p.o.), cimetidine (50 mg/kg p.o.), indomethacin (50 mg/kg s.c.) and vehicle (10 mL/kg p.o.). Results: MEJP (250, 500 and 1000 mg/kg p.o.) demonstrated gastroprotective activity, with levels of protection of 45.65%, 44.80% and 40.22%, respectively, compared to the control (vehicle). Compared with cimetidine (48.29%), MEJP showed similar gastroprotective activity. Conclusions: This study demonstrated the gastroprotective activity of MEJP and contributes to validate the traditional use the species for gastric disorders and provides a pharmacological basis for its clinical potential.

In vitro and In vivo Studies for Screening of Anti-inflammatory, Thrombolytic and Acute Toxicological Activity in Camellia Chrysantha (Hu) Tuyama

Purpose: The objective of this study was to investigate the impact of methanol-prepared leaves extract of Camellia Chrysantha (Hu) Tuyama. on several in vitro activities, including anti-inflammatory and thrombolytic effects. Additionally, the study aimed to assess the acute toxicological activity of the extracts in an animal model. Place and Duration of Study: The research study was carried out from Nov 2023 to Feb 2024 at the Bangladesh Council of Scientific and Industrial Research (BCSIR), Laboratory of Pharmacology, University of Asia Pacific and the Laboratory of Phytochemistry and Pharmacology, Department of Pharmacy, as well as the Laboratory of Microbiology at Stamford University Bangladesh, Dhaka. Methodology: The methodology involved various doses of methanolic leaves extract of Camellia Chrysantha (Hu) Tuyama, and employed techniques such as the Inhibition of Protein Denaturation Assay for anti-inflammatory test and the clot lysis test for thrombolytic assay. The acute toxicological activity was assessed by Cinnamon oil induced toxicological and administration of acetic acid induced writhing responses in Swiss albino mice. Result: The Inhibition of Protein Denaturation Assay test yielded findings indicating its anti-inflammatory properties against all strains used in this research. The findings from the study examining the anti-inflammatory properties indicate that Chrysantha (Hu) Tuyama exhibits a significant efficacy of 86.54% in inhibiting inflammation at a concentration of 1000 µg/mL. This level of efficacy is comparable to that of acetylsalicylic acid, which also has a similar efficacy of 98.54 % at the same concentration. Thrombolysis test is a controlled laboratory procedure that assesses the ability of plant extracts to dissolve blood clots. The study found that MECCL can reduce blood clots. Table 2 shows that MECCL's thrombolytic potential was 95.69%, which is much higher than the usual value of 91.304%. Our research found that MECCL did not induce any harmful effects in mice during the acute toxicity test, as determined by the toxicological assessment. No signs of illness or death were reported throughout the acute toxicity trial. Conclusion: The Camellia chrysantha (Hu) Tuyama plant exhibits privileged qualities that could lead to the discovery of novel therapeutic substances. It has anti-inflammatory, thrombolytic, and mild acute toxicity properties. Further exploration of this plant could be beneficial. Our study results contribute to the growing body of evidence demonstrating that natural products may potentially have favourable effects on human health.

Prenatal restraint stress affects early neurobehavioral response and oxidative stress in mice pups.

Prenatal stress (PS), in both humans and animals, presents a potential risk to the mother and her fetus throughout gestation. PS is always associated with physiological changes that alter embryonic development and predispose the individual to lifelong health problems, including susceptibility to mental illness. This study aims to identify the harmful effects of prenatal restraint stress (PRS), commonly employed to induce stress painlessly and without any lasting debilitation during gestation. This stress is applied to pregnant Swiss albino mice from E7.5 to delivery for three hours daily. Our results show that PS affects dams' weight gain during the gestational period; moreover, the PS dams prefer passive nursing, exhibit a lower percentage of licking and grooming, and impair other maternal behaviors, including nesting and pup retrieval. Concerning the offspring, this stress induces neurobehavioral impairments, including a significant increase in the time of recovery of the young stressed pups in the surface righting reflex, the latency to avoid the cliff in the cliff avoidance test, longer latencies to accomplish the task in negative geotaxis, and a lower score in swimming development. These alterations were accompanied by increased Malondialdehyde activity (MDA) at PND17 and 21 and downregulation of AchE activity in the whole brain of pups on postnatal days 7 and 9. These findings demonstrated that PS causes deleterious neurodevelopmental impairments that can alter various behaviors later in life.

