Histopathological Studies Of Liver Research Articles

The ameliorating effect of Rutin on hepatotoxicity and inflammation induced by the daily administration of vortioxetine in rats

BackgroundVortioxetine (VORTX) is a potent and selective type of selective serotonin reuptake inhibitor (SSRI) that is mainly prescribed for treating major depression along with mood disorders as the first drug of choice. Limited previous findings have indicated evidence of liver injury and hepatotoxicity associated with daily VORTX treatment. Rutin (RUT), which is known for its antioxidant properties, has demonstrated several beneficial health actions, including hepatoprotection. Therefore the current study aimed to evaluate and assess the ameliorative effect of RUT against the hepatotoxic actions of daily low and high-dose VORTX administration.MethodsThe experimental design included six groups of rats, each divided equally. Control, rats exposed to RUT (25 mg/kg), rats exposed to VORTX (28 mg/kg), rats exposed to VORTX (28 mg/kg) + RUT (25 mg/kg), rats exposed to VORTX (80 mg/kg), and rats exposed to VORTX (80 mg/kg) + RUT (25 mg/kg). After 30 days from the daily exposure period, assessments were conducted for serum liver enzyme activities, hepatotoxicity biomarkers, liver antioxidant endogenous enzymes, DNA fragmentation, and histopathological studies of liver tissue.ResultsInterestingly, the risk of liver damage and hepatotoxicity related to VORTX was attenuated by the daily co-administration of RUT. Significant improvements were observed among all detected liver functions, oxidative stress, and inflammatory biomarkers including aspartate aminotransferase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), albumin, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), glutathione S-transferase (GST), total protein, acid phosphatase, N-Acetyl-/β-glucosaminidase (β-NAG), β-Galactosidase (β-Gal), alpha-fetoprotein (AFP), caspase 3, and cytochrom-C along with histopathological studies, compared to the control and sole RUT group.ConclusionThus, RUT can be considered a potential and effective complementary therapy in preventing hepatotoxicity and liver injury induced by the daily or prolonged administration of VORTX.

Development of oral formulation of Lepidium seeds significantly decreases the high blood glucose levels in diabetic rats: in vitro formulation and in vivo antidiabetic performance

Background Lepidium sativum, Garden Cress (GC), seeds have a lot of natural molecules with a pronounced activity against different disorders. It was reported that GC seeds have the ability to lower the blood glucose level. Aim The aim of this work was to formulate GC seeds into oral tablets containing a fixed dose of the grounded seeds. Furthermore, the anti-diabetic performance of the prepared tablets was studied in the streptozotocin rats’ model in comparison with positive control metformin. Methods Micrometrics of GC grounded seeds with different excipients were investigated. Then, GC tablets were prepared via direct compression technique. GC tablets were characterized for their uniformity of dosage unit, friability, hardness, disintegration time, and in vitro release. The antidiabetic effect was studied in rats for a period of 28 days. Glycosylated hemoglobin, liver performance, and lipid levels include total cholesterol (TC), triglycerides (TGs), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were also estimated. In addition, histopathological study of liver and pancreas was also performed. Results Prosolv®EasyTab produced tablets with higher hardness, lower disintegration time, and fast release. GC tablets significantly lower the elevated blood glucose level. In addition, they have antihyperlipidemic activity, hepatocellular protective role and restore the histology of the liver and pancreas. Conclusion GC tablets could be a promising alternative formulation to control the high blood glucose level in diabetic rats rather than chemically derivatized drugs.

Liver proteomic analysis of Bai-Hu-Tang treatment to systemic inflammatory response

