Alterations In Wistar Rats Research Articles

Retraction Note: Flavonoid fractions of diosmin and hesperidin mitigate lead acetate-induced biochemical, oxidative stress, and histopathological alterations in Wistar rats.

[This retracts the article DOI: 10.1007/s43188-020-00084-9.].

Supplementation of Chlorella vulgaris Ameliorates the Stress-induced Hematological Alterations in Wistar Rats

Stress has been associated with various diseases and physiological disruptions. Chlorella vulgaris is known for its antioxidant properties. This study examined the effects of C. vulgaris on the hematological profile of stress-induced Wistar rats. Stress significantly impacted various hematological parameters, including erythrocyte count, hemoglobin concentration, hematocrit levels, white blood cell count, and platelet count. The supplementation of cultivated C. vulgaris effectively restored erythrocyte count and suppressed elevated lymphocyte levels, while commercially available C. vulgaris and amitriptyline drugs had no significant effects on these parameters. Stress caused smaller-sized erythrocytes but did not significantly affect mean corpuscular volume. Both amitriptyline and C. vulgaris restored platelet levels, while mean platelet volume remained unaffected. Overall, C. vulgaris showed promise as a therapeutic intervention for countering stress-induced inhibition of erythropoiesis and restoring erythrocyte count, but more research is needed to understand the underlying mechanisms and develop effective strategies for managing stress-related changes in hematological parameters.

Chronic caffeine intake alters collagen deposition in long bones: an experimental preliminary study

This study explores the impact of chronic caffeine intake on collagen deposition in long bones and correlates it with morphometric and metabolic alterations in Wistar rats. Animals had either regular drinking water (Control group) or caffeinated drinking water in a 300 mg/L dose (Caffeine group) for 12 wk. Using Picro-Sirius red collagen staining, cortical (78.07 ± 1.27 vs 82.12 ± 1.22) and trabecular (74.29 ± 1.09 vs 77.97 ± 1.03) collagen percentages in the caffeine group were markedly (p = 0.0448 and p = 0.0351; respectively) lower than the control group. Caffeine intake induced apparent alterations in the microstructure of cortical diaphysis and femoral head trabecular density as determined by micro-CT. In caffeinated animals, levels of bone-related metabolic biomarkers including BALP (1.41 ± 0.06 vs 1.12 ± 0.07), CTX (313.5 ± 20.78 vs 224.3 ± 27.19), DPD (11.61 ± 0.72 vs 9.26 ± 0.62), BGP (10.35 ± 0.43 vs 9.14 ± 0.34), and TRAP (4.34 ± 0.08 vs 4.01 ± 0.11) were increased (p = 0.0136, p = 0.0262, p = 0.0343, p = 0.0571, and p = 0.0461; respectively) as compared to control animals. Except for BALP (p = 0.0175) and DPD (p = 0.0423), the Pearson correlation between collagen bone deposition and microstructures and metabolic changes was not statistically significant. Collectively, chronic caffeine consumption restricts cortical and trabecular collagen deposition in long bones leading to microstructure and metabolic alterations.

Effects of Quercetin on Aspirin-Induced Haemato-Biochemical Alterations in Wistar Rats

Aspirin is a non-steroidal anti-inflammatory drug (NSAID). Quercetin is natural flavonoid present in high concentration in herbal drugs, fruits and vegetables and demonstrating broad bio-pharmacological properties. This study was aimed to evaluate the ameliorative effects of quercetin (@ 100 & 200 mg/kg b.wt.) in aspirin (@ 100 mg/kg b.wt.) induced haemato- biochemical alterations in Wistar rats (n=36) over a period of 28 days. There was significant decrease in mean values of haemoglobin, packed cell volume, platelets and increase in total leucocyte count in aspirin treated rats (Gr. II) over the control group (Gr I) at 28th day of experiment. Similarly, in biochemical parameters also there was significant elevation in aspartate aminotransferase, alanine aminotransferase, urea and creatinine and significant decrease inmean values of total protein, albumin, triglyceride and cholesterol in aspirin treated rats. Administration of quercetin at higher dose rate of 200 mg/kg b.wt. for 28 days (Gr. III) along with the aspirin in Wistar rats prevented such alterations in different haemato-biochemical parameters as the values on day 28 were almost similar to those on day 0 and at par with control group. Hence, quercetin @ 200 mg/kg b.wt. along with aspirin @ 100 mg/kg b.wt. can be recommended to avoid aspirin induced health issues in high risk mammals.