Phlomis crinita Cav. From Algeria: A source of bioactive compounds possessing antioxidant and wound healing activities

Ethnopharmacological relevancePhlomis crinita Cav. (Lamiaceae), locally known as “El Khayata” or “Kayat El Adjarah”, is traditionally used in Algeria for its wound-healing properties. Aim of the studyInvestigate, for the first time, the phytochemical profile, safety, antioxidant and wound-healing activities of the flowering tops methanolic extract of P. crinita (PCME) collected from Bouira Province in the North of Algeria. Materials and methodsPreliminary phytochemical assays were carried out on PCME to quantify the main classes of bioactive compounds, such as total phenols, flavonoids, and tannins. An in-depth LC-DAD-ESI-MS analysis was carried out to elucidate the phytochemical profile of this plant species. Antioxidant activity was investigated by several colorimetric and fluorimetric assays (DPPH, TEAC, FRAP, ORAC, β-carotene bleaching and ferrozine assay). The acute oral toxicity of PCME (2000 mg/kg b.w.) was tested in vivo on Swiss albino mice, whereas the acute dermal toxicity and wound-healing properties of the PCME ointment (1–5% PCMO) were tested in vivo on Wistar albino rats. Biochemical and histological analyses were carried out on biological samples. ResultsThe phytochemical screening highlighted a high content of phenolic compounds (175.49 ± 0.8 mg of gallic acid equivalents/g of dry extract), mainly flavonoids (82.28 ± 0.44 mg of quercetin equivalents/g of dry extract). Fifty-seven compounds were identified by LC-DAD-ESI-MS analysis, belonging mainly to the class of flavones (32.27%), with luteolin 7-(6″-acetylglucoside) as the most abundant compound and phenolic acids (32.54%), with salvianolic acid C as the most abundant compound. A conspicuous presence of phenylethanoids (15.26%) was also found, of which the major constituent is forsythoside B. PCME showed a strong antioxidant activity with half-inhibitory activity (IC50) ranging from 1.88 to 37.88 μg/mL and a moderate iron chelating activity (IC50 327.44 μg/mL). PCME appears to be safe with Lethal Dose 50 (LD50) ≥ 2000 mg/kg b.w. No mortality or toxicity signs, including any statistically significant changes in body weight gain and relative organs’ weight with respect to the control group, were recorded. A significant (p < 0.001) wound contraction was observed in the 5% PCMO-treated group with respect to the untreated and petroleum jelly groups between 8 and 20 days, whereas no statistically significant results were observed at the two lower doses (1 and 2% PCMO). In addition, the 5% PCMO-treated group showed a statistically significant (p < 0.05) wound healing activity with respect to the reference drug-treated group, showing, at the end of the study, the highest wound contraction percentage (88.00 ± 0.16%). ConclusionPCME was safe and showed strong antioxidant and wound-healing properties, suggesting new interesting pharmaceutical applications for P. crinita based on its traditional use.

Exploring the anticancer potential of double-active pharmaceutical ingredient, metforminium ibuprofenate: Integrating in vivo and in silico investigations

