Adult Swiss Albino Mice Research Articles

Vitamin K2 Ameliorates Diabetes-Associated Cognitive Decline by Reducing Oxidative Stress and Neuroinflammation.

Diabetes, a chronic metabolic disease, affects approximately 422million people and leads to 1.5million deaths every year, It is found that 45% of individuals with diabetes eventually develop cognitive impairment. Here we study effects of Vitamin K2 on diabetes-associated cognitive decline (DACD) and its underlying mechanism. Diabetes was induced in adult Swiss albino mice with high-fat diet and a low dose (35mg/kg) of streptozotocin and measured by fasting glucose and HbA1c levels. After one week of development of diabetes, one group of animals received Vitamin K2 (100µg/kg) via oral gavage for 21 days. Then different behavioural studies, including the elevated plus maze, Morris water maze, passive avoidance test and novel object recognition test were performed followed by biochemical tests including AchE, different oxidative stress parameters (SOD, GSH, MDA, catalase, SIRT1, NRF2), inflammatory markers (TNFα, IL1β, MCP1, NFκB), apoptosis marker (Caspase 3). Hippocampal neuronal density was measured using histopathology. Vitamin K2 treatment in diabetic animals led to reduced fasting glucose and HbA1c, It could partially reverse DACD as shown by behavioural studies. Vitamin K2 adminstration reduced corticohippocampal AchE level and neuroinflammation (TNFα, IL1β, MCP1, NFκB, SIRT1). It reduced oxidative stress by increasing antioxidant enzymes (SOD, GSH, catalase), transcription factor NRF2 while reducing caspase 3. This eventually increased CA1 and CA3 neuronal density in diabetic animals. Vitamin K2 partially reverses DACD by increasing ACh while reducing the oxidative stress via Nrf2/ARE pathway and neuroinflammation, thus protecting the hippocampal neurons from diabetes associated damage.

Metformin augments major cytoplasmic organization except for spindle organization in oocytes cultured under hyperglycemic and hyperlipidemic conditions: An in vitro study

The present study aimed to investigate the role of antidiabetic drug metformin on the cytoplasmic organization of oocytes. Germinal vesicle (GV) stage oocytes were collected from adult female Swiss albino mice and subjected to in vitro maturation (IVM) in various experimental groups- control, vehicle control (0.3% ethanol), metformin (50 μg/mL), high glucose and high lipid (HGHL, 10 mM glucose; 150 μM palmitic acid; 75 μM stearic acid and 200 μM oleic acid in ethanol), and HGHL supplemented with metformin. The metaphase II (MII) oocytes were analyzed for lipid accumulation, mitochondrial and endoplasmic reticulum (ER) distribution pattern, oxidative and ER stress, actin filament organization, cortical granule distribution pattern, spindle organization and chromosome alignment. An early polar body extrusion was observed in the HGHL group. However, the maturation rate at 24 h did not differ significantly among the experimental groups compared to the control. The HGHL conditions exhibited significantly higher levels of oxidative stress, ER stress, poor actin filament organization, increased lipid accumulation, altered mitochondrial distribution, spindle abnormalities, and chromosome misalignment compared to the control. Except for spindle organization, supplementation of metformin to the HGHL conditions improved all the parameters (non-significant for ER and actin distribution pattern). These results show that metformin exposure in the culture media helped to improve the hyperglycemia and hyperlipidemia-induced cytoplasmic anomalies except for spindle organization. Given the crucial role of spindle organization in proper chromosome segregation during oocyte maturation and meiotic resumption, the implications of metformin's limitations in this aspect warrant careful evaluation and further investigation.

Expression profiling of stemness markers in testicular germline stem cells from neonatal and adult Swiss albino mice during their transdifferentiation in vitro

BackgroundSpermatogonial stem cells (SSCs) were considered to be stem cells with limited potencies due to their existence in adult organisms. However, the production of spermatogonial stem cell colonies with broader differentiation capabilities in primary germ cell cultures from mice of select genetic backgrounds (C57BL6/Tg14, ddY, FVB and 129/Ola) indicated that SSCs from these strains were pluripotent.MethodsWe established primary cultures of SSCs from neonatal and adult Swiss 3T3 Albino mice. Stemness of SSC colonies were evaluated by performing real-time PCR and immunofluorescence analysis for a panel of chosen stemness markers. Differentiation potentials of SSCs were examined by attempting the generation of embryoid bodies and evaluating the expression of ectodermal, mesodermal and endodermal markers using immunofluorescence and real-time PCR analysis.ResultsSpermatogonial stem cells from neonatal and mature mice testes colonised in vitro and formed compact spermatogonial stem cell colonies in culture. The presence of stem cell markers ALPL, ITGA6 and CD9 indicated stemness in these colonies. The differentiation potential of these SSC colonies was demonstrated by their transformation into embryoid bodies upon withdrawal of growth factors from the culture medium. SSC colonies and embryoid bodies formed were evaluated using immunofluorescence and real-time PCR analysis. Embryoid body like structures derived from both neonatal and adult mouse testis were quite similar in terms of the expression of germ layer markers.ConclusionThese results strongly suggest that SSC-derived EB-like structures could be used for further differentiation into cells of interest in cell-based therapeutics.