A comparative study of neurobehavioral changes induced by rotenone through oral and intraperitoneal administration

Parkinson’s disease is one of the major neurological disorders seen worldwide and associated with many motor and nonmotor symptoms. Rotenone-induced motor and behavior impairments could involve the gut-brain axis which is emphasized in several recent works. To explore how oral and intraperitoneal rotenone toxicity impacts neurobehavioral alterations in Wistar rats. The effect of intraperitoneal (3 mg/kg body weight 21 days) and oral (50 mg/kg body weight for 28 days) rotenone toxicity in male Wistar rats on various neurobehavioral parameters viz., rotarod, actophotometer, rearing behavior and elevated plus maze was comparatively studied. The neurobehavioral studies such as the Rota-rod test, rearing behavior, Elevated plus maze (EPM), and Actophotometer were performed by following standard published protocols and by utilizing the facilities available at the Institution. Kruskal-Wallis one- way ANOVA on ranks with Student-Newman-Keul’s multiple comparisons was used. It was found that both oral and intraperitoneal rotenone treatments had a significant impact on neurobehavioral parameters when compared to their respective controls. Although there were few differences observed in the study set behavioral parameters between intraperitoneal and oral rotenone treatments, it was not significant. The study findings suggest that neurobehavioral alterations caused by oral or intraperitoneal rotenone toxicity are found to be significant. The fact that oral rotenone toxicity has gut-brain axis- related problems can also have a role in PD-related motor/movement and anxiety behavior dysfunctions.

Beneficial effects of Salvia officinalis essential oil on vanadium-induced testicular injury, DNA damage and histological alterations in Wistar rats.

Vanadium has been shown to catalyze the generation of reactive oxygen species. Since free radical production and lipid peroxidation are potentially important mediators in testicular physiology and pathophysiology, the present study was conducted to elucidate vanadium-induced oxidative damage in rat testis and the ameliorative role of Salvia officinalis essential oil (SEO) against the adverse effects of this heavy metal. Adult male Wistar rats were treated daily during 10days either with ammonium metavanadate (5mg/kg bw, intraperitoneally), SEO (15mg/kg bw, orally) or their combination. A group of rats receiving daily a saline solution served as a negative control. Vanadium treatment induced a significant decrease in body and reproductive organ weights, serum testosterone level and sperm number and motility. An increase in lipid peroxidation and protein oxidation as well as a marked inhibition in the activities of antioxidant enzymes in the testes and seminal vesicles indicated the occurrence of oxidative stress after vanadium toxicity. Histopathological changes in testis and seminal vesicles were also observed following vanadium administration. However, co-administration of SEO to vanadium-treated rats resulted in an appreciable improvement of these parameters, emphasizing the therapeutic effects of SEO. It can be suggested that SEO mitigates vanadium-induced reproductive damage due to its antioxidant capacity. Thus, we can hypothesize that SEO supplementation could protect against vanadium poisoning.

Amelioration of Chemical Induced Hepatic Injury by Vitex agnus castus ExtractAmelioration of Chemical Induced Hepatic Injury by Vitex agnus castus Extract