Rationale: A novel double active pharmaceutical ingredient (d-API), metforminium ibuprofenate (MtHIb) was synthesised by combining metformin hydrochloride (MtHCl) and sodium ibuprofen (NaIb). This formulation exhibits anti-diabetic and anti-inflammatory properties similar to its parent compounds, along with a remarkable antiproliferative effect on diverse cancer cells. AimThe present study is aimed to analyse the anticancer potential of MtHIb by mouse tumour model and molecular docking. MethodsSolid tumour was induced by Dalton's Lymphoma Ascites (DLA) cells in Swiss albino mice, and d-API was administered orally. The tumour volume was measured using Vernier calliper and the activity of γ-glutamyl transferase (GGT) was assessed. The potential interactions of MtHIb with target proteins mTOR, HER2, EGFR, CDK4, CDK6, ERα/β, progesterone, COX2, BUB1, and KEAP2 were analyzed in silico. ResultsA significant reduction in tumour size was observed in mice treated with MtHIb. On the 30th day, the tumour volume, which was 8.12 cm3 in untreated animals, decreased to 1.311 cm3 with the treatment of 5 mg/kg b.wt of MtHIb, representing an 83.8 % reduction. The activity of GGT, a marker enzyme of proliferative activity, was considerably reduced from 394.87 to 51.26 U/mg protein/L. Molecular docking studies indicated that MtHIb exhibited strong binding affinity towards all the screened target proteins, specifically HER2, EGFR, CDK4, and BUB1. DiscussionThe findings suggest that MtHIb has promising anti-tumour effect, as evidenced by its significant reduction in tumour size and GGT activity in mice. The strong binding affinity of MtHIb towards the key cancer related proteins further supports its potential as a therapeutic agent against cancer, particularly in targeting pathways involved in cell proliferation and survival. Further preclinical and clinical studies are required to validate these findings and to explore the full therapeutic potential of MtHIb in cancer treatment.

Effects of Repeated Doses of the Vero Cell Vaccine (SARS-Cov-2 Inactivated Vaccine) on Renal Functions in Balb/C Albino Mice.

Many of the vaccines developed for COVID-19 have been approved for clinical emergency use before their safety and preclinical studies have been completed. The main aim of this study was to investigate the effects of an inactivated SARS-CoV-2 virus vaccine (Vero cells) on renal function in Balb/C Albino mice. 21 healthy, 6-8 week old BALB/c male mice were divided into three equal groups, and 0.10 mL of intramuscular saline equal to the vaccine dose volume was administered to the first group. To the second group, a single dose of 0.10 mL 120 U of Vero cell inactive SARS COV-2 vaccine was administered intramuscularly. Group 3 received two consecutive doses of 0.10 mL 120 U intramuscular Vero cell inactive SARS COV-2 vaccine, 14 days apart. After administration, the clinical status, fecal and urine status, nutritional status and kidney histopathology of the mice were evaluated. It was determined that no acute toxic symptoms were observed in the mice administered the vaccine, they were in good condition, and there was no significant stimulatory reaction related to the vaccine in the tissues of the injected local area. There was no difference in feed consumption, water consumption, and body weight gains between the control group, the groups that received a single dose of vaccine, and the groups that received two doses of vaccine (p>0.05). No difference was found between the groups when urine and feces amounts were compared (p>0.05). No difference was found between the groups when urinary urea, creatinine, and serum BUN, creatinine levels were compared (p>0.05). No difference was found in the histopathological evaluation of the kidneys between the groups (p>0.05). In conclusion, single or repeated injections of the SARS-CoV-2 vaccine (Vero cells) into mice were found to have no adverse effects on the animals' overall clinical health, performance abilities and kidneys.

Cytokine storm modulation using cholecalciferol and low dose gamma radiation in Escherichia coli infected mice.

This work investigates the efficiency of cholecalciferol and low dose gamma radiation in modulating cytokine storm through their impact on inflammatory and anti-inflammatory cytokine and protecting against lung and liver injuries. Male Swiss albino mice were exposed to 0.2 Gy gamma radiation/week for four consecutive weeks then injected intraperitoneally (i.p) with a single dose of 8.3 × 106 CFU Escherichia coli/g b.w. then injected i.p. with 1.0 mg/kg cholecalciferol (Vit D3) for 7 days starting 4 h after E. coli injection. The results revealed that Cholecalciferol and low dose gamma radiation caused significant depletion in the severity of E. coli infection (colony forming unit per milliliter), log10 of E. coli, Tumor necrosis factor alpha, Interleukin 6, VEGF, alanine aminotransferase, and aspartate aminotransferase levels and significant elevation in IL-10, IL-4, and HO-1. Immunohistochemical analysis of caspase-3 expression in lung tissue section showed low caspase-3 expression in cholecalciferol and low dose gamma radiation treated group. Histopathological examinations were performed in both lung and liver tissues which also emphasis the biochemical findings. Our results exhibit the importance of cholecalciferol and low dose gamma radiation in improving liver function and providing anti-inflammatory response in diseases causing cytokine storm.