Effects of sevoflurane and fullerenol C60 on lower limb ischemia-reperfusion injury in streptozocin-induced diabetic mice.

Ischemia-reperfusion injury (IRI) poses a significant challenge for physicians, necessitating the management of cell damage and the preservation of organ functions. Various surgical procedures, such as vascular surgery on extremities, temporary cross-clamping of the abdominal aorta in aortic surgery, and the use of a tourniquet in extremity surgeries, may induce lower limb IRI. The susceptibility to IRI is heightened in individuals with diabetes. This study aimed to investigate the effects of fullerenol C60 and sevoflurane on mouse muscle tissue in a lower limb IRI model and to assess their potential in preventing complications arising from ischemia-reperfusion in mice with streptozocin-induced diabetes. A total of 36 adult Swiss albino mice were randomly divided into six groups, each consisting of six mice: control group (group C), diabetes group (group D), diabetes-ischemia/reperfusion group (group DIR), diabetes-ischemia/reperfusion-fullerenol C60 group (group DIR-FC60), diabetes-ischemia/reperfusion-sevoflurane group (group DIR-S), and diabetes-ischemia/reperfusion-sevoflurane-fullerenol C60 group (DIR-S-FC60). Streptozocin (55 mg/kg) was intraperitoneally administered to induce diabetes in the relevant groups, with mice displaying blood glucose levels of 250 mg/dL or higher at 72 h were considered diabetic. After 4 weeks, all groups underwent laparotomy under anesthesia. In DIR-FC60 and DIR-S-FC60 groups, fullerenol C60 (100 mg/kg) was intraperitoneally administrated 30 min before the ischemia period. Sevoflurane, delivered in 100% oxygen at a rate of 2.3% and 4 L/min, was administered during the ischemia period in DIR-S and DIR-S-FC60 groups. In the IR groups, a microvascular clamp was placed on the infrarenal abdominal aorta for 120 min during the ischemia period, followed by the removal of the clamp and a 120-min reperfusion period. At the end of the reperfusion, gastrocnemius muscle tissues were removed for histopathological and biochemical parameter examinations. Histopathological examination revealed a significant reduction in the disorganization and degeneration of muscle cells in the DIR-S-FC60 group compared to the DIR group (p = 0.041). Inflammatory cell infiltration was notably lower in the DIR-S, DIR-FC60, and DIR-S-FC60 groups than in the DIR group (p = 0.031, p = 0.011, and p = 0.013, respectively). The total damage scores in the DIR-FC60 and DIR-S-FC60 groups were significantly lower than in the DIR group (p = 0.018 and p = 0.008, respectively). Furthermore, the levels of malondialdehyde (MDA) in the DIR-S, DIR-FC60, and DIR-S-FC60 groups were significantly lower than in the DIR group (p < 0.001, p < 0.001, and p < 0.001, respectively). Catalase (CAT) enzyme activity in the DIR-S, DIR-FC60, and DIR-S-FC60 groups was higher than in the DIR group (p = 0.001, p = 0.014, and p < 0.001, respectively). Superoxide dismutase (SOD) enzyme activity in the DIR-FC60 and DIR-S-FC60 groups was also higher than in the DIR group (p < 0.001 and p = 0.001, respectively). Our findings indicate that administering fullerenol C60 30 min prior to ischemia in diabetic mice, in combination with sevoflurane, led to a reduction in oxidative stress and the correction of IR-related damage in muscle tissue histopathology. We believe that the administration of fullerenol C60 before IR, coupled with sevoflurane administration during IR, exerts a protective effect in mice.

