scholarly journals Neurotoxic Assessment of Chronic Abuse of Pregabalin in Wistar Rats

Author(s):  
Neveen A. Salem ◽  
Amani M. Alsaedi ◽  
Bedor G. Alasmari ◽  
Razan Z. Almarghalani ◽  
Shahad M. Algobe ◽  
...  

Pregabalin (Lyrica) is an analog of the gamma-aminobutyric acid neurotransmitter,   approved for the treatment of epilepsy, generalized anxiety disorder, neuropathic pain, and fibromyalgia. The possibility for abuse and/or dependence on pregabalin has risen recently. Pregabalin is controlled in many countries including Saudi Arabia. However, unofficial use of this substance is also on the increase. The purpose of this study is to assess the potential neurotoxic effects associated with overdose prolonged pregabalin supplementation. Forty male Wistar rats were divided into Group (1) normal control received distilled water, Group (2) received pregabalin (150mg/kg), Group (3) received pregabalin (300 mg/kg), and Group (4) received pregabalin (600 mg/kg). pregabalin consumption in different doses resulted in significant dysregulation in neurotransmitter release, upsurge oxidative stress markers via enhancing lipid peroxidation and depleting antioxidant markers. Also, pregabalin doses evoked brain tissue inflammation through elevating TNF-α, IL-1β, and MCP-1, Moreover promoted brain tissue apoptosis by activating caspase -3 and suppressed Bcl2. Pregabalin effects on the aforementioned parameters were dose-dependent. These findings could highlight the potential neurotoxic effect of prolonged abuse of pregabalin supplementation through dysregulating brain neurochemical, inflammatory, oxidant/antioxidant, and apoptotic mediators.

Author(s):  
Nyejirime Young Wike ◽  
Mobisson Samuel Kelechi ◽  
Godspower Onyeso ◽  
Okekem Amadi ◽  
Elizabeth Eepho Krukru

Citrullus lanatus thumb (Cucurbitaceae) commonly called watermelon is widely consumed in this part of the world as food and medicine. This study was carried out to examine the effect of methanolic extract of watermelon (Citrullus lanatus) rind on prednisolone suppressed immunity in male wistar rats. A total of 20 male wistar rats weighing 150-294g were used in 4 groups with five rats each. Group 1, the control group was given distilled water and feed, Group 2 was given 200 mg/kg body weight of methanolic extract of watermelon rind, Group 3 rats were given 2.5 mg/kg body weight of prednisolone and Group 4 rats were given 2.5 mg/kg body weight of prednisolone and 200 mg/kg body weight of methanolic extract of watermelon rind. Prednisolone and the methanolic extract of watermelon rind were administered orally for a period of 30 days. Blood samples were collected by cardio puncture from the rats for white blood cell (WBC), lymphocyte, and granulocyte and monocyte counts at the end of the experiment.  The data were statistically analysed using one-way ANOVA (Analysis of variance). Data were considered significant at p<0.05. The results obtained showed that methanolic extract of watermelon rind caused a significant increasen in immune function of rats when compared with the control and immune suppressed rats.


F1000Research ◽  
2022 ◽  
Vol 10 ◽  
pp. 1161
Author(s):  
Mirasari Putri ◽  
Bening Mauliddina Rastiarsa ◽  
Raden Aliya T. M. Djajanagara ◽  
Ghaliby Ardhia Ramli ◽  
Neni Anggraeni ◽  
...  