IntroductionBai-Hu-Tang (BHT), a classical prescription of traditional Chinese medicine, has been extensively used to treat many infectious diseases and high fever syndrome. However, the specific mechanisms and molecular targets affected by BHT have not been thoroughly investigated in the context of treating systemic inflammatory response. This study aimed to explore the comprehensive protein mechanism of BHT during treatment of the lipopolysaccharide (LPS) systemic inflammatory response. MethodsThe rabbit model of the systemic inflammatory response was established by LPS intravenous injection (15 μg/kg·bw), and aqueous extract of BHT was administrated by gavage to the model rabbits. At the same time, a group of normal rabbits were also gavaged with BHT alone. Based on liver histopathological study, total liver protein was extracted, and two-dimensional liquid chromatography (LC) - tandem mass spectrometry (MS) coupled with isobaric tags for relative and absolute quantification (iTRAQ) labeling analysis was employed to identify and quantify the liver proteome. Differentially expressed proteins (DEPs) were screened through comparing with control animals, and bioinformatics analysis was conducted to explore kyoto encyclopedia of genes and genomes (KEGG) pathways enrichment and protein clustering among different groups. Real time polymerase chain reaction (RT-PCR) was used to detect the mRNA expression levels of 4 ribosomal proteins to verify the proteomic results. ResultsThe results showed that ribosome biogenesis is the most significant biological process and ribosomal DEPs mainly distribute in the large subunit of ribosome during the BHT treatment to the LPS systemic inflammatory response. RT-PCR confirmed that BHT had an effect on mRNA expression of ribosome proteins. DiscussionTherefore, the biological pathway of ribosome biogenesis and the regulation of ribosomal proteins may be the cruicial factors when employing BHT for the treatment of the systemic inflammatory response induced by LPS.

A Prospective Observational Study on the Role of Special Stains in Physiological and Histopathological Study of Liver

A Prospective Observational Study on the Role of Special Stains in Physiological and Histopathological Study of Liver

Ameliorative effects of berberine and selenium against paracetamol-induced hepatic toxicity in rats.

Paracetamol (PCM) overdosing induces hepatotoxicity, which can result in death if the dose is high enough and the patients are not given N-acetyl cysteine. Berberine (BBR) has a variety of biological proprieties including anti-inflammatory and antioxidant activities. Assessment of the potential effect of BBR and selenium when used alone or together on the PCM-induced acute hepatic toxicity in rats. This research involved 40 clinically healthy mature adult male albino rats, their weights ranged from 150 to 200 g and housed in standard conditions. Our study involved evaluating the potential effect of BBR and selenium when used alone or together on the PCM-induced acute hepatic toxicity via estimation of the liver function tests, determination of the antioxidant enzyme activities, lipid peroxidation markers, immune-modulatory effects, liver histopathological, and immunohistochemical studies. Co-treatment of BBR (150 mg/kg BW) with selenium (5 mg/kg BW) showed significant improvement in the liver function parameters, the antioxidant enzyme activities, reduction in the nitric oxide (NO), lysozyme, malondialdehyde (MDA), TNF-α, and TGF-β1 levels, and marked elevation in the IgM levels. Altogether, BBR, selenium, or both augment antioxidant activity and alleviate PCM-induced hepatic toxicity.

Hepatoprotective and anti-hyperglycemic effects of ferulic acid in arsenic-exposed mice.

Arsenic is a toxic metalloid that increases the risk of hepatotoxicity and hyperglycemia. The objective of the present study was to assess the effect of ferulic acid (FA) in mitigating glucose intolerance and hepatotoxicity caused by sodium arsenite (SA). A total of six groups including control, FA 100mg/kg, SA 10mg/kg, and groups that received different doses of FA (10, 30, and 100mg/kg), respectively just before SA (10mg/kg) for 28 days were examined. Fasting blood sugar (FBS) and glucose tolerance tests were conducted on the 29th day. On day 30, mice were sacrificed and blood and tissues (liver and pancreas) were collected for further investigations. FA reduced FBS and improved glucose intolerance. Liver function and histopathological studies confirmed that FA preserved the structure of the liver in groups received SA. Furthermore, FA increased antioxidant defense and decreased lipid peroxidation and tumor necrosis factor-alpha level in SA-treated mice. FA, at the doses of 30 and 100mg/kg, prevented the decrease in the expression of PPAR-γ and GLUT2 proteins in the liver of mice exposed to SA. In conclusion, FA prevented SA-induced glucose intolerance and hepatotoxicity by reducing oxidative stress, inflammation, and hepatic overexpression of PPAR-γ and GLUT2 proteins.

Acute exposure of Cr and Cu induces oxidative stress, genotoxicity and histopathological alterations in snakehead fish Channa punctatus