Effects of Vitamin B on experimentally induced gastric ulcers in rodents

Background: Peptic ulcer disease (PUD) is associated with water soluble vitamin deficiencies. B group vitamins play vital roles in maintenance of essential body functions. PU patients are found to present with Vitamin B deficiency and high rates of Helicobacter pyloric infection. This study aims to investigate the effect of vitamin B (VB) on experimentally induced gastric ulcers in mice Method: Gastric ulcers were induced in adult Swiss albino mice using absolute ethanol, a nonsteroidal anti-inflammatory agent, diclofenac and acetic acid. Animal were treated for 7 days with vitamin B at 12.5, 25 and 50 mg/kg before ulcer induction with ethanol and diclofenac, while in the acetic acid induced ulcers, treatment (VB 50 mg/kg) was administered for 14 and 28 days post ulcer induction. The degree of gastric ulceration was scored after which tissues subjected to histological analysis Results: The results showed that vitamin B ameliorated ulceration caused by absolute ethanol, diclofenac and acetic acid. In the ethanol induce ulcer, pretreatment with VB produced dosedependent reduction in severity of ulcer when compared to control group. Ulceration of gastric mucosa was inhibited by 3.57%, 23.86% and 55.71% at 12.5, 25 and 50 mg/kg of VB respectively. Omeprazole produced an inhibition of 69.71% at 20mg/kg. VB similarly inhibited diclofenac induced ulceration by 54.31%, 69.05% and 78.94% respectively at tested doses, while omeprazole had 87.79%. For the acetic acid-induced ulcer animals, treatment significantly increased pH of gastric contents when compared with control. Histological analysis revealed dose-dependent (ethanol and diclofenac) and time - dependent (Acetic acid) decrease in severity of damage caused by the ulcerogens on treatment with VB Conclusion: These findings suggest that vitamin B possesses potential gastro-protective effects.

Evaluation of the Efficacy of Artemether/Lumefantrine/Doxycycline Combination against Plasmodium berghei in Mice

Background: Malaria is common in regions like sub-Saharan Africa and South East Asia, where it results in millions of mortalities per year. Resistance to currently available antimalarials further compounds the problem. Drug combination has been demonstrated to be effective in overcoming resistance to antimalarials. This study aimed to assess the efficacy of the combination of Artemether/Lumefantrine (AL) and Doxycycline (DX) against Plasmodium berghei infection in mice. Methods: Thirty Adult Swiss albino mice were inoculated with the chloroquine (CQ)-sensitive P. berghei NK65 strain. The curative test involved oral administration of any of DX, AL, AL/DX, or Chloroquine (CQ) to mice with established infections, while the suppressive test was performed by treating mice shortly after parasite inoculation. Parasitemia levels were monitored using thin smears stained with Giemsa solution. Mean Survival Time (MST) was determined for each group. Results: In the curative test, DX, AL, and AL/DX exhibited parasitemia inhibitions of 81.4%, 94.5%, and 93.2%, respectively, while CQ achieved 93.5% inhibition. MST was significantly extended by DX, AL, and AL/DX treatments compared to negative control (NC). In the suppressive test, parasitemia inhibitions were 79.9%, 96.1%, 95.5%, and 94.9% for DX, AL, AL/DX, and CQ, respectively. The administration of DX, AL, and AL/DX also significantly prolonged MST compared to NC. Conclusion: The study demonstrates that the drug combination, particularly AL/DX, exhibits significant antimalarial effects in both curative and suppressive tests. The combination treatments led to substantial reductions in parasitemia levels and extended mean survival time, indicating their potential as effective antimalarial strategies. These findings highlight the promising role of drug combinations in addressing malaria infections and suggest avenues for further investigation and development of combination therapies.

Repurpose of Mefloquine-Cotrimoxazole Combination as Anti-Plasmodial Agents in Mice Infected with Pasmodium Berghei

The keystone for the treatment of malaria is artemisininbased combination therapy (ACT). The vulnerability of parasites to ACT has, regrettably, declined. Determining new medications or drug combinations that would mitigate parasite resistance is therefore pertinent. Thisstudy assessed the antimalarial property of mefloquinecotrimoxazole in parasitized mice. Thirty adult Swiss albino mice of (18-30g) were grouped into five of 6 mice each. All the mice were inoculated with Plasmodium berghei and orally treated. Group 1 was not treated while groups 2,3, 4 and 5 were treated with chloroquine (10mg/ kg), mefloquine (10mg/kg), cotrimoxazole (10mg/kg) and a combination of mefloquine/cotrimoxazole (10mg/ kg) respectively for five (5) days. The mean survival timewas determined and blood samples were collected and evaluated for percentage parasitemia, hematological and biochemical markers. The results showed that mefloquine/cotrimoxazole combination significantly (p&lt;0.05) reduced percentage parasitemia when compared with single doses of cotrimoxazole and mefloquine. Curatively, cotrimoxazole, mefloquine and mefloquine /cotrimoxazole combination produced 84.90%, 98.95% and 96.96% respectively, whencontrasted with the 90.84% delivered by chloroquine. Suppressively, cotrimoxazole, mefloquine, mefloquine /cotrimoxazole combination, delivered 84.62%, 90.20% and 97.55% respectively. The prophylactic test delivered cotrimoxazole (61.04%), mefloquine (75.23%), mefloquine /cotrimoxazole combination (89.94%) parasitamia inhibition for day 4. When compared to the individual doses of cotrimoxazole and mefloquine,the mefloquine/cotrimoxazole combo significantly (p&lt;0.05) prolonged the mean survival time in the curative,prophylactic, and suppressive tests. The combination also produced significant (p&lt;0.05) reduction in anemia characterized by increased packed cell volume, hemoglobin,red blood cells and decrease in white blood cells, neutrophils lymphocytes and monocytes when compared with single doses of cotrimoxazole and mefloquine respectively. Theresult showed that the levels of aspertate transferase,alanine alanine transferase, alkaline phosphate total protein, total bilirubin, urea, creatinine and uric acid that were slightly altered was curtailed by mefloquine/cotrimoxazole. The study showed that cotrimoxazole can be utilized as an accomplice drug with mefloquine for the management of malaria.