Objective: The liver is the major organ of detoxification of ingested materials such as food, beverages and drugs, thus it is prone to toxicity with attendant pathologies. We studied the ability of Vitex agnus castus plant extract to ameliorate the biochemical and structural alterations in Wistar rats with carbon tetrachloride-induced liver injury.
 Methods: Forty adult male Wistar rats were allotted into eight equal groups. Group1 was normal control (NC); Group 2 Liver injury without extract (LI). The remaining six groups were paired composite group of varying dosage of the plant extract (200 mg/kg, 400 mg/kg and 600 mg/kg). Only one member of each pair had induced liver injury. Consequently, the groups were Low extract without liver injury (LE), Low extract with liver injury (LEL); Medium extract without liver injury(ME)
 Medium extract with liver injury (MEL) and High extract without liver injury (HE),High extract with liver injury (HEL).The biochemical parameters evaluated were the liver function test {Total protein plus globulin and albumen fractions; liver enzymes- alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase}. Oxidative stress was evaluated by measuring the activities of antioxidants namely; Superoxide dismutase (SOD), Catalase, Malondialdehyde (MDA) and Glutathione Peroxidase (GPx).Histology of the harvested liver specimens was used to assess the structural alterations.
 Results: The mean liver weight was highest in the HEL group and significantly different from that of its control (HE) and NC.The mean serum total protein of all the groups were significantly higher than that of the NC.The mean aspartate amino transferase levels of the LEL, ME and MEL groups were significantly lower than that of the control while that of the HEL was significantly higher than those of the LEL and MEL. The results of alanine amino transferase were similar to those of aspartate amino transferase. The alkaline phosphatase levels in all the experimental groups were significantly depressed when compared with the control. Amongst the experimental groups, the serum alkaline phosphatase level was significantly raised than those of the LEL, and MEL groups.
 The glutathione (GSH) activities of LE, HE and HEL were significantly lower. While the glutathione peroxidase (GPX) activity of the control was significantly lower to those of groups LEL, ME, MEL and HEL.Histopathology of the liver showed preservation of the liver architecture with normal hepatocytes in all the groups.
 Conclusion: The ethanolic extract of Vitex agnus castus was able to reduce the severity of carbon tetrachloride induced liver injury in wistar rats.

Gallic acid protects against cadmium chloride-induced alterations in Wistar rats via the antioxidant defense mechanism

Context: Cadmium has been considered as one of the most hazardous toxic compounds with harmfully effect on the health of organisms. Aims: To evaluate the effects of gallic acid (GA) on the cadmium-induced liver and renal oxidative stress in Wistar rats. Methods: Twenty Wistar rats were grouped into four (A–D) of five rats. Rats in Group A, B, C and D were administered distilled water, 5 mg/kg bw cadmium chloride (CdCl2), CdCl2 + GA concurrently and GA (20 mg/kg bw) respectively and administered for 14 days. Biochemical parameters such as antioxidant enzyme activities, urea, creatinine and myeloperoxidase activity were determined. Results: In the urea, creatinine and MPO, there was a significant increase in the CdCl2 treated group. In the liver, the CdCl2 treated group reduced significantly the catalase activity and increased the reduced glutathione. The gallic acid group increased in the GSH level, SOD, and CAT activities and it also reduced significantly the MDA level. However, the co-administration of CdCl2 + GA had a considerably increase in the antioxidant enzymes. In the kidney, catalase activity and MDA level significantly decrease and increase respectively. The gallic acid also increases significantly the CAT and SOD activities while the MDA level was reduced. Co-administration of GA + CdCl2 had a substantial increase only in the SOD activity compared to the control. Conclusions: This study indicates that gallic acid was able to protect the alteration induced by cadmium chloride in the rat kidney and liver.

Levamisole, a cocaine cutting agent, induces acute and subchronic systemic alterations in Wistar rats

The use of the anthelmintic levamisole as a cocaine adulterant has been increasing worldwide. Complications caused by this association include systemic vasculitis, agranulocytosis, neutropenia, tissue necrosis, pulmonary hemorrhage, and renal injury. Data about toxicity of levamisole are scarce, therefore the aim of this study was to evaluate the acute and subchronic toxic effects of levamisole in rats. Male Wistar rats received saline or levamisole by intraperitoneal route at the doses of 12, 24 and 36 mg/kg in the acute toxicity test; and at 3, 6 and 12 mg/kg in the subchronic toxicity test. Toxicity was evaluated using behavioral, cognitive, renal, hematological, biochemical and histopathological parameters. Acute administration of levamisole caused behavioral and histopathological alterations. Subchronic administration caused behavioral, cognitive and hematological alterations (p < 0.0001 and p < 0.05, respectively), impairment of liver and kidney functions (p < 0.05), and changes of antioxidant defenses (p ≤ 0.0001). Both administrations produced toxic effects of clinical relevance, which make levamisole a dangerous cutting agent. Furthermore, the knowledge of these effects can contribute to the correct diagnosis and treatment of cocaine dependents with unusual systemic alterations.