Aim: This study aimed to investigate the oxidative stress, genotoxicity and histopathology after sub-lethal exposure of chromium (Cr6+) and copper (Cu+2) to common food fish Channa punctatus. Metal exposure to fishes of River Ganga is a very common phenomenon due to their ubiquitous nature and through discharge of domestic and industrial waste into the river water. Methodology: An in-vitro experiment was performed to study ill effects of metallic stressors on fish. Fishes were divided into seven groups. Group I served as control, Group II, III, IV as 1/20th ,1/10th and 1/5th of 96 hr-LC50 of Cr6+. Group V, VI and VII were similarly treated with Cu at 1/20th, 1/10th and 1/5th of 96 hr LC50 of Cu+2, respectively. All the treatments were done for 15, 30 and 45 days of exposure period. Genotoxicity was evaluated by micronuclei (MN) induction. Enzymatic and non-enzymatic oxidative stress markers, including reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione reductase (GR), and glutathione peroxidase (GPx) were evaluated. Histopathological studies of liver and kidney tissue were also performed. Results: Stress biomarkers were more profound in fishes of chromium treated groups in comparison to copper. Particularly, SOD and CAT showed a significant hike in the activity levels. ROS levels in blood cells increased significantly (p < 0.05) in all the treated groups (Group II, III, and IV) in a dose dependent manner as compared with control (Group I). There was significant induction in micronuclei (MN) frequency in all the treated groups for both the metals. The highest frequency of MN induction was recorded in Group IV after 96 hr of the exposure period.Significant histological alterations were observed in liver and kidney of treated fish, changes were more pronounced in chromium treated fish than copper. Interpretation: Acute exposure of chromium and copper induces ROS and generates oxidative stress mediated genotoxicity and histopathological perturbations in the prime organs of fish.Cr and Cu induces the changes in the production and accumulation of enzymatic antioxidant system for the regulation and scavenging of ROS induced by Cr and Cu. Key words: Channa punctatus, Genotoxicity, Histology, Heavy metals, Micronuclei, Oxidative stress

The Hepatotoxicity of Nigella sativa Oil Linked to the Route of Administration

Background: Even Nigella sativa oil (NSO) has several pharmacological effects; the route of administration is critical to obtain the desired activity in which intraperitoneal injection (IP) of oil recruits macrophages and induces inflammation. Objective: The current study aimed to determine the best administration route of NSO in rats either oral or IP. Methods: The components of NSO, routine blood analyses, hepatic oxidative stress and proinflammatory parameters, and liver histopathological study were evaluated. Results: NSO contained 32.14% E,E,Z- 1, 3 , 12- nonadecatriene- 5, 14 diol, 25% thymoquinone (TQ) and 3.74% dimethyl sulfoxide (DMSO). In addition, the rats who received IP injection of NSO showed an increase in hepatic enzymes, lipid profiles, oxidative stress, and inflammatory markers. This was associated with hepatic up-regulation of the A disintegrin and metalloproteinase 17 (ADAM- 17) genes, which are corroborated by a reduction in hepatic tissue inhibitor of metalloproteinase 3 (TIMP-3) concentration. These indications were seen in rats given a small amount of DMSO (NSO vehicle), indicating that NSO-oral delivery was safer than IP. Conclusion: NSO-IP administration promotes the hepatic oxidative stress-inflammation axis; thus, NSO is a generally safe chemical, especially when administered orally to experimental animals.

Evaluation of Antidiabetic Activity of Oxadiazole Derivative in Rats.

The oxadiazole ring has long been used for the treatment of several diseases. This study aimed to analyze the antihyperglycemic and antioxidant roles of the 1,3,4-oxadiazole derivative with its toxicity. Diabetes was induced through intraperitoneal administration of alloxan monohydrate at 150 mg/kg in rats. Glimepiride and acarbose were used as standards. Rats were divided into groups of normal control, disease control, standard, and diabetic rats (treated with 5, 10, and 15 mg/kg of 1,3,4-oxadiazole derivative). After 14 days of oral administration of 1,3,4-oxadiazole derivatives (5, 10, and 15 mg/kg) to the diabetic group, the blood glucose level, body weight, glycated hemoglobin (HbA1c), insulin level, antioxidant effect, and histopathology of the pancreas were performed. The toxicity was measured by estimating liver enzyme, renal function, lipid profile, antioxidative effect, and liver and kidney histopathological study. The blood glucose and body weight were measured before and after treatment. Alloxan significantly increased blood glucose levels, HbA1c, alanine transaminase, aspartate aminotransferase, urea, cholesterol, triglycerides, and creatinine. In contrast, body weight, insulin level, and antioxidant factors were reduced compared to the normal control group. Treatment with oxadiazole derivatives showed a significant reduction in blood glucose levels, HbA1c, alanine transaminase, aspartate aminotransferase, urea, cholesterol, triglycerides, and creatinine as compared to the disease control group. The 1,3,4-oxadiazole derivative significantly improved body weight, insulin level, and antioxidant factors compared to the disease control group. In conclusion, the oxadiazole derivative showed potential antidiabetic activity and indicated its potential as a therapeutic.