Effect of Carica papaya Leaf Juice on Bone Marrow Aspirate of Busulfan-induced Chronic Bone Marrow Aplasia in Mice

Introduction: Aplastic anemia is a disorder characterized by peripheral pancytopenia and hypoplastic bone marrow. Papaya, botanical name Carica Papaya, is a tropical fruit with a wide range of benefits. In past couple of years, researches have been carried out on beneficial outcomes of papaya leaf juice on blood and bone marrow, particularly platelet count. Aim: Taking into consideration the beneficial effects of papaya leaves on bone marrow, current research was done to probe the effects of C.papaya leaf juice on bone marrow differential cell count and cellularity in myelosuppressed mice where busulfan was used to induce myelosuppression. Study Design: Experimental. Place and Duration of Study: our study was performed in Post Graduate Medical Institute, Lahore in one year time. Materials &amp; Methods : It was an animal experimental study of 23 days in which 36 adult healthy swiss albino mice weighing 30-35 g of either sex were segregated into three groups with 12 mice in each group. Busulfan at a dose of 14mg/kg was given orally to the busulfan group to induce myelosuppression and to the C.papaya +busulfan group on 8 occassions (0, 3,8,11,15,18,21&amp;23) for a duration of 23 days. To observe the myeloprotective effect of Carica papaya leaf juice 10ml/kg of juice was given to the C.papaya + busulfan group daily for 23 days. After the final dose of busulfan and Carica papaya leaf juice on day 23, the samples for bone marrow aspirate were collected on same day. Results: The current study has revealed that C.papaya leaf juice not only prevented a decrease in all parameters of bone marrow aspirate but also maintained their normal values close to normal. The megakaryopoiesis was however found to be significantly higher than the normal. Keeping in view these beneficial effects carica papaya leaf juice can be used in chemotherapy induced thrombocytopenia and other related clinical conditions. Conclusion: it can be concluded from this study that C.papaya can be used in all such conditions that lead to fall in chemotherapy induced thrombocytopenia because of its property to increase megakaryopoiesis. Keywords: C.papaya, Busulfan, Megakaryopoiesis, Bone marrow failure.

Delving into The Death Signaling Pathway of Hemp Oil and Gamma Radiation in Solid Tumor Bearing Mice.

Many studies reported the diverse therapeutic potential of essential oils, including cancer prevention and treatment. Many mechanisms involved in these processes including antioxidant, antimutagenic and antiproliferative effects, or by enhancing immune function and surveillance, inducing enzymes, and enhancing detoxification, and modulating multidrug resistance. Hemp oil, obtained from Cannabis sativa L. seeds, is known for its nutritive, health-enhancing properties and bioactivity. Adult female Swiss albino mice were injected with viable Ehrlich ascites carcinoma cells (2.5 x 106 cells/mouse) then administered with hemp oil (20 mg/kg) daily for 10 consecutive days pre and post exposure to 6Gy whole body gamma radiation. Hemp oil induced a significant increase in Beclin1, VMP1, LC3, cytochrome c and Bax. Otherwise, the oil showed a significant decrease in Bcl2 and P13k either alone or in combination with ɤ-radiation. Finally this study revealed the role of hemp oil in inducing two cell death types ;autophagy and apoptosis as it may be applied as an adjuvant in cancer treatment.

Antimalarial activity of amodiaquine-moxifloxacin: A study in mice.

Background: The search for new partner drugs to increase the therapeutic activity of existing antimalarial drugs is important because of decreased Plasmodium susceptibility. Amodiaquine (AQ) is an antimalarial drug. Moxifloxacin (MX) is a fluoroquinolone antibiotic with promising antiplasmodial activity. This study evaluated the benefit of MX as a partner drug with AQ for malaria treatment in Plasmodium berghei-infected mice. Methods: Adult Swiss albino mice (28-35g) of both sexes, randomly grouped and inoculated with Plasmodium berghei were used. The mice were treated orally with AQ (10 mg/kg), MX (6 mg/kg) and AQ-MX, respectively using the curative, prophylactic and suppressive protocols. Blood samples were collected and assessed for percentage parasitemia and hematological indices. Liver samples were assessed for histological changes. Mean survival time (MST) was observed in treated mice. Results: The curative, prophylactic and suppressive tests showed that AQ-MX decreased percentage parasitemia with difference observed at p

