Damage In Experimental Rats Research Articles

Astragalin Nanoparticles Ameliorates CCl4 - Induced Liver Fibrosis in Rats

Liver plays a vital role in the elimination of xenobiotics that can induce hepatotoxicity in living organisms. Polymeric nanoparticles have evolved recently as an alternative in various industries and are used for their biomedical applications. Astragalin is a least studied flavonoid that has been used in the traditional medicine of Southeast Asia for its healing properties. Hence, in this study we used carbon tetrachloride as a hepatotoxin to induce liver damage. The protective effects of astragalin loaded polymeric nanoparticles on hepatotoxin-induced liver damage in experimental rats were assessed. The results of the assessment indicate that astragalin nanoparticles were effective in protecting the liver from damages induced by carbon tetrachloride. Astragalin nanoparticles formulation is not available in the market. Among existing literature, this is the first ever approach for hepatoprotective effect of astragalin nanoparticles studied.

Butin prevent liver damage triggered by D-galactosamine via regulating lipid peroxidation and proinflammatory cytokines in rodents

ObjectivesLiver damage is becoming a more severe problem around the world. Unfortunately, there is still a great need for clinically effective pharmacological therapy for liver injury. The investigation aimed to assess the favorable outcome of butin hepatoprotective efficacy against D-galactosamine (D-GalN)-produced liver damage in experimental rats. MethodsA single dose of D-GalN 400 mg/kg b. wt. was injected intraperitoneally, 24 hr prior to scarification of rats to cause liver damage. The liver injury was assessed biochemically, investigating parameters like aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT), γ-glutamyl transferase (GGT), total-bilirubin, -albumin and -protein. Butin (25 and 50 mg/kg b. wt.) was managed for 21st days and at the end of the experimental period, normal control, D-GalN control, and butin treatment group rats for further biochemical as well as histopathological consideration. ResultsButin pretreatment significantly attenuated D-GalN-induced hepatocytes damage by reducing hepatic markers and its ability in attenuating oxidative damage (MDA, GSH, SOD, CAT) and pro-inflammatory cytokine (TNF-α, IL-6, IL-1β) and MPO. Histopathological assessment of the liver and biochemical estimation confirmed the hepatoprotective effects of butin. Conclusions: These results demonstrated that butin protects experimental rats against D-GalN-induced liver injury by modulating lipid peroxidation and pro-inflammatory cytokine. Current research will give preliminary experimental evidence for butin, and possible therapeutic effects in liver disorders.

Methanol Stem Bark Extract of Ficus platyphylla Protects Against Carbon Tetrachloride-Induced Liver Damage in Wistar Rats

Ficus platyphylla (Gutta percha tree) is used in Nigerian traditional medicine for treating pain and psychosis. This study evaluated the protective effect of methanol stem bark extract of Ficus platyhylla (MEFP) against carbon tetrachloride (CCl4)-induced liver injury in Wistar rats. Rats were allotted into six groups namely normal control, negative control, standard drug (silymarin) and extract treated (100, 200 and 400 mg/kg p.o. respectively) groups. Treatment was administered for 7 days. Animals in groups II-VI received a single dose of CCl4 (1:1) p.o. in olive oil at 1.5 ml/kg body weight after last treatment. Experimental rats were sacrificed after 24 hours of CCl4 administration and blood samples collected for determination of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Supernatant of liver homogenate was used to determine activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx). Results indicate increased activities (p < 0.05) in CAT, SOD and GPx in samples of MEFP treated rats while levels of ALT and AST in serum samples of treated groups differ significantly (p<0.05) when compared with negative control group (Group III). Treatment with methanol stem bark extract of Ficus platyphylla may have offered protection against CCl4 induced liver damage in experimental rats.

Hepatoprotective Screening of Seriphidium kurramense (Qazilb.) Y.R. Ling.