Phytic acid attenuates acetaminophen-induced hepatotoxicity via modulating iron-mediated oxidative stress and SIRT-1 expression in mice

Introduction: Administration of high doses of acetaminophen (APAP) results in liver injury. Oxidative stress and iron overload play roles in the pathogenesis of APAP-induced hepatotoxicity. The present study assessed the potential hepatoprotective effects of phytic acid (PA), a natural antioxidant and iron chelator, on APAP-induced hepatotoxicity and the possible underlying mechanism through its effects on CYP2E1 gene expression, iron homeostasis, oxidative stress, and SIRT-1 expression levels.Methods: Twenty-four adult male albino mice were used in this study. Mice were divided into four groups (six mice in each group): control, APAP-treated, PA-treated and APAP + PA-treated groups. Liver function tests, serum and liver tissue iron load were evaluated in all the study groups. Hepatic tissue homogenates were used to detect oxidative stress markers, including malondialdehyde (MDA) and reduced glutathione (GSH). Histological hepatic evaluation and immunohistochemistry of SIRT-1 were performed. Quantitative real-time PCR was used for the assessment of CYP2E1 and SIRT-1 gene expressions. APAP-induced biochemical and structural hepatic changes were reported.Results: PA administration showed beneficial effects on APAP-induced hepatotoxicity through improvements in liver functions, decreased CYP2E1 gene expression, decreased serum and liver iron load, decreased MDA, increased GSH, increased SIRT-1 expression level and improvement in hepatic architecture.Conclusion: Conclusively, PA can be considered a potential compound that can attenuate acetaminophen-induced hepatotoxicity through its role as an iron chelator and antioxidant, as well as the up-regulation of SIRT-1 and down-regulation of CYP2E1.

Supplementation of Salvia hispanica L. seed ameliorated liver function enzymes, hyperlipidemia, and oxidative stress in high fat diet fed Swiss albino mice

Supplementation of Salvia hispanica L. seed ameliorated liver function enzymes, hyperlipidemia, and oxidative stress in high fat diet fed Swiss albino mice

Determination of the effects of sunset yellow on mouse liver and pancreas using histological methods.

Sunset Yellow (SY) is an azo synthetic food dye. Although the amount of SY consumed varies in different periods of life, it increases especially in children and adolescents. It may cause pathologic effects in organs at early ages. The aim of this study was to determine the effects of SY on the liver and pancreas of mice of different age groups using histological methods. The study included Swiss albino mice that were divided into three treatment groups and three control groups based on age (4, 8, and 10weeks old), with six mice in each group (n=6/group). SY was administered at 30mg/kg/bw/week orally for 28days to treatment groups. The liver and pancreas tissues were kept in 10% formaldehyde, then passed through alcohol and xylene series and stained with Hematoxylin-Eosin. They were evaluated using light and electron microscopy. In SY groups, the mean body weight (p: 0.026) and the mean liver weight (p: 0.013) of the mice increased, and their mean pancreas weight decreased (p: 0.045).The numbers of degenerative cells in the liver tissues of the mice in the SY groups were high. Severe dilation in the sinusoids and haemorrhages focused around the Vena Cava were detected. In the pancreatic tissues of the SY groups, increases in fibroblasts and lymphocytic infiltration were observed. Pathologies interpreted as chronic pancreatitis were more intense in the weaning group (4weeks old). SY may be more harmful at an early age, and it may be beneficial to limit its use during this period.