The effects of chronic intraperitoneal monosodium glutamate in social interaction and on rotating rod in adult Swiss albino mice

Background: Short-term use of monosodium glutamate (MSG) induces anxiety in animals. Due to the lack of stringent regulations for food supplements and increase in the use of MSG in the past decade, the long-term effects of MSG need to be evaluated. There is a scarcity of the literature on the chronic effects of MSG on anxiety, hence the present study. Since anxiety models require an intact motor function, motor function was also evaluated. Aims and Objectives: The aim of the study was to evaluate the long-term effects of intraperitoneal (i.p.) MSG on mice models of anxiety (social interaction) and motor function (accelerating rota rod). Materials and Methods: The present prospective interventional study was conducted on 40 adult male Swiss albino mice. Mice were randomly divided into four equal groups to receive, distilled water, and MSG at doses of 40, 60, and 80 mg/kg/day for 3 months. Parameters were assessed at baseline, 1 month, 2 months, and 3 months of daily MSG administration. Statistical tests of significance were the Wilcoxon signed-rank test and Friedman test (within group) and Kruskal–Wallis Test (between groups), P &lt; 0.05 was considered statistically significant. Results: Social interaction time was reduced in all the MSG-treated groups (P &lt; 0.05) without any change in motor function (P &gt; 0.05). Anxiety was evident from 40 mg/kg/day MSG from the 1st month till 3 months compared to baseline and controls. Duration-dependent change in social interaction was observed with MSG at doses of 40 mg/kg/day and 60 mg/kg/day. Dose-dependent change in social interaction was not observed among treatment groups. Conclusion: Long-term administration of MSG produced anxiogenic effects at doses of 40 mg/kg, 60 mg/kg, and 80 mg/kg without impairing the motor functions in the mice.

Histopathological evaluation of ethanolic leaf extract of Lippia adoensis on the liver, kidney, and biochemical parameters in Swiss albino mice

Background: Eighty percent of Ethiopians use traditional medicine, one of which is the leaf of Lippia adoensis. Objective: The objective of this study was to investigate subacute toxicity of aqueous extract of L. adoensis leaves on the liver, kidney, and some biochemical parameters in Swiss albino mice. Subjects and Methods: LD50 was conducted with nine experimental and one control groups of adult female Swiss albino mice. In the subacute study, 40 mice of both sexes were randomly divided into four groups of ten mice per group. Group I served as control and received distilled water. Groups II–IV were used as treatment groups. They received aqueous leaf extract of L. adoensis orally at 500 mg/kg, 1000 mg/kg, and, 2000 mg/kg per body weight, respectively. SPSS version 20 statistical software was used to analyze the data. Differences at P < 0.05 were considered statistically significant. Results: In the subacute test, general signs of toxicity such as piloerection, lethargy, and convulsion were observed at 2000 mg/kg. From the 3rd week of administration, both male and female mice receiving 500 mg/kg and 2000 mg/kg and all treatment groups in the 4th week showed significant (P < 0.05) weight loss compared to control groups. Biochemical parameters under study were found to increase in all treatment groups. Several histopathological changes such as congestion, hemorrhage, severe necrosis, and infiltration of inflammatory cells in both liver and kidney in the L. adoensis-treated rats were observed at all doses of treatments. Conclusion: In the present study, the ethanolic leaf extract of L. adoensis produced dose-dependent changes such as weight loss and histopathological and biochemical changes in Swiss albino mice.

Antiplamodial effect of sulfadoxine/pyrimethamine/clindamycin: A study in parasitized mice

Triple antimalarial combination therapies may overcome the emergence of antimalarial drug resistance. Sulfadoxine/pyrimethamine (S/P) is an antimalarial drug. Clindamycin (C) has potential antiplasmodial effect. This study assessed whether the antiplasmodial activity of S/P can be augmented by C on Plasmodium berghei-infected mice. Adult Swiss albino mice (25-30g) were grouped and infected with Plasmodium berghei. The mice were orally treated daily with S/P (21.4/10.7 mg/kg), C (10mg/kg) and S/P/C, respectively using curative, prophylactic and suppressive tests. The normal and negative controls were treated daily with normal saline (0.2mL) while the positive control was orally treated with chloroquine (CQ) (10mg/kg). After treatment, blood samples were collected and evaluated for percentage parasitamia and hematological parameters. Mice were observed for mean survival time. In the curative, suppressive and prophylactic tests, S/P/C significantly decreased parasitamia levels when compared to SP or C at p&lt; 0.05. S/P/C significantly prolonged mean survival time when compared to S/P or C with difference at p&lt; 0.05. S/P, C, and S/P/C produced 65.62 %, 62. 03 % and 85.31 % parasitamia inhibitions, respectively while CQ produced 83.72 % parasitamia inhibition. S/P/C caused significant reduction in anemia marked by increased packed cell volume, hemoglobin, red blood cells and decreased white blood cells at p&lt; 0.05 when compared to SP or C. S/P/C eradicates liver merozoites and central vein congestion. C increased the antiplasmodial activity of S/P, therefore S/PC may be used for malaria treatment.