Investigation on medicinal plants' therapeutic potential has gained substantial importance in the discovery of novel effective and safe therapeutic agents. The present study is aimed at investigating the hepatoprotective potential of Seriphidium kurramense methanolic extract (SKM) against carbon tetrachloride- (CCl4-) induced hepatotoxicity in rats. S. kurramense is one of the most imperative plants for its various pharmacological activities. Therefore, this study was aimed at evaluating the hepatoprotective potential against CCl4-induced liver toxicity. The serum samples were analyzed for alanine aminotransferase (ALT) and aspartate aminotransferase (AST) together with the oxidative stress mediator levels as nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), reduced glutathione (GSH), and superoxide dismutase (SOD) as well as peroxidation and H2O2 activity. CCl4 administration resulted in an elevated free radical generation, altered liver marker (AST and ALT) enzymes, reduced antioxidant enzyme, and increased DNA damage. Methanolic extract of S. kurramense decreased CCl4-induced hepatotoxicity by increasing the antioxidant status and reducing H2O2 and nitrate content generation as well as reducing DNA damage. Additionally, SKM reversed the morphological alterations induced by CCl4 in the SKM-treated groups. These results demonstrated that SKM displayed hepatoprotective activity against CCl4-induced hepatic damage in experimental rats.

EXTENUATING EFFECTS OF Terminalia catappa LEAVES AND Persea americana SEED EXTRACTS ON STREPTOZOTOCIN-INDUCED LIPIDS PERTURBATION AND PANCREATIC DAMAGE IN DIABETIC RATS

Diabetes mellitus develops either due to insufficient insulin secretion or lack of insulin resulting from damaged pancreas beta cells. Dyslipidaemia is an acute complication in diabetes mellitus. The aim of this study was to investigate the extenuating effects of T. cattapa leaves and P. americana seed aqueous extracts on streptozotocin-induced lipids profile perturbation and pancreatic damage in experimental rats. Thirty male albino rats were randomly divided into six groups (n = 5). Group 1: (negative control), group 2: 80 mg/kgbwt streptozotocin (positive control), group 3: (80 mg/kgbwt streptozotocin + 200 mg/kgbwt T. catappa leave extract), group 4: (80 mg/kgbwt streptozotocin + 200 mg/kgbwt Persea americana seed extract), group 5: (80 mg/kgbwt streptozotocin + 200 mg/kgbwt extracts-mixture), group 6: (80 mg/kgbwt streptozotocin + 5 mg/kgbwt glibenclamide (standard drug). A single dose of streptozotocin was administered to the rats intraperitoneally; the extracts and glibenclamide were administered orally for 21 days, after which their pancreas was excised for histology. Thereafter, extracts of T. catappa leaves and P. americana seed on serum lipid levels imbalance in streptozotocin-induced diabetic rats were investigated. Histological studies showed a degenerative effect of the pancreatic islet cells of strotozotocin-induced groups. Results showed improvement in the regulation of lipid metabolism as well as the regeneration of the beta cells of pancreas on treatment with T. catappa leaves and P. americana seed. The extracts both equally exert significant antidyslipidemic effects in diabetic rats, in view of the extenuating effects of the extracts on pancreatic islet cells.

Korean Red Ginseng (Panax ginseng Meyer) with enriched Rg3 ameliorates chronic intermittent heat stress–induced testicular damage in rats via multifunctional approach

BackgroundPanax ginseng Meyer, known as Korean Red Ginseng (KRG), is one of the important age-old traditional herbs used in boosting libido and improving male fertility. In this study, the effects of Rg3-enriched KRG extract (KGC04P) on heat stress–induced testicular damage in experimental rats was evaluated. MethodsMale rats (Sprague-Dawley) were divided into four groups (n = 10): normal control (NC), heat-stressed control (HC), heat-stressed plus KGC04P-100 mg/kg (HK100), and heat-stressed plus KGC04P-200 mg/kg (HK200) groups. Starting 1 week prior to heat stress, animals were administered orally with KGC04P (100 and 200 mg/kg) mixed with a regular pellet diet and continued for 25 weeks. Heat stress was induced to HC, HK100, and HK200 groups by intermittently exposing the animals to high temperatures (32 ± 1°C, 2 h/day). After 6 months, animals were euthanized under general anesthesia with carbon dioxide and evaluated for various parameters in serum and testicular tissue by using Western blotting, biochemical kits, and reverse transcription-polymerase chain reaction. ResultsSignificant (p < 0.05) alterations in several parameters, such as body/organ weight, sperm kinematics, and lipid metabolism marker levels, in the serum and testis of rats were observed. Further, the expression of testicular antioxidant enzymes, inflammatory cytokines, sex hormonal receptors, and spermatogenesis-related genes were also affected significantly (p < 0.05) in the heat-stressed group. However, KGC04P prevented the heat stress–induced changes in rats significantly (p < 0.05) at both concentrations. ConclusionKGC04P attenuated heat stress–induced testicular damage by a multifunctional approach and can be developed as an excellent therapeutic agent for hyperthermia-mediated male infertility.