Biosynthesized ZnO Nanoparticles Using Albizia lebbeck Extract Induced Biochemical and Morphological Alterations in Wistar Rats.

Nano-based particles synthesized via green routes have a particular structure that is useful in biomedical applications as they provide cheap, eco-friendly, and non-toxic nanoparticles. In the present study, we reported the effect of various concentrations of Zinc oxide nanoparticles synthesized using A. lebbeck stem bark extract (ZnO NPsAL) as stabilizing agent on rat biochemical profiles and tissue morphology. Adult Wistar rats weighing 170 ± 5 g were randomly classified into eight groups of five rats each; Group A served as a control fed with normal diet and water. Groups B1, B2, C1, C2, D1, D2, and E were treated with 40 mg/kg and 80 mg/kg of the 0.01, 0.05, and 0.1 M biosynthesized ZnO NPsAL and zinc nitrate daily by the gavage method, respectively. The rats were anesthetized 24 h after the last treatment, blood samples, kidney, heart, and liver tissues were collected for biochemical and histopathological analysis. The rats mean body weight, serum alkaline phosphatase, alanine aminotransferase, creatinine, urea, bilirubin, protein, albumin, globulin, total cholesterol, triacylglycerol, and high-density lipoprotein were significantly altered with an increased concentration of biosynthesized ZnO NPsAL when compared with the control group (p < 0.05; n ≥ 5). Furthermore, histopathological analysis of treated rats’ kidney, heart, and liver tissue revealed vascular congestion, tubular necrosis, inflammation, and cytoplasmic vacuolation. Biosynthesized ZnO NPsAL showed significant alteration in biochemical parameters and tissue morphology in rats with increasing concentrations of the nanoparticles.

Flavonoid fractions of diosmin and hesperidin mitigate lead acetate-induced biochemical, oxidative stress, and histopathological alterations in Wistar rats.

This study aims at investigating the protective effects of flavonoid fractions of diosmin and hesperidin in mitigating sub-chronic lead acetate-induced biochemical, oxidative stress, and histopathological alterations in adult male Wistar rats. Forty animals were randomly assigned into five groups, each consisting of eight animals. Group I animals was treated with deionised water only, group II, IV, and V were administered lead acetate 90mg/Kg body weight (1/20th of the LD50), groups III, and IV was administered Daflon (100mg/Kg), while group V was administered Daflon (200mg/Kg), 30min prior treatment with lead acetate. All treatments lasted for 42days. Blood lead levels, electrolyte parameters, zinc protoporphyrin (ZPP) levels, activities of antioxidant enzymes, and histopathology of vital organs, were evaluated following standard practice. Sub-chronic lead acetate exposure induced a decrease in levels of serum electrolytes, and activities of antioxidant enzymes, while blood lead levels, ZPP, and malondialdehyde levels were increased. Lead exposure also instigated marked variation in histopathology of vital organs. Conversely, co-treatment with graded doses of daflon improved the levels of blood lead, electrolytes, ZPP, activities of antioxidant enzymes, and histopathology of vital organs. Data obtained from the current study indicate that rats exposed to sub-chronic doses of lead acetate show increased blood lead levels, electrolyte imbalance, alongside impairment in ZPP levels, activities of antioxidant enzymes, and histopathology, while pretreatment using daflon mitigated the ensued perturbations. This, therefore, suggests that consumption of foods enriched with flavonoid fractions of diosmin and hesperidin may be beneficial for individuals inhabiting lead-polluted environments.