Histological changes induced by Piroxicam on the hepatic and renal tissues of mice with and without administration of Peppermint oil

Abstract Piroxicam is a popular anti-inflammatory drug that displays palliative and antipyretic activity. Peppermint oil is a common flavoring used in foods and drinks. To investigate the defensive action of Peppermint oil against the hepatic and renal histological damage induced by Piroxicam in mice. Forty healthy adult Swiss albino mice of both sexes were categorized into 4 groups (10 mice in each group): Control group (I); Treatment group (II) – injected with Piroxicam 0.3 mg/kg/rat/day via intraperitoneal route for 28 days; Treatment group (III) – oral Peppermint oil 0.2 ml/kg/day by oral gavage 24 hours preceding each injection of Piroxicam; Treatment group (IV) oral Peppermint oil alone. Blood samples were withdrawn to estimate the hepatic and renal functions. Immediately after death, specimens of liver and kidney from the four groups were isolated and put in 10% concentration buffered formalin for 24 hours then prepared for light microscopic examination. There was a highly significant rise in the serum level of hepatic enzymes (alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase and total serum bilirubin) in the group treated with Piroxicam, as compared to the control group. These returned to near normal level in the group treated with Piroxicam and Peppermint oil. Liver samples of the treated mice showed ballooning degeneration of hepatocytes, small apoptotic hepatocytes and inflammatory cellular infiltration, whereas kidney sections revealed cystic dilatation of Bowman’s space, shrinkage of glomerular tuft and apoptosis of epithelial cells lining the tubules. In contrast, the addition of peppermint oil efficiently ameliorated the hepatic and renal tissue changes. Piroxicam induces hepatorenal toxicity as exhibited by histological, histochemical and biochemical findings. Peppermint oil shows ameliorative properties against the hepatorenal toxic effects induced by Piroxicam.

Pharmacological evaluation of antinociceptive and anti-inflammatory activities of LQFM202: a new piperazine derivative.

Advances have been made in the search for new multi-target modulators to control pain and inflammation. Therefore, compound 3,5-di-tert-butyl-4-hydroxyphenyl)(4-methylpiperazin-1-yl)methanone (LQFM202) was synthesised and evaluated. First, in vitro assays were performed for COX-1, COX-2, and 5-LOX enzymes. Subsequently, adult female Swiss albino mice treated orally with LQFM202 at doses of 25-200mg/kg were subjected to acetic acid-induced writhing, formalin-induced pain, carrageenan-induced hyperalgesia, carrageenan- or zymosan-induced paw oedema, or pleurisy. LQFM202 inhibited COX-1, COX-2, and LOX-5 (IC50 = 3499µM, 1565µM, and 1343µM, respectively). In acute animal models, LQFM202 (50, 100, or 200mg/kg) decreased the amount of abdominal writhing (29%, 52% and 48%, respectively). Pain in the second phase of the formalin test was reduced by 46% with intermediate dose. LQFM202 (100mg/kg) reduced the difference in nociceptive threshold in all 4h evaluated (46%, 37%, 30%, and 26%, respectively). LQFM202 (50mg/kg) decreased the carrageenan-oedema from the second hour (27%, 31% and 25%, respectively); however, LQFM202 (100mg/kg) decreased the carrageenan-oedema in all hours evaluated (35%, 42%, 48% and 50%, respectively). When using zymosan, LQFM202 (50mg/kg) decreased the oedema in all hours evaluated (33%, 32%, 31% and 20%, respectively). In the carrageenan-pleurisy test, LQFM202 (50mg/kg) reduced significantly the number of polymorphonuclear cells (34%), the myeloperoxidase activity (53%), TNF-α levels (47%), and IL-1β levels (58.8%). When using zymosan, LQFM202 (50mg/kg) reduced the number of polymorphonuclear and mononuclear cells (54% and 79%, respectively); and the myeloperoxidase activity (46%). These results suggest antinociceptive and anti-inflammatory effects of LQFM202.

Preclinical Safety Assessment of Chemically Cross-Linked Modified Mandua Starch: Acute and Sub-Acute Oral Toxicity Studies in Swiss Albino Mice.