Hepatocorrective effects of Hydroethanolic Extract of Cocos nucifera L. sprout and Borassus flabellifer Sprout in Carbon tetrachloride (CCl4) induced hepatotoxic rats

The objective of the study was to determine the hepatocorrective activity of hydroethanolic extract of Cocos nucifera L. and Borassus flabellifer sprout in carbon tetrachloride (CCl4) induced hepatotoxic rats. The qualitative phytochemical analysis was used to evaluate the secondary metabolites like flavonoids, saponins, proteins in the hydroethanolic extract of Cocos nucifera L. sprout and Borassus flabellifer sprout which also reveals the presence of pharmacologically active phytochemicals. The toxicant CCl4 was used to induce hepatotoxicity in 1 : 1 mixture with olive oil. Hydroethanolic extract of Cocos nucifera L. sprout and Borassus flabellifer sprout were administrated in the doses of 100mg/kg and 200mg/kg body weight orally for 21 days. Silymarin was used as a standard drug. The hepatocorrective effect of the extracts were evaluated by the assessment of biochemical parameters and liver markers such as Aspartate transaminase (AST), Alanine transaminase (ALT), Alkaline phosphatase (ALP), Gamma glutamyl transferase (GGT), Lactate dehydrogenase (LDH), and also by the assessment of Total protein, Creatinine, Urea, Total cholesterol, Lipid peroxidation (LPO), Vitamin C, Superoxide dismutase (SOD), Catalase, Prothrombin Time (PT), Glutathione peroxidase (GPx), Reduced glutathione (GSH) etc. Assessment of enzymatic and nonenzymatic antioxidants and histopathological studies of liver were also done for the hepatocorrective activity determination. Treatment of rats with hydroethanolic extract of Cocos nucifera L. and Borassus flabellifer sprout significantly reduced the liver damage and the symptoms of liver injury by restoration of architecture of liver. The overall findings suggest that both sprouts have potent hepatocorrective activity in carbon tetrachloride induced hepatotoxic rats.

Ameliorating Effects of Croton Bonplandianus Leaves against Gentamicin Induced Acute Liver and Kidney Injury: A Biochemical and Histopathological Investigation

The utilization of natural constituents for the treatment of various medical complaints is well established. The members of the Euphorbiaceae family, especially the Croton genus, are reported to be rich in diterpenoids and showing various biological activities. Many activities of Croton bonplandianus are still unfolded therefore, current study is designed to evaluate the ameliorative effects of aqueous extract of C. bonplandianus against gentamicin-induced liver and kidney injuries in rats. The aqueous extract of leaves (27-81 mg/kg) was administered to albino rats Wistar strain for eight days with concurrent administration of gentamicin (100 mg/kg) daily. The protective effect of the aqueous extracts on the liver was determined by liver function tests (SGPT, ALT, GGT, Bilirubin) and kidney functions were evaluated by assessment of plasma biomarkers including urea, creatinine, uric acid and electrolytes (sodium, potassium, chloride and bicarbonate). Histopathological studies of liver and kidney tissue were carried out by Hematoxylin and Eosin (H& E) staining confirmation of the consequences. Significant alterations in liver and kidney tissues treated groups with aqueous extracts of leaves were obtained in lower doses (27-54 mg/kg). Similarly, serum levels of SGPT, ALT, GGT, bilirubin, creatinine, and urea in the treated group were significantly reduced (P < 0.01) at similar doses, whereas no significant changes were founded in levels of ions and uric acids. The histological examination of the liver and kidney confirmed the biochemical changes in treated rats. The underlying results demonstrate the protective effect of aqueous leave extracts Croton bonplandianus on an acute liver and kidney injury rat model. The hepato and renal protective effects of C. bonplandianus are certainly due to the presence of diterpenoids flavonoids and polyphenols exhibiting free radical or oxygen scavenging activities. Keywords: Croton bonplandianus , gentamicin, histopathological studies, nephroprotective effect. https://doi.org/10.55463/issn.1674-2974.50.3.15

Solanum anomalum Leaf Extract and Fractions Attenuate Oxidative Stress and Liver Injuries in Alloxan-Induced Diabetic Rats