Background: Sepsis causes several immunological and metabolic alterations that induce oxidative stress. The modulation of fatty acid-binding protein 4 (FABP4) has been shown to worsen this condition. Extract of cogon grass root (ECGR) contains flavonoids and isoeugenol compounds that exhibit anti-inflammatory and antioxidant properties. This study aimed to assess the effects of ECGR on FABP4 and oxidative stress–related factors in a sepsis mouse model. Methods: Twenty-nine male mice (Mus musculus) of the Deutsche Denken Yoken strain were divided into four groups: group 1, control; group 2, mice treated with 10 μL/kg body weight (BW) lipopolysaccharide (LPS); and groups 3 and 4, mice pre-treated with 90 and 115 mg/kg BW, respectively, and then treated with 10 μL/kg BW LPS for 14 d. Blood, liver, lymph, and cardiac tissue samples were collected and subjected to histological and complete blood examinations. Antioxidant (Glutathione peroxidase 3 (GPx3) and superoxide dismutase), FABP4 levels, and immune system-associated biomarker levels (TNF-α, IL-6 and IL-1β ) were measured. Results: Significant increases in platelet levels (p = 0.03), cardiomyocyte counts (p =0.004), and hepatocyte counts (p = 0.0004) were observed in group 4 compared with those in group 2. Conversely, compared with those in group 2, there were significant decreases in TNF-α expression in group 3 (p = 0.004), white pulp length and width in group 4 (p = 0.001), FABP4 levels in groups 3 and 4 (p = 0.015 and p = 0.012, respectively), lymphocyte counts in group 4 (p = 0.009), and monocyte counts (p = 0.000) and polymorphonuclear cell counts in the livers (p = 0.000) and hearts (p = 0.000) of groups 3 and 4. GPx3 activity was significantly higher in group 3 than in group 1 (p = 0.04). Conclusions: ECGR reduces FABP4 level and modulating oxidative stress markers in sepsis mouse model.


2012 ◽  
Vol 56 (1) ◽  
pp. 63-67
Author(s):  
Ramazan Col ◽  
Zafer Durgun

Abstract The presented study was planned to determine whether vasoactive intestinal peptide (VIP) could prevent cytokine haemostatic, haematological, and biochemical disturbances in LPS-treated rats. Adult male Wistar rats (weight range: 200-250 g) were used. The study included four groups: group 1 served as a control group (C); animals in group 2 were given intravenously 1.6 mg/100 g of LPS (E. coli, serotype 0.111:B4); in group 3, rats were injected intraperitoneally with 25 ng/kg of VIP; in group 4, the same doses of VIP and LPS were injected simultaneously. Blood samples were collected 6 h after treatments. In endotoxaemic rats, platelet count, fibrinogen, and antithrombin levels were decreased, the activated partial thromboplastin time and prothrombin time were prolonged, and leucopoenia, as well as significant changes in differential leukocyte percentage were demonstrated. In addition, LPS caused statistically significant increases in plasma TNF- , IL-6, and IL-10 levels, and AST, ALT, creatinine, cholesterol, triglyceride concentrations. However, it caused a statistically significant decrease in total protein and albumin levels when compared to control group. The results showed that during endotoxaemia, VIP had moderately therapeutic effect as an antiinflammatory agent, suppressing TNF-α and IL-6, and stimulating IL-10; however, it was not effective against the adverse effect of LPS on investigated haematological and biochemical parameters.


2021 ◽  
Vol 12 (1) ◽  
pp. 108-111
Author(s):  
Nsimah Monday Essien ◽  
Justina Nwadimma Nwangwa ◽  
Charles Cyprian Mfem ◽  
Johnbull Martins Uket ◽  
Efiok Aniekan Archibong

Solanum gilo (eggplant) is an edible vegetable whose leaf is reported to possess numerous medicinal properties due to its rich constituents. Against this backdrop, there is possibility that its consumption may have effect on haematological indices. Therefore this research sought to assess the effect of Solanum gilo leaf diet on some haemotological indices of albino wistar rats. About twenty four (24) albino wistar rats weighing between 120-150mg were randomly assigned into four groups of six animals each. Each rat was allowed to drinking water ad labitum. Control group received normal rodent chow while group 2 was fed 5% Solanum gilo diet. Group 3 was fed 10% Solanum gilo diet and group 4 received 20% Solanum gilo diet. The different diets were prepared by mixing different proportions of ground S. gilo leaves with rodent chow. Automated blood cell analyzer (Model PCE 210, Japan) was used for analysis of haematological parameters. Preliminary study on its proximate composition, showed the appreciable presence of crude fat, protein, fibre and carbohydrate. Consumption of S. gilo caused significant improvement in some blood parameters; notably packed cell volume (PCV), white blood cell (WBC) and platelet counts. Hence, eggplant is a nutritious vegetable with healing, the therapeutic and immunity properties. If exploited in human diet has the potentials of improving quality of life.