Protective effect of betulinic acid against intracerebroventricular streptozotocin induced cognitive impairment and neuronal damage in rats: Possible neurotransmitters and neuroinflammatory mechanism.

The purpose of the study was to explore the therapeutic potential of Betulinic acid (BA) in streptozotocin (STZ) induced memory damage in experimental rats. STZ (3mg/kg bilaterally) as intracerebroventrical (icv) route was administered on day 1 and 3 in rats. Donepezil (5mg/kg/day po), used as standard, and BA (5, 10 and 15mg/kg/day po) were administered after 1h of 1st STZ infusion up to 21days. Object recognition task (ORT) for non-spatial, Morris water maze (MWM) for spatial and locomotor activity were performed to evaluate behavioral changes in rats. On 22nd day, animals were decapitated and hippocampus was separated to perform biochemical (AChE, LPO, GSH, nitrite), neuroinflammatory (TNF-α, IL-1β, and IL-6), neurotransmitters (NTs) (dopamine, norepinephrine and serotonin) analysis. STZ infusion significantly impaired memory as observed in MWM and ORT, increased oxidative stress, pro-inflammatory cytokine's level and altered NTs level. Moreover, BA demonstrated a neuroprotective effect in a dose-dependent manner. BA dose dependently (5, 10 and 15mg/kg) significantly restore STZ induced memory changes and pathological abnormalities in rat brain. The findings of the current study suggests that BA protect rat brain from STZ induced neuronal damage via acting through multiple mechanisms and would be used to curb cognitive decline associated with neurodegenerative disorders especially AD.

Simvastatin ameliorates cognitive impairments via inhibition of oxidative stress‑induced apoptosis of hippocampal cells through the ERK/AKT signaling pathway in a rat model of senile dementia.

Senile dementia is a degenerative disease of the nervous system associated with cognitive impairments, memory disorders, executive dysfunctions, cognitive decline and dementia. Previous reports suggested that simvastatin presents ameliorative effects in the progression of senile dementia. However, the mechanism underlying simvastatin‑mediated improvements of cognitive competence during the progression of senile dementia remains to be elucidated. In the present study, a potential mechanism underlying simvastatin activity in hippocampal cells, was investigated. Results of the present study demonstrated that simvastatin significantly improved cognitive impairments, memory competence, amyloid plaques, loss of neurons and synapses, neurofibrillary tangles and oxidative damage in experimental rats. Results of the present study demonstrated that administration of simvastatin regulates superoxide dismutase, reactive oxygen species, catalase and glutathione in oxidative stress processes in hippocampal cells. Apoptosis of hippocampal cells was suppressed by simvastatin treatment in rats with senile dementia. Notably, the administration of simvastatin inhibited activating transcription factor‑6‑mediated extracellular signal‑regulated kinase/AKT serine/threonine kinase (ERK/AKT) signaling pathway in hippocampal cells. Taken together, the preclinical results of the present study indicate that simvastatin is efficient in preventing memory lapse and inhibiting apoptosis of hippocampal cells via the ERK/AKT signaling pathway, which may in the future improve cognitive decline and dementia in patients.