Effects of Oral Zinc Supplementation on Early Embryonic Development and Neonates of Aged Female Albino Mice

     Female reproductive aging is a normal phase of life that eventually leads to menopause and reproductive senescence. The current experimental investigation was intended to study zinc supplementation effects on early embryonic development and neonates in 26-28 weeks old female mice. In this investigation, 80 mature female mice were used that were divided into two groups of forty each. Two control groups received distilled water, while two Zn groups were given 0.115 mg/kg/day Zn orally daily during 2-3 estrous cycles. The female mice were all mated with adult males. Twenty female mice from both the control and Zn groups were euthanized by CO2 gas inhalation, and then a longitudinal incision in the abdomen of each female mouse was performed and uterine horns and oviducts were detached from the body in order to obtain two-cell embryos. On the other hand, 20 pregnant mice from each group were permitted to complete their pregnancy until birth and then their neonates were collected for macroscopic examination. The findings showed that the Zn supplementation significantly (P≤0.01) improved the mean embryonic development and the quality of 2-cell stage embryo grade A. Whereas, it decreased the mean embryonic development of 2-cell stage embryo grade D in aged female mice significantly (P≤0.01) in comparison with aged control groups. Also, the count and quality of neonates from Zn-treated aged female mice enhanced significantly (P≤0.01) as compared to non-treated aged female mice. It was concluded from these findings that the Zn can improve embryonic development and neonate count and quality in aged mice.

Evaluation of the Pharmacological Potential of Nyctanthes Arbor-Tristis Flowers Extract against Milk Induced Asthmatic Disorder in Swiss Albino Mice

Asthma disease and its complications remain the cause of significant morbidity worldwide, representing a major burden for health care resources. Although potent anti-asthmatic drugs are available, most of them produce several toxicities, thus emphasizing the need to search for new alternatives. Therefore, the present study was designed to evaluate the anti-asthmatic activity of flowers extract of Nyctanthes Arbor-tristis using milk induced leucocytosis and eosinophilia in mice. Hydro-ethanolic extract of dried flower of Nyctanthes Arbor-tristis was prepared by maceration and used in the dose of 100 mg/kg and 200mg/kg; (p.o.). In-vivo model milk induced leucocytosis and eosinophilia mice were used for evaluating anti-asthamatic activity of the drug. The total leucocyte and eoisinophil count in disease control group was significantly higher as compared to hydro ethanolic extract of Nyctanthes arbor-tristis group IV, group V and Standard treatment group III with Mepyramine (&lt; 0.05). Hydro ethanolic extract of Nyctanthes arbor-tristis at dose of 200mg/kg and Standard treatment with Mepyramine at dose of 8 mg/kg, p.o. shown statistical significant and positive inhibition was seen with leukocyte count 1640±142, 1230±175 and eosinophil count 68.83±1.22, 57±18.35. However, hydro-ethanolic extract of the drug showed a significant inhibition was observed in milk induced leucocytosis and eosinophilia. Thus, hydro-ethanolic extract of dried flower of Nyctanthes Arbor-tristis have significant anti-asthmatic activity.

The Effect of Cerium Oxide (CeO2) on Ischemia-Reperfusion Injury in Skeletal Muscle in Mice with Streptozocin-Induced Diabetes

Objective: Lower extremity ischemia-reperfusion injury (IRI) may occur with trauma-related vascular injury and various vascular diseases, during the use of a tourniquet, in temporary clamping of the aorta in aortic surgery, or following acute or bilateral acute femoral artery occlusion. Mitochondrial dysfunction and increased basal oxidative stress in diabetes may cause an increase in the effects of increased reactive oxygen species (ROS) and mitochondrial dysfunction due to IRI. It is of great importance to examine therapeutic approaches that can minimize the effects of IRI, especially for patient groups under chronic oxidative stress such as DM. Cerium oxide (CeO2) nanoparticles mimic antioxidant enzymes and act as a catalyst that scavenges ROS. In this study, it was aimed to investigate whether CeO2 has protective effects on skeletal muscles in lower extremity IRI in mice with streptozocin-induced diabetes. Methods: A total of 38 Swiss albino mice were divided into six groups as follows: control group (group C, n = 6), diabetes group (group D, n = 8), diabetes–CeO2 (group DCO, n = 8), diabetes–ischemia/reperfusion (group DIR, n = 8), and diabetes–ischemia/reperfusion–CeO2 (group DIRCO, n = 8). The DCO and DIRCO groups were given doses of CeO2 of 0.5 mg/kg intraperitoneally 30 min before the IR procedure. A 120 min ischemia–120 min reperfusion period with 100% O2 was performed. At the end of the reperfusion period, muscle tissues were removed for histopathological and biochemical examinations. Results: Total antioxidant status (TAS) levels were found to be significantly lower in group DIR compared with group D (p = 0.047 and p = 0.022, respectively). In group DIRCO, total oxidant status (TOS) levels were found to be significantly higher than in group DIR (p &lt; 0.001). The oxidative stress index (OSI) was found to be significantly lower in group DIR compared with group DCO (p &lt; 0.001). Paraoxanase (PON) enzyme activity was found to be significantly increased in group DIR compared with group DCO (p &lt; 0.001). The disorganization and degeneration score for muscle cells, inflammatory cell infiltration score, and total injury score in group DIRCO were found to be significantly lower than in group DIR (p = 0.002, p = 0.034, and p = 0.001, respectively). Conclusions: Our results confirm that CeO2, with its antioxidative properties, reduces skeletal muscle damage in lower extremity IRI in diabetic mice.