The leaf of Solanum anomalum used in ethnomedicine for the treatment of various ailments such as diabetes was evaluated for antioxidative stress and hepatoprotective potentials against hepatic injuries in alloxan-induced diabetic rats. Antioxidative stress and hepatoprotective activities of leaf extract and fractions (70-210 mg/kg) were assessed by determining oxidative stress markers levels, liver function indices and histopathological study of livers of treated rats. The leaf extract and fractions caused significant (p<0.05 – 0.001) increases in the levels of oxidative stress markers (SOD, CAT, GPx, GSH) in the livers of the treated diabetic rats. The extract/fractions treatment caused reduction in liver enzymes (ALT, AST and ALP), total and direct bilirubin. Histology of the livers revealed absence or significant reductions in pathological features in the treated diabetic rats compared to untreated diabetic rats. The results show that the leaf extract and fractions of S. anomalum has antioxidative stress and hepatoprotective potentials which may be due to the antioxidant activities of their phytochemical constituents.

Antagonistic Effect of Dichloromethane on Oreochromis mossambicus and Immune Stimulation Activity of Aloe Vera

This study examined the aquatic toxicity of dichloromethane (DCM) on Oreochromis mossambicus. Along with aquatic toxicity studies, in silico research was also conducted to identify ways of improving the fish’s immune system, which may help to fight the oxidative stress and neurotoxic effects of DCM. The activities of glutathione S-transferase and acetylcholinesterase enzymes were studied in samples from the brains, muscles, livers, and gills of fish treated with different concentrations of DCM (730, 760, and 790 ppm). Histopathological and hematological studies were also completed at various concentrations of DCM. Molecular docking studies of the bioactive compounds of Aloe vera against interleukin-1β (IL-1β) were conducted, and drug properties were also analyzed. The lethal concentration (LC50) of DCM in the fish was found to be 760 ppm. The hematological study revealed that tissues exposed to 760 ppm of DCM had an elevated leukocyte count, high amounts of hemoglobin, and very low platelet counts. The liver histopathological study identified cellular alterations such as necrosis, and the gills showed lamellar fusion and congestion. The compound sitosterol showed strong binding energy (-12.398 kcal/mol) against IL-1β, followed by squalene (−12.157 kcal/mol). Pharmacokinetic properties were also analyzed, with satisfactory results. Thus, the hematological and histopathological studies reveal that DCM has a potential ability to induce oxidative stress and neurotoxic effects. Hence, the phytochemicals of Aloe vera can improve the immune system to fight against the neurotoxicity of DCM, which can be further validated by in vitro and in vivo studies.

Nanogold morphologies with the same surface chemistry provoke a different innate immune response: An in-vitro and in-vivo study

Gold nanomaterials (GNMs) have unique optical properties with less antigenicity, and their physicochemical properties have strong relation with an immunological response at bio-interface including antigenicity. An interpretation of this correlation would significantly impact on the clinical and theranostic applications of GNMs. Herein, we studied the effect of GNMs morphology on the cytotoxicity (in-vitro), innate immune responses, hepatotoxicity, and nephrotoxicity (in-vivo studies) using gold nano-cups (GNCs), porous gold nanospheres (PGNSs) and solid gold nano particles (SGNPs) coated with the same ligand to ensure similar surface chemistry. The cytotoxicity was assessed via sulfo-rhodamine B (SRB) assay, and the cytotoxicity data showed that morphological features at nanoscale dimensions like surface roughness and hollowness etc. have a significant impact on cellular viability. The biochemical and histopathological study of liver and kidney tissues also showed that all GNMs did not show any toxicity even at high concentration (100 μL). The relative quantification of cytokine gene expression of TNF-α, IFN-γ, IL-4, 1L-6, and 1L-17 (against each morphology) was checked after in-vivo activation in mice. Among the different nanogold morphologies, PVP stabilized GNCs (PVP-GNCs) showed the highest release of pro-inflammatory cytokines, which might be due to their high surface energy and large surface area for exposure as compared to other nanogold morphologies studied. The pro-inflammatory cytokine release could be suppressed by coating with some anti-inflammatory polymer, i.e., inulin. The in-vitro results of pro-inflammatory (TNF-α, IL-1) cytokines also suggested that all GNMs may induce activation of macrophages and Th1 immune response. The in-vivo activation results showed a decrease in mRNA expression of the cytokines (TNF-α, IFN-γ, IL-4, 1L-6 and 1L-17). Based on these findings, we proposed that the shape and morphology of GNMs control their immune response at nano-bio interface, and it must be considered while designing their role for different biomedical applications like immuno-stimulation and bio-imaging.