2006 ◽  
Vol 14 (4) ◽  
pp. 238-241 ◽  
Author(s):  
Juliane Guimarães de Carvalho ◽  
Rodrigo Cardoso de Oliveira ◽  
Marília Afonso Rabelo Buzalaf

OBJECTIVE: This study evaluated the use of plasma, bone surface (periosteal) and whole bone as biomarkers of chronic fluoride (F) exposure. METHODS: Forty male Wistar rats were assigned to 4 groups (n=10/gr) that differed according to the F concentration they received in the drinking water. Groups 1, 2, 3 and 4 received water containing 0 (control), 5, 15, and 50 mg F/L, respectively. The rats were killed at 120 days of age. Plasma and femur were collected and analyzed for fluoride with the ion specific electrode by the direct method or after hexamethyldisiloxane-facilitated diffusion. Data were tested for statistically significant differences by ANOVA and linear regression (p<0.05). RESULTS: Mean (± SE) plasma F concentrations ranged from 0.030 ± 0.002 to 0.187 ± 0.013 (mg/mL). The concentrations in surface and whole bone ranged from 610 ± 32 to 4,693 222; and 647 ± 22 to 3,439 ± 134 µg/g, respectively. The surface/whole F concentration ratios were 0.941, 1.414, 1.173 and 1.377, for groups 1, 2, 3 and 4 respectively. For plasma and whole bone, the difference among all groups was statistically significant, except for group 2 compared to group 1. For bone surface, all groups differed from each other except for group 2 compared to group 3. A significant positive correlation was found between bone surface and whole bone F (r²=0.94), as well as between plasma and bone surface (r²=0.71) and plasma and whole bone (r²=0.74). CONCLUSIONS: Data suggest that both bone surface and whole bone are suitable biomarkers of chronic F exposure in rats and plasma may be used as indicator of bone fluoride levels.


2019 ◽  
Vol 08 (02) ◽  
pp. 113-118
Author(s):  
Hakan AK ◽  
Iskender Samet Daltaban ◽  
Sevilay Vural

Abstract Aim In this experimental study, we aimed to investigate possible healing effects of memantine hydrochloride, an N-methyl-d-aspartate (NMDA) antagonist, with clinical, biochemical, and histopathologic methods on acute peripheral nerve injury (PNI). Material and Method Forty-eight adult Wistar albino rats were divided into four groups (n = 12). The groups were arranged as sham-operated group (group 1), acute compression model group (group 2), trauma + low-dose memantine group (group 3), and trauma + high-dose memantine group (group 4). Memantine was administered intraperitoneally for 7 days. Subjects were sacrificed after the measurement of the sciatic nerve function index (SNFI) on the eighth day. Cyclooxygenase 2 (COX-2) and tumor necrosis factor-α (TNF-α) levels were measured in nerve tissues. Histopathologic evaluation was performed by electron microscopy. Results The mean sciatic function index (SFI) scores of groups 1 to 4 were +3.27 (standard deviation [SD] ±4.66),–18.2 (SD = ±11.7),–8.5 (SD = ±7.5), and–2.5 (SD = ±9), respectively. The mean COX-2 values were 0.98 ng/mL (SD = ±0.51), 1.89 ng/mL (SD = ±0.22), 1.39 ng/mL (SD = ±0.36), and 1.35 ng/mL (SD = ±0.59), respectively. TNF-α values were 0.09 pg/mL (SD = ±0.23), 1 pg/mL (SD = ±0.96), 0.46 pg/mL (SD = ±0.55), and 0.48 pg/mL (SD = ±0.78), respectively. Group 1 showed normal histologic findings. Group 2 showed marked edema particularly in large-diameter myelins. Myelin configurations were detected in large myelinated axons in group 3. The number of mast cells in endoneurium was high in group 4. Conclusion The efficacy of memantine in the acute phase of PNI appears to be significant according to the SNFI and biochemical tests. However, histologic findings suggest that high doses of memantine have a negative effect on PNI.