Protective effects of gallic acid against nickel-induced kidney injury: impact of antioxidants and transcription factor on the incidence of nephrotoxicity

Nickel (Ni) is a common metal with a nephrotoxic effect, damaging the kidneys. This study investigated the mechanism by which gallic acid (GA) protects mice kidneys against renal damage induced by Nickel oxide nanoparticles (NiO-NPs). Forty male Swiss albino mice were randomly assigned into four groups, each consisting of ten mice (n = 10/group): Group I the control group, received no treatment; Group II, the GA group, was administrated GA at a dosage of 110 mg/kg/day body weight; Group III, the NiO-NPs group, received injection of NiO-NPs at a concentration of 20 mg/kg body weight for 10 consecutive days; Group IV, the GA + NiO-NPs group, underwent treatment with both GA and NiO-NPs. The results showed a significant increase in serum biochemical markers and a reduction in antioxidant activities. Moreover, levels of 8-hydroxy-2’-deoxyguanosine (8-OH-dG), phosphorylated nuclear factor kappa B (p65), and protein carbonyl (PC) were significantly elevated in group III compared with group I. Furthermore, the western blot analysis revealed significant high NF-κB p65 expression, immunohistochemistry of the NF-κB and caspase-1 expression levels were significantly increased in group III compared to group I. Additionally, the histopathological inspection of the kidney in group III exhibited a substantial increase in extensive necrosis features compared with group I. In contrast, the concomitant coadministration of GA and NiO-NPs in group IV showed significant biochemical, antioxidant activities, immunohistochemical and histopathological improvements compared with group III. Gallic acid has a protective role against kidney dysfunction and renal damage in Ni-nanoparticle toxicity.

Antinociceptive Evaluation of Antidepressants (Cita- lopram, Duloxetine and Amitriptyline) in a Mouse Model of Acute Pain

Introduction: Acute pain is a pervasive and debilitating symptom affecting the general population as well as depressed patients who suffer even more from pain and fatigue. Aims and Objectives: To evaluate the antinociceptive effect induced by antidepressants (Citalopram, Duloxetine and Amitriptyline) in acute pain induced in mice. Place and Duration of study: Animal Research Laboratory of University of Lahore. Study Period: 2018- 2019 Material and Methods: An experimental animal study was carried out on 25 albino mice. The mice were divided into 5 groups; Group 1: Positive Control (PC), Group 2: Ibuprofen (IBO) (Standard) 80mg/kg, Group3: Citalopram (CTP)3mg/kg, Group 4: Duloxetine (DXT) 25mg/kg, Group 5: Amitriptyline (AMT) 15mg/kg. Groups 2-5 were administered drugs orally through a feeding tube as per group designation while Group 1: Control was given an equivalent amount of normal saline. One hour post treatment with test drugs, all Groups (1-5) were injected 10 ml/ kg of 2% acetic acid I/P and number of writhing movements consisting of contraction of abdominal muscles leading to extension of hind limb and periodic arching of body as well as paw licking behavior were counted for 20 minutes at 5- minute interval, using hand tally counter. Degree of analgesia was calculated by using formula of percentage effectiveness. Data was entered and analyzed utilizing SPSS version 21, p?0.05 was taken as significant. Results: Ibuprofen completely eliminated the nociceptive outcome of diluted acetic acid in writhing and licking of experimental animals. Citalopram, showed maximum decreasing effect (95%-96%) in writhing in 5-20 min. However, its effect in paw licking was low. Duloxetine showed 70% to 90% decrease in writhing at 5-20 min whereas 100 % inhibition of paw-licking was observed at 5 to 20 minutes. The writhing effect of amitriptyline was 77%-90% at 5-20 min and paw licking effect was 80-90 % at 5-20 min. Conclusion: Amitriptyline, duloxetine and citalopram have significant effect in reducing the acute nociceptive pain and may be utilized as analgesic in acute state of pain.