Study the Effects of Anadrol Overdose on Liver Function in Male Rats

Anadrol (oxymetholone) is an active androgenic anabolic steroid that has been clinically studied in numerous diseases since the 1960s. It is used in the treatment of anemia and the replacement of male sex steroids. Unfortunately, in attempts to improve physical performance, Anadrol could be misused by athletes, that can lead to poisoning contributes to hepatotoxicity. The aim of this study was to investigate the impact of anadrol on the liver function in rat model, via assessment of liver enzymes and histopathological study. A forty male rats, weights about (200-300 gm), aged 8-12 weeks, after acclimatization, the rats were ‎randomly divided into four groups (10 rats in each group) as follow: control group (in which all rats were administered normal saline (NS) via oral gavage), anadrol 10 mg/kg (Iran-Tehran Company) group (in which all rats were administered anadrol 10mg/kg via oral gavage), anadrol 20 mg/kg group (in which all rats were administered anadrol 20mg/kg via oral gavage), and anadrol 30 mg/kg group (in which all rats were administered anadrol 30mg/kg via oral gavage), the oral administration had continued for 8 weeks in single daily dose regimen. At the end of study liver function enzymes such as alanine aminotransferase & aspartate aminotransferase were measured via chemical analysis. Then histopathological study was done on the liver tissue in the four experimental groups. Male rats that treated with anadrol displayed high level of liver enzymes, including as alanine aminotransferase & aspartate aminotransferase, as compared with control group. On the other hand, histopathological study exhibited significant injurious changes in the hepatic tissue in anadrol groups comparing with control. When anadrol given in high doses results in hepatic injury, that can be cleared via elevated levels of hepatic enzymes and liver histopathological changes.

IDF21-0138 Antidiabetic and anti-radical effects of Garcinia kola seeds in dexamethasone-induced-hyperglycemic rats

Background: Seeds of Garcinia kola are consumed as stimulant due to its bitter and astringent taste. In traditional medicine, the maceration of seeds or roots are used to treat various diseases including liver diseases, cough, diabetes and complications. Several studies have been conducted to validate or not the empirical use of G. kola. Aim: Here using in vivo model we assessed some pharmacological properties of the hydroalcoholic extract of G. kola in dexamethasone-induced-hyperglycemic rat, hypoglycemia, anti-hyperglycemia, spasmolytic and laxative activities, then in vitro model to assess antiradical activity. Method: The decoction of the hydroalcoholic extract of G. kola seeds was obtained by introducing 250 g of powder into an Erlen Mayer by supplementing the total volume to 1L with water-ethanol mixture (30:70), then brought to boil at 80°C for 15 min. After cooling and filtration with Watman paper No. 4, the filtrate was concentrated with rotavapor. The extract was reconstituted in a 100% DMSO solution for purification and then prepared at 1% at concentrations of 0.5mg/mL and 1mg/mL for administration to animals at doses of 50 and 100 mg/kg. To evaluate antidiabetic properties, 30 rats of Wistar strain were used. The animals were divided into 5 groups of 6 rats each. Hyperglycemia was induced by a single intravenous injection of 4 mg/kg of dexamethasone for 3 days. Animals with glycemia no more than 120 mg/dL after 12 h fasting were considered as hyperglycemic then used for experiments. Glibenclamide® 2.5 mg/kg was used as a positive control. To evaluate the effect of G. kola on intestinal transit in normo-glycemic and hyperglycemic rat, we used 30 rats. Each group consisted of 3 normo-glycemic rats and 3 hyperglycemic rats. Imodium® and Fructin® were used as positive controls respectively for the evaluation of the spasmolytic and laxative effect of G. kola. Anti-radical activity of G. kola was assessed in vitro by inhibition of the activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH). Results: At doses 50 and 100 mg/kg G. kola significantly (P<0.001) regulate dexamethasone induced hyperglycemia after from a week treatment compared to the control normo-glycemic and hyperglycemic. The extract at both doses significantly (P<0.001) inhibited the spasmolytic activity in both normo-glycemic and hyperglycemic rats compared to Imodium®. In rats made hyperglycemic, only dose 100 mg/kg significantly (P<0.05) increase laxative effects when compared to the negative control. The potentiation of this effect was dose-related because no significant difference (P>0.05) was observed in both normo-glycemic and hyperglycemic rats in comparison to the reference laxative drug (Fructin®). In vitro anti-radical activity of G. kola revealed vitamin C-like anti-radical activity. Indeed, it appears from the histopathological study of liver, kidney and pancreas that extract restored the histological integrity of these organs initially altered by dexamethasone. Discussion: These pharmacological effects of G. kola could be attributed to numerous flavonoids, as plant extract revealed a total flavonoid 2.94±0.33 mgEq/100mg extract. Several studies demonstrated the involvement of flavonoids in the regulation of blood sugar and diabetes complications.