Author(s):  
Vineela Sathuluri ◽  
Thakur Santh Rani

Rutin is a flavonoid of the flavonol type found in many typical plants, such as buckwheat, passion flower, apple and tea. Acrylamide (ACR) is a known industrial toxic chemical that produces neurotoxicity characterized by progressive neuronal degeneration. Rats were randomly divided into Control, ACR, Pregabalin and Rutin treated groups. Male wistar rats were treated with ACR (50 mg/kg/ i.p.) for 4 weeks which produce typical symptoms of neuropathy in rats. Pregabalin (10 mg/kg) and Rutin (50 & 100 mg/kg) were administered orally for 4 weeks after one hour of ACR administration. ACR enhanced the production of reactive oxygen species (ROS). Treatment with Rutin significantly improved neurological score. Rutinsignificantly (p<0.001) attenuated acrylamide induced oxidative stress markers. The expression of Bcl-2 was up-regulated and TNF-α, IL-6 and Bax were down-regulated by rutin treatment. From our results, it can be concluded that rutinshowed an ameliorative effect against ACR induced neurotoxicity in rats through its antioxidant, anti-inflammatory and antiapoptotic actions.


Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1391
Author(s):  
Yen-Ta Chen ◽  
Kuan-Hui Huang ◽  
John Y. Chiang ◽  
Pei-Hsun Sung ◽  
Chi-Ruei Huang ◽  
...  

This study tested the hypothesis that extracorporeal-shock-wave (ECSW) protected the functional and anatomical integrity of rat urinary-bladder against ketamine-induced damage. In in vitro study, the rat bladder smooth muscle cells (RBdSMCs) were categorized into G1 (sham-control), G2 (RBdSMCs + menadione), G3 (RBdSMCs + ECSW) and G4 (RBdSMCs + menadione + ECSW). The results showed protein expressions of oxidative-stress/mitochondrial-damaged biomarkers (NOX-1/NOX-2/oxidized protein/cytosolic-cytochrome-C/cyclophilin-D), inflammatory markers (MyD88/TRAF6/p-IKB-α/NF-κB/TNF-α/IL-6/IL-1ß/MMP-9/iNOS), and cell-stress response signalings (ASK1/p-MKK4/p-MKK7/ERK1/2//p-JNK/p-p38/p-53) were significantly increased in G2 than in G1 and G3, and those were significantly reversed in G4 (all p < 0.0001). Adult-male SD rats (n = 24) were equally categorized into group 1 (sham-control), group 2 (ketamine/30 mg/kg/daily i.p. injection for four weeks), group 3 [ketamine/30 mg/kg + ECSW/optimal energy (0.12 mJ/mm2/120 impulses/at 3 h and days 3/7/14/21/28 after ketamine administration)] and group 4 [(ketamine/30 mg/kg + ECSW/higher energy (0.16 mJ/mm2/120 impulses)] and animals were euthanized by day 42. The results showed the urine levels of pro-inflammatory cytokines (TNF-α/IL-6) were lowest in group 1, highest in group 2 and significantly higher in group 3 than in group 4 at days 1/7/14/28 (all p < 0.0001). The duration of urinary bladder contraction was lowest in group 2, highest in group 1 and significantly higher in group 4 than in group 3, whereas the maximal pressure of urinary bladder exhibited an opposite pattern of bladder contraction among the groups (all p < 0.0001). The histopathological findings of fibrosis/inflammation/keratinization and protein expressions of oxidative-stress/mitochondrial-damaged biomarkers (NOX-1/NOX-2/oxidized protein/cytosolic-cytochrome-C/cyclophilin-D), and inflammatory (TLR-2/TLR-4/MyD88/TRAF6/p-IKB-α/NF-κB/TNF-α/IL-1ß/MMP-9/iNOS) and cell-stress response (ASK1/p-MKK4/p-MKK7/ERK1/2//p-JNK/p-p38) signalings and apoptotic/fibrotic biomarkers (cleaved-caspas3/cleaved-PARB/Smad3/TFG-ß) exhibited an identical pattern of urine proinflammatory cytokine among the groups (all p < 0.0001). ECSW effectively attenuated ketamine-induced bladder damage and dysfunction.