Neuroprotection by solanesol against ethidium bromide-induced multiple sclerosis-like neurobehavioral, molecular, and neurochemical alterations in experimental rats

Background: Multiple Sclerosis (MS) is an idiopathic chronic neuroinflammatory disease characterized by neurodegeneration that clinically presents motor neuron disabilities, memory, and cognitive dysfunction. Recent findings suggest that the down-regulation of SIRT-1 associated with the progression of MS. Solanesol (SNL) is an active phytoconstituent isolated from the plant Nicotiana tobacum, belonging to the Solanaceae family and a significant biosynthetic precursor to CoQ10 with potent antioxidant and neuroprotective properties. Chemically, it is a long-chain non-cyclic terpene alcohol that consists of nine isoprene units. Purpose: In the current study, we investigated the neuroprotective potential of SNL (40–80 mg/kg) in intracerebropeduncle (ICP) ethidium bromide (EB) induced MS-like neurobehavioral alterations in Wistar rats. Methods: Wistar rats were equally divided into six groups (n = 6) and treated with 0.1%/10μl of ethidium bromide injection for seven days. Long-term treatment with SNL shows neuroprotective potential by improving motor function, grip strength, memory and cognition. Results: Our findings are primarily related to the upregulation of SIRT-1 level and the myelin basic protein in the brain. In addition, SNL also modulates the level of apoptotic markers (caspase-3, Bax, Bcl-2) with mitochondrial-ETC complex dysfunction in the rat brain. Further, SNL decreased inflammatory cytokines (TNF-α, IL-1β), oxidative stress markers, and restored neurotransmitter levels. Our findings also reveal the neuroprotective effect of SNL by restoring gross pathological alterations and reducing the volume of demyelination in rats. Thus, the present study concludes that SNL as a SIRT-1 signaling activator has neuroprotective potential against EB-induced MS rats. Hence, SIRT-1 signaling may be an effective therapeutic target strategy for the treatment of MS. However, more investigations are needed to be carried out to prove these beneficial effects.

Effect of Emblica officinalis fruits against metallic-lead induced biochemical and hematological alterations in Wistar rats

Lead toxicity and related health issues have become global concern due to increased use of lead-based products in the modern world. Though attempts are being made to tackle this malady through many ways, the use of naturally occurring materials that are available locally is a subtle approach. In this investigation, the fruits of E. officinalis (EO) were studied for their potential in overcoming biochemical and hematological alterations caused by metallic lead in rat model. Four groups of rats, each containing six animals, were considered for the study. Group I served as normal control while to other groups (II– IV), metallic lead powder (100 ppm/rat) was orally administrated for 30 consecutive days. From day 31, the animals in groups III and IV were treated with EO in doses of 50 and 100 mg/kg body weight (p. o.), respectively, for the following seven days. Group II served as lead-treated control. On day 38, the animals in all groups were sacrificed and the blood was collected and serum separated. The changes in biochemical (aspartate aminotrasferase, alanine aminotrasferase, alkaline phosphatase, gamma glutamyltrasferase, total cholesterol, triglycerides, urea, creatinine and calcium) and hematological (red blood cell count, white blood cell count, hemoglobin, packed cell volume and platelet count) parameters were estimated. Lead treated animals in Group - II showed appreciable changes in hematological and biochemical parameters. Treatment with EO (50 and 100 mg/kg) significantly restored the changes in the above parameters to near normal values implying that the fruit of E. officinalis is an effective natural material to overcome widespread lead toxicity. This observation is further supported by histopathological studies of liver and kidney tissues wherein the distorted architecture, degeneration and other changes found in lead-treated animals were brought back to near normal stages by the treatment of EO.