Protective effects of Korean Red Ginseng against sub-acute immobilization stress-induced testicular damage in experimental rats

BackgroundExcessive stress causes varied physiological and psychological disorders including male reproductive problems. Here, we attempted to investigate the protective effects of Korean Red Ginseng (Panax ginseng Meyer; KRG) against sub-acute immobilization stress-induced testicular damage in experimental rats. MethodsMale rats (age, 4 wk; weight, 60–70 g) were divided into four groups (n = 8 in each group): normal control group, immobilization control group, immobilization group treated with 100 mg/kg of KRG daily, and immobilization group treated with 200 mg/kg of KRG daily. Normal control and immobilization control groups received vehicle only. KRG (100 mg/kg and 200 mg/kg) was mixed in the standard diet powder and fed daily for 6 mo. Parameters such as organ weight, blood chemistry, sperm kinematic values, and expression levels of testicular-related molecules were measured using commercially available kits, Western blotting, and reverse transcription polymerase chain reaction. ResultsData revealed that KRG restored the altered testis and epididymis weight in immobilization stress-induced rats significantly (p < 0.05). Further, KRG ameliorated the altered blood chemistry and sperm kinematic values when compared with the immobilization control group and attenuated the altered expression levels of spermatogenesis-related proteins (nectin-2, cAMP responsive element binding protein 1, and inhibin-⍺), sex hormone receptors (androgen receptor, luteinizing hormone receptor, and follicle-stimulating hormone receptor), and antioxidant-related enzymes (glutathione S-transferase m5, peroxiredoxin-4, and glutathione peroxidase 4) significantly in the testes of immobilization stress-induced rats. ConclusionKRG protected immobilization stress-induced testicular damage and fertility factors in rats, thereby indicating its potential in the treatment of stress-related male sterility.

Teratogenic Effect of Artesunate on the Morphometric Parameters of the Body and Developing Olfactory Bulb of Wistar Rats Following Maternal Oral Administration

Artesunate an antimalarial drug has been reported to cause irreversible brain damage in experimental rats, and to cause other toxic effects like haemolysis and neutropenia. This study was conducted to investigate the morphometric teratogenic effect of the antimalarial agent artesunate (ARTS) on the developing olfactory bulb of Wistar rats following maternal oral administration. A total of 16 virgin female and 8 male Wistar rats weighing 150 g were used for this study. The oestrous cycle of the female rats were determined and at the proestrous phase they were allowed to mate with the male overnight. Pregnant rats were administered ARTS daily from gestational day 8-12 via oral gavages, at test doses of 0, 2, 4, or 8 mg/kg (4 females per group). The results showed significant reduction in the crown-rump length, hind-limb length, fore-limb length and organ-body weight ratio in the pups. There was significant decrease in the length, width, thickness, and weight of the olfactory bulb at &lt;0.001, which was dose dependent, with more effect on the 8 mg/kg group than in the 2 mg/kg group. The effect of artesunate was dose dependent, and has been shown to significantly decrease the crown-rump length, fore-limb length, hind-limb length, and organ body weight ratio of the pups and it also significantly decreased the weight, length, thickness and width of the olfactory bulb with no observable adverse effect level to the 2 mg/kg/day group, thus ARTS might affect embryo and foetal development.

Attenuation of Doxorubicin-induced Oxidative Stress and Organ Damage in Experimental Rats by Theobroma cacao Stem Bark

Attenuation of Doxorubicin-induced Oxidative Stress and Organ Damage in Experimental Rats by Theobroma cacao Stem Bark

Influence of alpha-lipoic acid on nicotine-induced lung and liver damage in experimental rats.

Nicotine mediates some of the injurious effects caused by consuming tobacco products. This work aimed at investigating the defensive role of alpha-lipoic acid (ALA) with its known antioxidant and antiinflammatory effect in nicotine-induced lung and liver damage. Rats were arranged into 4 groups: control, nicotine, ALA, and ALA-nicotine groups. Oxidative stress and antioxidant status were determined by assessing thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), and glutathione (GSH) levels in lung and liver. Liver enzymes and lipid profiles were measured and pulmonary and hepatic damage were assessed by histopathological examination. Also, serum levels of transforming growth factor beta 1 (TGF-β1) and vascular cell adhesion molecule 1 (VCAM-1) were determined. The results revealed an increase in TBARS in tissues and a reduction in both SOD and GSH activity in the nicotine-treated rats. Nicotine induced high levels of liver enzymes, TGF-β1, VCAM-1, and dyslipidemia with histopathological changes in the lung and liver. ALA administration along with nicotine attenuated oxidative stress and normalized the SOD and GSH levels, ameliorated dyslipidemia, and improved TGF-β1 and VCAM-1 with better histopathology of the lung and liver. The study data revealed that ALA may be beneficial in alleviating nicotine-induced oxidative stress, dyslipidemia, and both lung and liver damage.