Natural deep eutectic liquid and ultrasound-assisted extraction of milk thistle phenolics and their hepatoprotective activities

IntroductionThe present research describes the utilization of natural deep eutectic solvent in combination with ultrasound for the extraction of milk thistle polyphenols. The extracts obtained under different conditions were evaluated for their in vitro antioxidant activities and hepatoprotective activities in Albino mice (in vivo).MethodsThe extraction parameters involving liquid-to-solid ratio (S/L), ethanol-to-natural deep eutectic solvent ratio (EtOH/DES), extraction time (t), and ultrasound treatment time were investigated and optimized to enhance the recovery of bioactives, their phenolic content, Trolox equivalent antioxidant capacity (TEAC), and radical scavenging capacity (RSC).Results and discussionsThe extraction of milk thistle polyphenols using glucose/citric acid (1:1)-based natural deep eutectic liquid coupled with ultrasound for 1.0 min under an S/L of 6.2, EtOH/DES 9, and extraction time of 120.8 min offered 35.89 ± 2.29 g/100 g of crude extracts, which were three-fold higher than that by conventional solvent extraction (CSE). Each gram of milk thistle extracts thus obtained comprised 377.93 ± 6.17 mg GAE of TPC and exhibited 298.70 ± 3.06 μmol TEAC and 93.16 ± 0.58 percent inhibition of DPPH free radicals. In addition, the administration of milk thistle extracts obtained as given above at 25 mg/Kg body weight in Albino mice significantly (p ≤ 0.05) improved the liver function parameters at the end of treatment (7 days).ConclusionOverall, it was observed that NaDES in combination with medium-level ultrasound energy (700 watt) might work as a sustainable choice to enhance the recovery of bioactive phenolics from milk thistle powder without compromising their antioxidant and hepatoprotective potential.

Toxicity study and ameliorative effects of the aqueous leaf extract of Lecanoidiscus cupanioides Planch (ex. Benth) on the stress-induced ulcer

Lecaniodiscus cupanioides Planch (ex. Benth) is effective in treating burns, fevers, and inflammatory conditions. This study investigates the toxicity effects of the aqueous leaf extract (ALE) of L. cupanioides and its effect on stress-induced ulcers in animal models. The plant was collected and a 1:30 (g/ml) plant powder/solvent ratio was extracted using an ultrasonic bath at 50 °C for 45 min. Up-and-down procedure was used for acute toxicity. During subacute toxicity testing, a total of 20 mice were divided into four groups of five animals each. While group 1 served as control, groups 2, 3, and 4 received 250, 500, and 1000 mg/kg of the extract daily for 21 days. On day 22nd, animals were sacrificed and samples were collected for hematology, biochemical, and histological analyses. In the stress-induced ulcer activity, male albino mice were randomly separated into 5 groups of 5 animals, treated with the test drug, and then dissected after being stressed using the water immersion model. LD50 was &gt; 5000 mg/kg, and in biochemical examination, there was a significant decrease in the ALP level at medium and high doses (p value &lt; 0.05) and non-significant alterations in the values of urea, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), body weight and hematology parameters (p &gt; 0.05). The histology results showed no evidence of liver and kidney toxicity. In conclusion, aqueous leaf extract of L. cupanioides was safe following a single dose (at 5000 mg/kg) and following repeated doses for 21 days (at 250, 500, and 1000 mg/kg). This study demonstrated that the extract had a significant effect on stress-induced ulcers at various dose levels when compared to the control (native, negative control, and omeprazole). The animals treated with 200mg/kg and 400mg/kg of the extract showed a significant increase in ulcer score, ulcer index, ulcer severity, and total acidity (p &lt; 0.05). The ulcer protection ability of the aqueous plant extract was dose-dependent.