2014 ◽  
Vol 03 (02) ◽  
pp. 107-111 ◽  
Author(s):  
J. K. Jayakumar ◽  
P. Nirmala ◽  
B.A. Praveen Kumar ◽  
Ashok P. Kumar

Abstract Background: Breast cancer is one of the most common cancers worldwide. Alarmingly, the incidence of breast cancer is rising rapidly in India. Aim: The present research was focused to assess the role of myricetin; a bioflavonoid in 7,12-dimethylbenzanthracene (DMBA)-induced breast cancer in female Wistar rats. Materials and Methods: A total of 36 female Wistar rats (total 6 groups, n = 6 per group) 6 - 8 weeks old, weighing 150 gm were used in the study. DMBA was given at the dose of 7.5 mg/kg subcutaneously in the mammary region once a week for 4 consecutive weeks in group 2. Vincristine was given in the dose of 500 μg/kg intraperitonially every week for 4 consecutive weeks in group 3. Myricetin was given orally in a dose of 50, 100, and 200 mg/kg in group 4, 5, and 6 respectively. The statistical significance of the data was determined using one way analysis of variance and Duncan’s multiple range test. Results: The result showed that myricetin increased the antioxidant levels in plasma, erythrocyte lysate, and breast tissue and was effective in preventing the oxidative damage induced by the carcinogen DMBA. Myricetin 50, 100, and 200 mg/kg/oral for 120 days treated animal resulted comparable results to that of standard vincristine and control groups. Conclusions: Myricetin was found to be either equieffective or more effective than vincristine in all the parameters studied. Myricetin proved the capacity of flavonols to act as antioxidant in cells represents a potential treatment in the field of oncology.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y C Li ◽  
F Y Lee ◽  
S Chua ◽  
H K Yip

Abstract Intracerebral hemorrhage (ICH) causes 10%-20% of all strokes and results in higher morbidity compared to other subtypes of cerebral stroke. Although early surgical intervention can clear the expanding hematoma, clinical outcomes following ICH have not significantly improved over the decades. Since ICH elicits neuroinflammation to exacerbate brain edema, damage the blood-brain barrier (BBB), lead to secondary neuronal injury, anti-inflammation may be a critical therapeutic strategy. Mesenchymal stem cell (MSC) therapy processes anti-inflammatory, immunomodulatory and tissue regenerative properties, suggesting that MSC therapy could be an effective therapy for ICH. Therefore, this study tested the hypothesis that human induced pluripotent stem cell-derived mesenchymal stem cell (iPSC-MSC) therapy could effectively reduce brain-infract volume (BIV) and improve neurological function in rat after acute ICH induced by a weight-drop device. Adult-male SD rats (n=40) were equally divided into group 1 (sham-operated control), group 2 (ICH), group 3 (ICH + hyaluronic acid (HA)/intracranial injection/3h after ICH), group 4 [ICH + HA + iPSC-MSC (1.2x106 cells/intracranial injection/3h after ICH)] and euthanized by day 28 after ICH procedure. In vitro study showed that hemorrhagic-brain tissue augmented protein expressions of inflammation (HMGB1/MyD88/TLR-4/TLR-2/NF-κB/TNF-α/iNOS/IL-1β) in cultured neurons that were significantly inhibited by iPSC-MSC treatment (all p<0.001). By days 7/14 after ICH procedure, circulating inflammatory levels of TNF-α/IL-6/MPO expressed were lowest in group 1, highest in group 2 and significantly lower in group 4 than in group 3 (all p<0.0001). By day 14 after ICH procedure, neurological function and BIV expressed an opposite pattern, whereas protein expressions of inflammation (HMGB1/MyD88/TLR-4/TLR-2/NF-κB/I-kB/TNF-α/iNOS/IL-1β/MMP-9), oxidative stress (NOX-1/NOX-2/oxidized protein) and apoptosis (mitochondrial-Bax/cleaved-caspase-2/PARP) in brain exhibited an identical pattern to circulating inflammation among the four groups (all p<0.001). Microscopy demonstrated that the number of vascular remodeling/GFAP+/53BP1+/γ-H2AX+ cells displayed an identical pattern of inflammation, whereas the NeuN+ cells displayed an opposite pattern of inflammation among the four groups (all p<0.001). In conclusion, iPSC-MSC therapy markedly reduced BIV and preserved neurological function mainly by inhibiting inflammatory/oxidative-stress generation. Acknowledgement/Funding Kaohsiung Chang Gung Memorial Hospital, Taiwan Society of Stem Cell Research


Sign in / Sign up

Export Citation Format

Share Document