RETRACTED ARTICLE: Neuropathological and neuroprotective features of vitamin B12 on the dorsal spinal ganglion of rats after the experimental crush of sciatic nerve: an experimental study

BackgroundSpinal motoneuron neuroprotection by vitaminB12 was previously reported; the present study was carried out to evaluate neuroprotectivity in the dorsal root ganglion sensory neuron.MethodsIn present study thirty-six Wister-Albino rats (aged 8–9 weeks and weighing 200–250 g) were tested. The animals were randomly divided into 6 groups which every group contained 6 rats. Group A: received normal saline (for 42 days); Group B: vitamin B12 was administered (0.5 mg/kg/day for 21 days); Group C: received vitamin B12 (1 mg/kg/day for 21days); Group D: received vitamin B12 (0.5 mg/kg/day for 42 days); Group E; received vitamin B12 (1 mg/kg/day for 42 days); Group F; received no treatment. The L5 Dorsal Root Ganglion (DRG) neurons count compared to the number of left and right neurons .Furthermore, DRG sensory neurons for regeneration were evaluated 21 or 42 days after injury (each group was analyzed by One-Way ANOVA test).Results(1): The comparison of left crushed neurons (LCN) number with right non-crushed neurons in all experimental groups (B, C, D and C), indicating a significant decline in their neurons enumeration (p<0/05). (2): The comparison of test group’s LCN with the control group’s LCN revealed a significant rise in the number of experimental group neurons (p<0/05). (3): Moreover, comparing the number of right neurons in experimental groups with the number of neurons in crushed neurons indicated that the average number of right neurons showed a significant increase in experimental groups (p<0/05).ConclusionConsequently, the probability of nerve regeneration will be increased by the increment of the administered drug dosage and duration. On the other hand, the regeneration and healing in Dorsal Spinal Ganglion will be improved by increase of administration time and vitamin B12 dose, indicating that such vitamin was able to progress recovery process of peripheral nerves damage in experimental rats. Finally, our results have important implications for elucidating the mechanisms of nerve regeneration. Moreover, the results showed that vitaminB12 had a proliferative effect on the dorsal root ganglion sensory neuron.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7395141841009256

Cytoprotective effects of Bauhinia purpurea leaf extract against ethanol-induced gastric mucosal ulcer in rats

Bauhinia purpurea is a medicinal plant commonly used traditionaly in the treatment of many ailments. The present study was undertaken to evaluate the protective effect of ethanolic extracts of B. purpurea ethanolic leaf extract (BPELE) against absolute ethanol-induced gastric mucosal damage in experimental rats. The rats were divided into four groups, respectively pre-treated orally with carboxymethyl cellulose solution (ulcer control groups), omeprazole 20 mg/kg (reference group), 250 and 500 mg/kg of BPELE (experimental groups) 1 h before oral administration of absolute ethanol to generate gastric mucosal damage. After an additional hour, the rats were sacrificed and the ulcer areas of the gastric walls were determined. The ulcer control group exhibited severe mucosal injury, whereas groups pre-treated with B. purpureaethanolic leaf extract exhibited significant protection of gastric mucosal damage. These findings were also confirmed by histology of gastric wall. Significant increases in gastric mucus production and decrease in acidity of gastric content were observed in treated groups with BPELE compare to ulcer control group. These results concluded that the treatment with BPELE prior to absolute alcohol has significantly protect gastric mucosa as ascertained grossly by significant reduction of ulcer area,increases in gastric mucus production and deecrease the acidity of gastric content and histology by comparatively decreases in gastric mucosal damage, reduction or absence of edema and leucocytes infiltration of submucosal layer compared to ulcer control group. BPELE was able to decrease the acidity and increase the mucosal defense in the gastric area thereby justifying its use as an antiulcerogenic agent. Key words: Bauhinia purpurea, cytoprotection, gastric ulcer, mucosal defense, histology.

