Oxidative Stress In Rat Model Research Articles

Phytochemical profiling and nephroprotective potential of ethanolic leaf extract of Polyalthia longifolia against cisplatin-induced oxidative stress in rat model

Ethnopharmacological relevanceKidney problems are becoming more common globally and are considered a major health issue in the modern world with high mortality rate. Polyalthia longifolia (Sonn.) Thwaites is a tropical ethnomedicinal plant used to treat various diseases like diabetes, hypertension and urinary disorders and possess antioxidant and anti-inflammatory properties. Aim of the studyThis study aimed to investigate the phytochemical composition of 70% ethanolic leaf extract of Polyalthia longifolia (Sonn.) Thwaites (PL) and evaluates its nephroprotective effects against cisplatin-induced nephrotoxicity in Wistar rats. Materials and methodsThe leaves of PL were extracted with 70% ethanol and performed the phytochemical profiling using Liquid Chromatography–Mass Spectrometry (LC-MS). The nephroprotective effect of PL leaf extract was evaluated at three doses (150, 300 and 600 mg/kg, p.o.) for 14 days against cisplatin toxicity (16 mg/kg, i.p., once) in male Wistar rats. Body and kidney weight indices, kidney function markers and lipid profile markers in serum, and oxidative stress markers in kidney tissue were performed along with the histopathological analysis of kidney. ResultsThe LC-MS chromatograph confirmed the presence of various phytocompounds include N-Methylhernagine (aporphine alkaloid), 4-Acetamidobutanoic acid (gamma amino acid) and choline, etc. in the PL leaf extract. Exposure of cisplatin (16 mg/kg, i.p., once only) to the animals significantly elevated the levels of kidney functional markers (i.e. serum urea, uric acid, creatinine) and the lipid markers (triglyceride and total cholesterol) in blood circulation with depletion of serum albumin which were reversed by the therapy of PL leaf extract (150, 300 and 600 mg/kg) in dose-dependent manner. The altered level of body and kidney weight in cisplatin treated group was also restored by the therapy. PL leaf extract effectively improved the antioxidant defense system of kidney at all doses by restoring the levels of tissue glutathione, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase with the dose-dependent reduction of lipid peroxidation against cisplatin-induced renal oxidative stress. The histopathological observations also showed the significant recovery in cellular morphology after PL treatment when compared to the cisplatin toxicity group. The highest dose 600 mg/kg of PL leaf extract showed more pronounced renal recovery (p < 0.001) followed by other two doses, which was similar to the silymarin treatment group (a reference drug) against nephrotoxicity. ConclusionThe results of this study revealed the nephroprotective effects of PL leaves against cisplatin-induced nephrotoxicity by reversing the level of biochemical markers and mitigating oxidative stress as well as improving the architecture of renal tissues. This renal protection by PL might be due to the synergistic effect of its phytoconstituents and antioxidant efficacy.

Punicalagin improves inflammation and oxidative stress in rat model of pelvic inflammatory disease

Pelvic inflammatory disease (PID) is one of the major public health concerns accounting for 30% of infertility and 50% of ectopic pregnancy cases due to severe inflammation and fibrosis. Punicalagin® are known to exhibit potent anti-inflammatory activity. The aim of this study was to demonstrate the anti-inflammatory and antioxidant effects of Punicalagin®, against pelvic inflammatory disease in rats. Female Sprague Dawley rats (n = 24) were divided into 6 groups (n = 4) as control, PID, prophylactic (low dose and high dose) and therapeutic group (low dose and high dose). PID model was constructed by implanting the rat cervix with mixed microbe (Escherichia Coli and Staphylococcus Aureus) solution. Prophylactic group was gavaged with 3 mg/kg (low dose) and 6 mg/kg (high dose) Punicalagin® daily starting one day before PID induction and therapeutic group was gavaged with 3 mg/kg (low dose) and 6 mg/kg (high dose) Punicalagin® daily starting 1 day after confirmation of PID model. Rats were sacrificed at the end of experiment and samples from upper genital tract were collected for ELISA, antioxidant assay and histopathological examination. According to results, obvious signs of inflammation and oxidative stress including infiltration of neutrophils and significantly raised levels of cytokines, and oxidative stress markers were observed in PID group when compared to control group. Punicalagin® significantly decreased the levels of IL-1β, catalase and lipid peroxidation in both prophylactic and therapeutic groups when compared to PID group. Punicalagin® also decreased the infiltration of leucocytes in uterus of prophylactic and therapeutic group when compared to PID group, as determined by histological examination. On basis of these results, we concluded that Punicalagin® showed anti-inflammatory and antioxidant potential in rat model of pelvic inflammatory disease and could be used as possible therapeutic agent in treatment of PID.

Sleep Deprivation-Induced Oxidative Stress in Rat Models: A Scoping Systematic Review.

Sleep deprivation is highly prevalent in the modern world, possibly reaching epidemic proportions. While multiple theories regarding the roles of sleep exist (inactivity, energy conservation, restoration, brain plasticity and antioxidant), multiple unknowns still remain regarding the proposed antioxidant roles of sleep. The existing experimental evidence is often contradicting, with studies pointing both toward and against the presence of oxidative stress after sleep deprivation. The main goals of this review were to analyze the existing experimental data regarding the relationship between sleep deprivation and oxidative stress, to attempt to further clarify multiple aspects surrounding this relationship and to identify current knowledge gaps. Systematic searches were conducted in three major online databases for experimental studies performed on rat models with oxidative stress measurements, published between 2015 and 2022. A total of 54 studies were included in the review. Most results seem to point to changes in oxidative stress parameters after sleep deprivation, further suggesting an antioxidant role of sleep. Alterations in these parameters were observed in both paradoxical and total sleep deprivation protocols and in multiple rat strains. Furthermore, the effects of sleep deprivation seem to extend beyond the central nervous system, affecting multiple other body sites in the periphery. Sleep recovery seems to be characterized by an increased variability, with the presence of both normalizations in some parameters and long-lasting changes after sleep deprivation. Surprisingly, most studies revealed the presence of a stress response following sleep deprivation. However, the origin and the impact of the stress response during sleep deprivation remain somewhat unclear. While a definitive exclusion of the influence of the sleep deprivation protocol on the stress response is not possible, the available data seem to suggest that the observed stress response may be determined by sleep deprivation itself as opposed to the experimental conditions. Due to this fact, the observed oxidative changes could be attributed directly to sleep deprivation.