Antiatherosclerotic Activity of Methanolic Extract of Woodfordia fructicosa Flowers

In the present investigation the methanolic extract of Woodfordia fructicosa flowers at the doses of 100, 200 and 400 mg/kg was investigated for antiatherosclerotic against high fat diet induced atherosclerosis and triton induced atherosclerosis. In high fat diet induced atherosclerosis several parameters of lipid profile such as total cholesterol (TC) and triglycerides (TG), lipoprotein profile such as low density lipoprotein cholesterol (LDLc), very low density lipoprotein cholesterol (VLDLc) and high density lipoprotein cholesterol (HDLc), atherosclerotic markers such as alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) and atherogenic index parameters such as TC/HDLc, LDLc/HDLc were determined and found to significantly altered in induction control group treated with high fat diet. The histopathological studies of liver and heart tissue were also performed wherein high fat diet showed toxic effects on cardiac and hepatic tissue. Similarly, in triton induced atherosclerosis parameters of lipid profile such as total cholesterol, triglycerides, low density lipoprotein and very low density lipoprotein levels were determined and were found to be significantly increased in induction control group. methanolic extract of Woodfordia fructicosa flowers showed protection against the atherosclerosis by bringing back the altered parameters to normal I both the models and showing ameliorating effects against high fat diet induced hepatic and cardiac damage. The multistep putative action of methanolic extract of flowers of Woodfordia fructicosa is attributed to the prominent phytoconstituents namely ellagic acid estimated through HPTLC analysis of the extract. Thus the study exhibited the protective effect of methanolic extract of flowers of Woodfordia fructicosa against atherosclerosis.

Histopathological Study of Liver and Kidney Tissues in C57 Mice via Chronic Exposure to Cadmium and Zinc.

Heavy metals have a wide application in the industrial world, affecting the health and longevity of living organisms. The current study assessed the possible effects of Cadmium (Cd) and Zinc (Zn) on the liver and kidney. Therefore, 150 male and female white mice C57BL were treated in three different groups with 0.685 mg/L CdCl2. 2.5H2O (group 1), and 0.567 mg/L ZnSO4.7H2O (group 2) in drinking water, while the control group only received water for 90 days to investigate how these elements accumulated in the liver/kidney and evaluate the possible histological changes in the liver and kidney. During 90 days, the histopathological consequences of Cd and Zn on the liver and kidneys were recorded. The results pointed out that exposure to heavy metals, such as Cd and Zn, led to organ accumulation of these elements. The histological evaluations demonstrated significant detrimental effects on the liver and kidney. Under the influence of Cd, light microscopic examination revealed significant histological alterations in both organs. In the animals exposed to Cd and Zn, histopathological alterations were observed in the liver, including extensive degeneration, necrosis, depletion, and necrosis of hepatocytes with significant nuclear hypertrophy. When animals are exposed to Cd and Zn, histological alterations in the kidneys include severe vascular degeneration and renal tubule necrosis. In conclusion, heavy metal intoxication has been shown to cause histopathological changes in the liver and kidneys of experimental animal models.

Homalium zeylanicum attenuates streptozotocin-induced hyperglycemia and cellular stress in experimental rats via attenuation of oxidative stress imparts inflammation