Safety, Analgesic, and Anti-Inflammatory Effects of Aqueous and Methanolic Leaf Extracts of Hypericum revolutum subsp. keniense

In light of the enduring obstacles encountered in analgesia and anti-inflammatory therapeutics despite the strides made in contemporary medical sciences, the quest for alternative efficacious strategies is an imperative pursuit. Thus, this study investigated the safety profiles, as well as the analgesic and anti-inflammatory attributes, of aqueous and methanolic leaf extracts derived from Hypericum revolutum subsp. keniense—a botanical entity entrenched in historical ethnomedicinal practices in the Kenyan context. The assessment of acute oral toxicity of these extracts was conducted in accordance with the Up- and-Down method advocated by the Organisation for Economic Cooperation and Development (OECD), utilizing Swiss albino mice as the experimental subjects. Subsequent investigation entailed the evaluation of antinociceptive and anti-inflammatory properties employing the acetic acid-induced writhing and carrageenan-induced paw oedema methodologies, respectively, in the same murine model. The findings of this study evince the safety of both aqueous and methanolic extracts, with LD50 values surpassing 2000 mg/kg body weight and the absence of discernible signs of toxicity. Furthermore, a notable dose-dependent (P&lt;0.05) manifestation of analgesic effects was observed for both extracts, with the aqueous variant demonstrating heightened potency compared to its methanolic counterpart (P&lt;0.05). Moreover, the anti-inflammatory efficacy escalated significantly with escalating extract doses and prolonged treatment duration (P&lt;0.05), wherein the aqueous extract showcased superior effectiveness vis- à-vis the methanolic extract across all dosage regimens and temporal checkpoints (P&lt;0.05). Therefore, this investigation underscores the latent promise of the examined extracts as reservoirs of safe and efficacious analgesic and anti-inflammatory agents, thereby meriting further meticulous exploration. Subsequent research endeavours ought to pivot towards elucidating the phytochemical constituents underpinning the observed effects, alongside unravelling their mechanistic underpinnings across a spectrum of animal models and clinical milieus.

Repeated dose toxicity studies of Trichostatin A in Swiss albino mice through oral and intravenous route of administration with special emphasis on genotoxicity

Intravenous and oral 14 d repeated dose toxicity studies of Trichostatin A (TSA) were carried out in Swiss albino mice using low, intermediate, and high doses. Intravenous doses were 10, 25, and 50 μg/kg b.w while the oral doses were 20, 50, and 100 μg/kg b.w. Respective control groups of mice were administered phosphate buffered saline (vehicle only) for 14 consecutive days. All external morphological, hematological, biochemical, urine, histopathological, food intake in addition to body weight and vital organ weight were recorded. During the study no mortality in any animal was observed in either treatment routes. There were no significant changes in morphology, food intake, hematology, biochemical, urine analysis, organ weight. Animals treated high dose of TSA intravenously (50 μg/kg b.w) and orally (100 μg/kg b.w) had enlarged, congested, and discolored kidneys which were statistically significant. Histopathological studies had shown statistically significant degenerated glomerulus in high dose of intravenous and orally treated animals and degenerated tubule were found in orally treated animals. Genotoxicity was evaluated using micronucleus frequency at 14 and 21 d after treatment and chromosomal aberration at 21 d after treatment. Micronucleaus assay and chromosomal assay however did not show any significant changes at any doses and administration routes. Therefore, this study concludes that dose ∼25 µg/kg and ∼50 µg/kg b.w may be considered as No Observed Adverse Effect Level (NOAEL) for intravenous and oral administration of TSA respectively.