Neuroprotection by luteolin and gallic acid against cobalt chloride-induced behavioural, morphological and neurochemical alterations in Wistar rats

Cobalt (Co) intoxication arising from occupational exposures and ion release from metal implants has been associated with neurological alterations such as cognitive decline, incoordination and depression. The present study evaluated the mechanisms of neuro-protection exerted by Luteolin (Lut; 100 mg/kg) and Gallic acid (GA; 120 mg/kg) in Wistar rats exposed to cobalt chloride (CoCl2) at 150 mg/kg for 7 consecutive days. Results indicate that CoCl2 induced neuro-behavioural deficits specifically by decreasing exploratory activities of CoCl2-exposed rats, increased anxiety, as well as significant reduction in hanging latency. Co-treatment with Lut or GA, however, restored these parameters to values near those of normal controls. Moreover, Lut and GA prevented CoCl2-induced increases in hydrogen peroxide (H2O2), malondialdehyde (MDA) and nitric oxide (NO) in the brain, while also restoring the activities of acetylcholinesterase, glutathione S-transferase (GST) and superoxide dismutase (SOD). In addition, Lut and GA produced significant reversal of CoCl2-induced elevation in levels of serum Interleukin 1 beta (IL-1β) and Tumor necrosis factor (TNFα). Meanwhile, immunohistochemistry revealed increased astrocytic expression of glial fibrillary acidic protein (GFAP), with intense calbindin (CB) D-28k staining and pronounced dendrites in the Purkinje cells. In contrast, the CoCl2 group was characterized by decreased number of neurons expressing CB and dendritic loss. Taken together, mechanisms of luteolin and/or gallic acid protection against Co toxicity involved restoration of Ca2+ homeostasis, acetylcholinesterase and antioxidant enzyme activities, as well as inhibition of lipid peroxidation in the brain.

High fat diet for induced dyslipidemia and cardiac pathological alterations in Wistar rats compared to Sprague Dawley rats

IntroductionWistar and Sprague Dawley (SD) rats are generally used as models for the cholesterol metabolism experiments. They are acceptable to high fat diet-induced disorders with individual variations, including dyslipidemia and abnormal cardiac pathology. ObjectiveTo compare the effects of high fat diet in inducing dyslipidemia and cardiac pathological alterations between Wistar and SD rats. MethodsWe compared the differences in plasma cholesterol levels and cardiac pathological alterations between Wistar and SD rats of standard diet (3.90 kcal/g) and high fat diet (5.40 kcal/g) after 4 weeks. ResultsSD rats fed with high fat diet showed significantly enhanced LDL concentration and the decreased HDL concentration when compared to Wistar rats. Additionally, SD rats showed cardiac pathological alterations such as infiltration of mononuclear cells referring to inflammatory response and high amounts of perivascular fat playing a key role in the impairment of vascular functions. ConclusionsOur results indicate that SD rats may be the more suitable model for dyslipidemia and alteration of cardiac pathology induced by high fat diet.

Anti-TNF-α Agent Tamarind Kunitz Trypsin Inhibitor Improves Lipid Profile of Wistar Rats Presenting Dyslipidemia and Diet-induced Obesity Regardless of PPAR-γ Induction.

The increasing prevalence of obesity and, consequently, chronic inflammation and its complications has increased the search for new treatment methods. The effect of the purified tamarind seed trypsin inhibitor (TTIp) on metabolic alterations in Wistar rats with obesity and dyslipidemia was evaluated. Three groups of animals with obesity and dyslipidemia were formed, consuming a high glycemic index and glycemic load (HGLI) diet, for 10 days: Obese/HGLI diet; Obese/standard diet; Obese/HGLI diet + TTIp (730 μg/kg); and one eutrophic group of animals was fed a standard diet. Rats were evaluated daily for food intake and weight gain. On the 11th day, animals were anesthetized and sacrificed for blood and visceral adipose tissue collection. TTIp treated animals presented significantly lower food intake than the untreated group (p = 0.0065), TG (76.20 ± 18.73 mg/dL) and VLDL-C (15.24 ± 3.75 mg/dL). Plasma concentrations and TNF-α mRNA expression in visceral adipose tissue also decreased in obese animals treated with TTIp (p < 0.05 and p = 0.025, respectively) with a negative immunostaining. We conclude that TTIp presented anti-TNF-α activity and an improved lipid profile of Wistar rats with dyslipidemia and obesity induced by a high glycemic index and load diet regardless of PPAR-γ induction.