Ethnopharmacological relevanceHomalium zeylanicum (Gardner) Benth (Salicaceae) leaves are being used as folklore medicine to treat diabetes by the local folk of Andhra Pradesh, India. The medicinal claim of this plant with hypoglycaemic effects was initially studied by the authors. Results demonstrated the important antioxidant activities of the hydroalcohol fraction of leaves of H. zeylanicum leaves (HAHZL) were positively correlated with phenols and flavonoids contents. Aim of the studyBased on the previous findings, additional research is needed to examine the efficacy of using HAHZL to treat hyperglycemia. We therefore investigated in vitro and in vivo glycemic response of HAHZL, and evaluation of possible mechanism of bioactive molecules in mitigating streptozotocin-induced cellular stress in experimental rats via attenuation of oxidative stress imparts inflammation. MethodsGC-MS/MS analysis of HAHZL was carried out to identify bioactive constituents. In vitro antidiabetic (α-glucosidase, α-amylase) and anti-inflammatory activities were investigated. HFD/low-STZ-prompted diabetic Wistar rats were administered with HAHZL (300 and 400 mg/kg; oral) for 28 days. Blood serum, oxidative stress, inflammation, DNA damage, and antidiabetic markers of pancreas and liver were determined. Histopathological studies of liver and pancreas were performed to assess the protective role of HAHZL. ResultsGC-MS/MS study revealed 7 bioactive compounds e.g., Phenol, 4-ethenyl-, acetate (28.68%), hydroquinone (9.10%), n-hexadecanoic acid (0.55%), phytol (0.57%), arbutin (17.65%), Vitamin E (1.04%), β-Sitosterol (1.54%) which possess antioxidant, anti-inflammatory and anti-diabetic activities. HAHZL showed significant in vitro glycemic response as evidenced by the inhibition of α-amylase, and α-glucosidase activities. Lineweaver-Burk plot revealed that HAHZL exhibited competitive and mixed competitive inhibition towards α-amylase and α-glucosidase, respectively. HAHZL at 400 mg/kg modulated the pathophysiology associated with HFD/STZ-induced type2 diabetes mellitus and significantly (p < 0.001) improved antihyperglycemic (SG, SI, HOMA-IR, and HbA1C), antidyslipidemic (TC, HDL-C, LDL-C, and TG), antioxidative (MDA, SOD, CAT, GSH, and 8-OHdG) and anti-inflammatory (TNF-α, and CRP) markers in serum, pancreas and liver. In vitro and in vivo test results were corroborated by the improvement of pancreatic and hepatic tissue architecture in diabetic rats. ConclusionHAHZL bearing bioactive components phenol, 4-ethenyl-,acetate, hydroquinone, n-hexadecanoic acid, arbutin, phytol, vitamin E and β-sitosterol balanced glycemic level by normalising the levels of glycaemic indices, lipid profile, pancreas and liver functional markers in STZ-induced T2DM rats.

Sustained In Vitro and In Vivo Delivery of Metformin from Plant Pollen-Derived Composite Microcapsules.

We developed a dual microencapsulation platform for the type 2 diabetes drug metformin (MTF), which is aimed to increase its bioavailability. We report the use of Lycopodium clavatum sporopollenin (LCS), derived from their natural spores, and raw Phoenix dactylifera L. (date palm) pollens (DPP) for MTF microencapsulation. MTF was loaded into LCS and DPP via a vacuum and a novel method of hydration-induced swelling. The loading capacity (LC) and encapsulation efficiency (EE) percentages for MTF-loaded LCS and MTF-loaded DPP microcapsules were 14.9% ± 0.7, 29.8 ± 0.8, and 15.2% ± 0.7, 30.3 ± 1.0, respectively. The release of MTF from MTF-loaded LCS microcapsules was additionally controlled by re-encapsulating the loaded microcapsules into calcium alginate (ALG) microbeads via ionotropic gelation, where the release of MTF was found to be significantly slower and pH-dependent. The pharmacokinetic parameters, obtained from the in vivo study, revealed that the relative bioavailability of the MTF-loaded LCS-ALG beads was 1.215 times higher compared to pure MTF, following oral administration of a single dose equivalent to 25 mg/kg body weight MTF to streptozotocin (STZ)-induced diabetic male Sprague-Dawley rats. Significant hypoglycemic effect was obtained for STZ-induced diabetic rats orally treated with MTF-loaded LCS-ALG beads compared to control diabetic rats. Over a period of 29 days, the STZ-induced diabetic rats treated with MTF-loaded LCS-ALG beads showed a decrease in the aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglycerides, cholesterol, and low-density lipoprotein-cholesterol (LDL-C) levels, as well as an increase in glutathione peroxidase (GPx) and a recovery in the oxidative stress biomarker, lipid peroxidation (LPx). In addition, histopathological studies of liver, pancreas, kidney, and testes suggested that MTF-loaded LCS-ALG beads improved the degenerative changes in organs of diabetic rats. The LCS-ALG platform for dual encapsulation of MTF achieved sustained MTF delivery and enhancement of bioavailability, as well as the improved biochemical and histopathological characteristics in in vivo studies, opening many other intriguing applications in sustained drug delivery.