Differential oxidative stress responses to methanol in intraperitoneally exposed rats: ameliorative effects of Opuntia vulgaris fruit extract

Methanol is primarily metabolized by oxidation to formaldehyde and then to formate. These processes are accompanied by formation of superoxide anion and hydrogen peroxide. This article reports data on the effect of methanol-induced oxidative damage in experimental rats and the role of aqueous extract of Opuntia vulgaris fruit extract (OE) to counteract the toxicity induced by methanol. The animals were exposed to methanol at a dose of 2.37 g/kg body weight intraperitoneally for 30 days. OE was found to contain large amounts of polyphenols and carotenoids and significant antioxidant capacities highlighted by scavenging activities for 2,2-diphenyl-l-picrylhydrazyl. The treatment with methanol exhibited a significant increase in serum hepatic and renal biochemical parameters (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, bilirubin, urea, and creatinine). Methanol intoxication significantly increased hepatic and renal lipid peroxidation evaluated by thiobarbituric acid reactive substances in treated rats as compared to controls. However, hepatic and renal antioxidant enzymes namely superoxide dismutase, catalase, and glutathione peroxidase were significantly decreased in methanol-treated animals as compared to controls. The results concluded that treatment with OE prior to methanol intoxication has significant role in protecting animals from methanol-induced hepatic and renal histopathological and oxidative damage.

Hepatoprotective role and antioxidant capacity of selenium on arsenic-induced liver injury in rats

The present study was undertaken to evaluate the protective effect of selenium against arsenic-induced oxidative damage in experimental rats. Males were randomly divided into four groups where the first was served as a control, whereas the remaining groups were respectively treated with sodium selenite (3 mg/kg b.w.), sodium arsenite (5.55 mg/kg b.w.) and a combination of sodium arsenite and sodium selenite. Changes in liver enzyme activities, thiobarbituric acid reactive substances (TBARS) level, antioxidants and reduced glutathione (GSH) contents were determined after 3 weeks experimental period. Exposure of rats to As caused a significant increase in liver TBARS compared to control, but the co-administration of Se was effective in reducing its level. The activities of glutathione peroxidase (GPx) and glutathione-S-transferase (GST) of As-treated group were found lower compared to the control and the Se-treated group. The co-administration of Se had an additive protective effect on liver enzyme activities compared to As-treated animals. On the other hand, a significant increase in plasmatic activities of AST, ALT and ALP was observed in As-treated group. The latter was also exhibited a decrease in body weight and an increase in liver weight compared to the control. The co-administration of Se has decreased the activities of AST, AST and ALP and improved the antioxidant status as well. Liver histological studies have confirmed the changes observed in biochemical parameters and proved the beneficial role of Se. To conclude, results suggest that As exposure enhanced an oxidative stress by disturbing the tissue antioxidant defense system, but the Se co-administration protected liver tissues against As intoxication probably owing to its antioxidant properties.

Hepatoprotective effects of Garcinia kola seed against hepatotoxicity induced by carbon tetrachloride in rats

The protective effects of Garcinia kola against a dose of Carbon-Tetrachloride (CC14)- induced liver damage in experimental rats were investigated. The CC14 induction (administered intraperitoneally, 0.5m1/kg body weight in olive oil-0.5ml/kg body weight) ledto significant increases in the levels of serum aspartate and alanine amino transferases, alkaline phosphatase and lipid peroxides in CC14 intoxicated rats. Pretreatment with varied concentrations of Garcinia kola diets (1%, 5% and 10%) and vitamin E (9%,) for 21 days prior to CC14 administration resulted in significant decreases in Liver marker enzymes and lipid peroxides. These findings suggest that Garcinia kola seed may be acting as a natural antioxidant that prevents hepatic oxidative stress induced by CC14