In the present era, 28 days of repeated-dose-toxicity study following the Organization for Economic Cooperation and Development (OECD) guidelines 407 is compulsory for every drug to go through phase 1 clinical trials. The increasing demand for high-resistant starch containing nutraceuticals and the applicability of modified starch in development of targeted drug delivery inspired us to investigate the toxic profile of mandua starch chemically cross-linked by epichlorohydrin and compare it with alkali-isolated starch in healthy adult Swiss albino mice, which can be the first step for exploring the use of epichlorohydrin-cross-linked mandua starch (ECC-MS) as a pharmaceutical excipient. Histopathological examinations of the kidney and liver did not expose noteworthy abnormalities in the treated mice. There were no clinical and mortality symptoms of toxicity observed during the repeated-dose-toxicity study. The oral consumption of ECC-MS did not pose any harm as it was neither lethal nor had any harmful hematological, biochemical, psychological, anatomical, and behavioral effects. The use of ECC-MS and alkali-isolated mandua starch (AMS) was found safe at a dose of 2000 mg/kg body weight in the acute toxicity study and at doses of 2000, 1500, and 1000 mg/kg body weight in the sub-acute toxicity study as no detrimental effects were observed after oral administration in mice for 14 and 28 days, respectively.

Histopathological Evaluation of Ethanolic Leaf Extract of Lippia adoensis on Liver, Kidney, and Biochemical Parameters in Swiss Albino Mice.

BackgroundEighty percent of Ethiopians use traditional medicine, one of which is the leaf of Lippea adoensis.ObjectiveTo investigate subacute toxicity of aqueous extracts of L. adoensis leaves on the liver and kidney and biochemical parameters in Swiss albino mice.MethodsLD50 was assessed with nine experimental groups and one control group of adult female Swiss albino mice (five in each group). In the subacute study, 40 mice of both sexes were randomly divided into four groups of ten mice (both sexes) per group. Group I served as controls and received distilled water and feed only. Groups II–IV were used as treatment groups. They received calculated doses of aqueous leaf extracts orally at doses of 500 mg/kg, 1000 mg/kg, and 2000 mg/kg body weight, respectively.ResultsSince 80% of deaths occurred at the 10,000 mg/kg body-weight dose in this experiment, LD50 was considered to be <10,000 mg/kg. In the subacute test, general signs of toxicity like hypoactivity, piloerection, lethargy, and a single episode of convulsion were observed at the 2000 mg/kg dose. Beginning from the third week of administration, both male and female mice receiving 500 mg/kg and 2000 mg/kg and all treatment groups in the fourth week showed significant (P<0.05) weight loss compared to controls. Biochemical parameters were found to increase in all groups treated with ethanolic leaf extracts. Several histopathological changes like congestion, hemorrhage, severe necrosis, and infiltration of inflammatory cells in both liver and kidney in the L. adoensis–treated rats were observed at all doses.ConclusionIn the present study, the ethanolic leaf extracts of L. adoensis produced dose-dependent weight loss and histopathological and biochemical changes in Swiss albino mice.

Changes in CD and Correlation with Hepatic Insulin Resistance Index and Triacylglycerol 36 Level in Liver of Malarial Infected Mice Treated with Phyllanthus amarus

Phyllanthus amarus is an herb for the treatment of various ailments including malaria. Its antiplasmodial properties and antioxidant capacity have been reported, but very little is known about its effect on CD36 in relation to hepatic insulin resistance and triacylglycerol level. Hence, this study was undertaken to evaluate the changes in soluble CD36 concentrations and correlation with hepatic insulin resistance index and triacylglycerol levels in liver of Plasmodium berghei malarial parasite infected mice treated with graded doses of Phyllanthus amarus ethanolic leaf extract. Thirty (30) adult Swiss albino mice of both sexes weighing between 20-30g were assigned into six (6) groups (n=5/grp). Crude ethanolic leaf extract of Phyllanthus amarus was administered at 150, 300 and 450mg/kg/d as single daily dose for 7 days. On the 8th day of study, the mice were sacrificed under chloroform anaesthesia after an overnight fast. Blood sample was collected by cardiac puncture and centrifuged to obtain serum which was used for the assay of serum CD36, glucose and insulin, while, liver of each mouse was excised and processed for the assay of varying doses (150, 300 and 450mg/kg/d) of Phyllanthus amarus crude ethanolic leaf extract to experimental mice infected with P. berghei malarial parasite for seven days maintained serum soluble CD36 (3.40±0.52pg/ml, 3.47±0.46pg/ml and 3.37±0.46pg/ml), hepatic insulin resistance index (0.85±0.10, 0.77±0.17 and 0.82±0.13) and liver triacylglycerol (134.33±15.95mg/dl, 174.00±11.27mg/dl and 163.67±11.02mg/dl) levels, respectively, in trends that compared well with the Control and chloroquine – treated data ( C D 3 6 = 3.03±0.12pg/ml, liver TAG = 139.33±12.01, HIR index = 0.64±0.07). Correlation of CD36 with liver triacylglycerol for the malarial infected group without treatment was strongly positive, while, that with hepatic insulin resistance index was strongly negative. The control and chloroquine treated groups produced similar correlation pattern, but those for the extract-treated were weaker. Malarial infection in experimental mice significantly (p&lt;0.05) increased serum soluble CD36 and this impacted HIR index and liver TAG. However, extract and chloroquine treatments ameliorated the malaria-induced level of serum soluble CD36 and hepatic triacylglycerol, using documented methods. Results indicate that infection of mice with Plasmodium berghei malarial parasite yielded significant increase in level of CD36 (5.40±0.70pg/ml) and liver triacylglycerol, TAG (259.00±7.21mg/dl), but abnormal reduced (p&lt;0.05) hepatic insulin resistance, HIR index (0.37±0.05) when compared with the control mice (CD36 = 3.47±0.46pg/ml, liver TAG = 161.00±10.00, HIR index = 0.68±0.18) at the 5% probability level. However, administration of as starting materials for drugs (Sofowora, 1993). Plants have provided an alternative strategy in research for new drugs. It is likely that plants will continue to be a valuable source of new molecules which may after possible chemical manipulations provide new and improved drugs (Shan et al., 2006). One of such plants is Phyllanthus amarus.Phyllanthus amarus belongs to the family Euphorbiaceae (the spurge family) from which the largest genus is the Euphorbia. It has about eight hundred (800) species which are found in tropical and subtropical countries of the world (Mazumder et al., 2005). Phytochemicals identified in the leaf extract include alkaloids, flavonoids, tannins, saponins, anthraquinone and glycosides (Onyesom et al., 2015). The antimalarial activity of P. amarus has been observed (Onyesom and Adu, 2015). Malaria is a mosquito borne infectious disease of humans caused by eukaryotic protists of the genus Plasmodium. It is widespread in tropical and subtropical regions of the world including much of the sub-Saharan Africa. In Nigeria, malaria is mostly caused by Plasmodium falciparum. The association with HIR index and liver TAG in manners that were similar to the control trend.