High fat diet for induced dyslipidemia and cardiac pathological alterations in Wistar rats compared to Sprague Dawley rats

IntroductionWistar and Sprague Dawley (SD) rats are generally used as models for the cholesterol metabolism experiments. They are acceptable to high fat diet-induced disorders with individual variations, including dyslipidemia and abnormal cardiac pathology. ObjectiveTo compare the effects of high fat diet in inducing dyslipidemia and cardiac pathological alterations between Wistar and SD rats. MethodsWe compared the differences in plasma cholesterol levels and cardiac pathological alterations between Wistar and SD rats of standard diet (3.90 kcal/g) and high fat diet (5.40 kcal/g) after 4 weeks. ResultsSD rats fed with high fat diet showed significantly enhanced LDL concentration and the decreased HDL concentration when compared to Wistar rats. Additionally, SD rats showed cardiac pathological alterations such as infiltration of mononuclear cells referring to inflammatory response and high amounts of perivascular fat playing a key role in the impairment of vascular functions. ConclusionsOur results indicate that SD rats may be the more suitable model for dyslipidemia and alteration of cardiac pathology induced by high fat diet.

Neuroprotective influence of sitagliptin against cisplatin-induced neurotoxicity, biochemical and behavioral alterations in Wistar rats

Cisplatin has been extensively used as a chemotherapeutic agent since around 40 years, though its usage is limited due to severe adverse effects like neurotoxicity that might be because of oxidative stress. Hence, the present study was planned to investigate the possible protective role of sitagliptin against cisplatin-associated neurotoxic, biochemical, and behavioral alterations in male Wistar rats. Sitagliptin is a dipeptidyl peptidase-4 inhibitor that shows dual effects by improving the control on metabolism as well as decreasing the debility in cognitive function that is associated with increased insulin sensitivity and antioxidant property. For the in vitro assay, cultured rat pheochromocytoma (PC12) cells were exposed to different concentrations (10, 20, and 50mM) of sitagliptin for 24h. Cisplatin at 5mM concentrations was added and cell viability was assessed using MTT assay. For in vivo study, animals were divided into four groups. Group I (Vehicle control): animals were administered 0.9% (w/v) of normal saline (1mL/100g; p.o.). Group II (Cisplatin): animals were treated with cisplatin (2mg/kg; i.p.). Group III (Cisplatin + sitagliptin): animals were administered cisplatin along with sitagliptin. Group IV (Sitagliptin): animals were given sitagliptin (10mg/kg; p.o.). All the treatments were administered for 8 weeks. On last day of treatment, behavioral evaluations including locomotor and rotarod studies were performed. In addition, several antioxidant enzymes were also estimated from cerebellum tissues; such as levels of thiobarbituric acid reactive substance (TBARS) were determined as a marker of lipid peroxidation, reduced glutathione (GSH) and catalase (CAT) were also estimated. Histological study of cerebellum tissue was also performed after performing the behavioral study. Exposure to cisplatin decreased cell viability in PC12 cells which were significantly increased by co-treatment with sitagliptin. In in vivo study, cisplatin significantly elevated the level of TBARS and reduced the level of antioxidant enzymes such as GSH and CAT which were significantly restored in sitagliptin + cisplatin group of rats. In addition, cisplatin impaired performance on the locomotor and rotarod activities, whereas sitagliptin significantly improved the performance of both activities. These results suggested the neuroprotective influence of sitagliptin by protecting cerebellum part of brain against cisplatin-induced toxicity.

Achyranthes aspera Linn. alleviates cerebral ischemia-reperfusion-induced neurocognitive, biochemical, morphological and histological alterations in Wistar rats