Preliminary phytochemical and analgesic activity extract of Kigelia pinnata leaf

Kigelia pinnata Linn. (Balam Kheera) belongs to the family of Bignoniaceae and is commonly called the "sausage" tree because of its hugs fruits. The present research was conducted to investigate the analgesic activity of different extracts of leaves of Kigelia pinnata. Preliminary phytochemical investigations were performed by chemical tests. In the preliminary phytochemical test, the leaves extract showed the presence of phytosterols, alkaloids, glycosides, flavonoids, saponins, tannins, and phenolic compounds. An acute toxicity study was performed according to OECD guidelines. The analgesic activity was conducted by Hot Plate Method and Tail Immersion Test on adult Swiss albino mice. In Acute Toxicity Study, oral administration of extract was found safe at a dose of 2,000 mg/kg, p.o. and produced no signs of toxicity. The methanolic extract was found to be significant in Analgesic activity.

Methanol leaf extract of Paullinia pinnata exerts sleep-enhancing and anticonvulsant effects via a mechanism involving the GABAergic pathway

PurposeLeaf extracts of Paullinia pinnata L. (Sapindaceae) are used in ethnomedicine for the treatment of central nervous system-related diseases such as insomnia and epilepsy. We determined the bioactive constituents, sleep-enhancing and anti-convulsant potentials, and possible mechanisms of action of P. pinnata methanol leaf extract (PPME). MethodsGas Chromatography-Mass spectrometry (GC-MS) was used to identify the bioactive compounds in PPME. Adult Swiss albino mice were used. Oral LD50 was estimated before administering PPME at oral doses of 100, 200, and 400 mg/kg to test for sleep-enhancing and anticonvulsant properties. To evaluate the possible mechanisms involved, mice were pretreated for five days with isoniazid (NIH) a GABA synthesis inhibitor before re-evaluation of sleep-enhancing property. The activities of glutamic acid decarboxylase (GAD), superoxide dismutase (SOD), catalase (CAT), and the level of malondialdehyde (MAD) in the brain of mice were also evaluated after a 7-day treatment with the extract. ResultsTwenty-five phytochemical compounds were identified from GC-MS analysis with fatty acid esters of lauric and fumaric acids being the most abundant. The oral LD50 of PPME was estimated to be greater than 5000 mg/kg. Doses of PPME significantly (p < 0.001) reduced sleep latency and increased the duration of sleep of phenobarbital-treated mice. Except for 100 mg/kg, the doses also significantly protected mice against maximum electroshock (p < 0.001) and pentylenetetrazole (p < 0.05) but not strychnine-induced convulsions. Pretreatment with isoniazid (INH) almost completely reversed the sleep-enhancing effects of PPME. The activities of GAD, SOD, and CAT, and level of MDA in brains of the mice were significantly (p < 0.001) increased by doses of PPME administered for five days. ConclusionThe extract possesses sleep-enhancing and anticonvulsant properties which depend on increased level of GABA in the brain. Its antioxidant action may be neuroprotective against free radicals-induced damage.