Ethnopharmacological relevanceIn the traditional system of Indian medicine, the whole plant and roots of Achyranthes aspera L have been extensively used to treat neurological conditions such as epilepsy and stroke by the various ethnic communities of India. Aim of the studyThe present study was aimed to evaluate the cerebroprotective potential of methanol extract of A. aspera aerial parts (MeAA). Materials and methodsInitially the MeAA was evaluated for total phenolic content and subjected to detailed liquid chromatography–mass spectrometry analysis. Additionally, it was evaluated for in vitro antioxidant activity in ferric reducing antioxidant power, 2, 2-diphenyl-1-picrylhydrazyl and oxygen radical absorbance capacity assays. Furthermore, in RAW 264.7 cell lines the effect of MeAA was evaluated on lipopolysaccharide-induced generation of reactive oxygen species, nitrite and tumor necrosis factor-α. Finally, the MeAA (400 and 800 mg/kg) was evaluated against ischemia-reperfusion (I/R)-induced brain injury in rats. In brief, male Wistar rats were allocated in to five groups (G-I to G-V, n = 10). G-I and G-II assigned as sham control and I/R control, and received only vehicle (carboxy methyl cellulose 0.5% w/v, 10 ml/kg, p.o.). G-III received quercetin (20 mg/kg, p.o.) and assigned as reference standard. G-IV and G-V group animals received 400 and 800 mg/kg oral doses of MeAA, respectively.All the treatments were given orally for a period of seven days and the parameters such as functional (neurological, cognitive and motor), morphological (edema and infarct area), biochemical (superoxide dismutase, catalase, reduced glutathione, lipid peroxidation, cytokines), and histopathological evaluations of the brain tissue was performed. ResultsThe MeAA exhibited 72.48 mg gallic acid equivalents/g of total phenolic content and the LC-MS/MS analysis showed acteoside, apigenin, and pentagalloyl glucose as major ingredients in the MeAA. In in vitro antioxidant assays, the MeAA showed good antioxidant activity with IC50 of 126.50 μg/ml in DPPH assay; FRAP and ORAC values of 759.65 and 979.4 in FRAP and ORAC assays, respectively. Further,the MeAA significantly suppressed the generation of ROS, nitrite and TNF-α in LPS activated RAW 264.7 cell lines. Besides, sixty mins of global cerebral ischemia followed by 24 h of reperfusion produced considerable alterations in neurobehavioral functions in the I/R control group compared to sham control, with a significant reduction in catalase and superoxide dismutase enzyme activities. Moreover, there was a significant reduction in reduced glutathione levels with increased lipid peroxidation. Furthermore, the levels of pro-inflammatory cytokines (TNF-α, IL-6, and ICAM-I) increased significantly and those of anti-inflammatory (IL-10) decreased. I/R insult increased the brain volume and aggravated cerebral infarct formation. Histopathological examination of the brain tissue revealed vascular congestion, cerebral edema, leukocyte infiltration, and brain tissue necrosis. Interestingly, seven days pretreatment with MeAA (800 mg/kg, p.o.) has offered significant protection against I/R-induced functional, morphological, biochemical and histopathological alterations in Wistar rats. ConclusionsThese findings suggest that the MeAA possesses potent cerebroprotective action through its antioxidant and anti-inflammatory mechanisms.

English

This study histologically and histochemically assess the effect of ethanol fruit extract of Phoenix dactylifera L. (EFPD) on the cerebral cortex of lead acetate exposed Wistar rats. Twenty rats were grouped into five groups (A to E, n=4). Group A (control) was administered distilled water (2 ml/kg), while groups B to E were treatment groups. Cerebral damage was induced in rats by the administration of lead acetate (120 mg/kg). Groups B, C, D and E were administered lead acetate (120 mg/kg) for a period of 3 weeks, after which groups C and D were administered EFPD (500 and 1000 mg/kg, respectively) and group E was administered dimercaptosuccinic acid (10 mg/kg) for 2 weeks. All administrations were via oral route, once daily. Microscopic examination of cerebral sections of lead acetate-treated rats revealed histo-architectural alteration; cortical degenerative changes, such as, necrosis, satellitosis, vacuolation and neuronal cytoplasmic shrinkage. However, administration of EFPD remarkably ameliorated lead acetate-induced cortical cerebral degenerative changes in the rats, in a dose dependently manner, as compared to the reference drug dimercaptosuccinic acid. Results suggest that EFPD is a potential therapeutic agent against lead acetate-induced cortical cerebral alterations in Wistar rats. &nbsp; Key words: Cerebrum, lead acetate, Phoenix dactylifera L, Wistar rats.