Amelioration of N?-nitro-L-arginine methyl ester (L-NAME) Induced Hypertension and Cardio-renal Oxidative Stress in Rat Model by Methanol Extract of Ficus exasperata Leaf

Hypertension is a chronic cardiovascular disease and an important risk factor for many cardiovascular complications which makes affordable, effective and efficient management protocols inevitable. Ficus exaspirata is a medicinal plant with antioxidant potentials that is being used in the management of diseases in Nigeria.We, therefore, investigated the ameliorative effects of Ficus exaspirata on L-NAME induced hypertension, oxidative stress and cardio-renal complicationsForty eight male rats (Wistar strain) were used in this study, and they were randomly divided into six experimental groups with eight rats in each group. Group A served as the controls and they received distilled water only for the period of 21 days. Group B was given L-NAME only at 40 mg/kg while groups C, D and E were given a daily dose of L-NAME at 40 mg/kg and methanol leaf extract at respective doses of 100 mg/kg, 200 mg/kg and 400 mg/kg for 21 days. Group F was given a daily dose of L-NAME (40 mg/kg) + Lisinopril (0.28 mg/kg) orally for 21 days. Blood pressure measurements were recorded in conscious animals by tail cuff plethysmography. Electrocardiography was also carried out. Biochemical assays were done on the serum, cardiac and renal tissues to assess the oxidative status and antioxidant defense system.Treatment with L-NAME caused a significant (p &lt;0.05) increase in blood pressure (bp) (mmHg); systolic (160.45.5±11.19), diastolic (121.78±3.69) and mean arterial blood pressure (134.78±3.67) when compared with those of the control with systolic bp (105.89±5.21), diastolic bp (83.33±5.55) and mean arterial bp (90.78±3.34). There was increase in QT and QTc intervals. A significant (P&lt;0.05) increase was also observed in the markers of oxidative stress in the heart and renal tissues such as Hydrogen peroxide (H2O2); in group B (53.46±4.76) compared with A (42.83±4.56) and Malondealdehyde (MDA) in group B (8.66±3.55) compared with A (5.30±3.21), in cardiac tissues. There was also a decrease in antioxidant defense system such as Superoxide Dismutase (SOD) in group B (11.28±3.98) when compared with the control (26.97±10.38)Treatment with Ficus exasperata leaf extract caused a significant (P&lt;0.05) decrease in systolic bp (108.56±4.95) diastolic bp (76.89±19.41) and mean arterial bp (85.22±14.15), restoration of heart rhythm evident in QT and QTc measurements comparable to that of the control and reduction in cardio-renal markers of oxidative stress such as H2O2 (43.42±3.75) and MDA (4.04±1.61) better than that there respective lisinopril treated groups; (51.39±8.38) and (6.14±2.22). It also led to increase in SOD (24.57±10.38) comparable to that of lisinopril (20.69±6.73).The results obtained from this study showed that the leaf extract of Ficus exasperata has anti-hypertensive and cardio-renal protective properties through modulation of oxidative stress in L-NAME induced hypertension. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of Focal Cerebellar Injury on Fracture Healing and Oxidative Stress in Rat Model: An Experimental Animal Study.

To examine the effect of cerebellar damage on the process of fracture healing. A total of forty-two male rats were selected at random and subsequently allocated into three distinct groups. The experimentals were divided into two subgroups within each group, with the intention of sacrificing them during the third and sixth weeks. Group 1 had isolated femoral fracture, Group 2 had femoral fracture after craniotomy, and Group 3 had femoral fracture accompanying cerebellar injury after craniotomy. Left femoral fractures in rats in all groups were treated using an intramedullary Kirschner wire. Radiological, histological, and biochemical evaluations were conducted at 3 and 6 weeks to assess the processes of fracture healing. To determine the effects of fracture healing and cerebellar injury on oxidant-antioxidant systems, catalase (CAT), malondialdehyde, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities were measured. Between the time frame of 3 to 6 weeks, Group 3 had higher radiography scores, alkaline phosphatase levels, callus/ diaphyse ratio, callus improvement, and bone mineral density in comparison to the other groups. The activity of SOD was found to be statistically negligible in all groups, suggesting that SOD does not have a substantial impact on fracture healing in cerebellar injury. However, notable increases in the activity of GPx and CAT enzymes were observed, showing their considerable involvement in the process of fracture healing. Cerebellar injury reduces the oxidative stress in the fracture area and contributes positively to fracture healing by means of radiologically, biochemically and histopathologically.

Cardioprotection of Water Spinach (Ipomoea aquatica), Wood Apple (Limonia acidissima) and Linseed (Linum usitatissimum L.) on Doxorubicin-Induced Cardiotoxicity and Oxidative Stress in Rat Model.

The aim of this study was to investigate the pharmacological efficacy of 3 functional foods (Water spinach, Wood apple, and Linseed) against doxorubicin-induced cardiotoxicity and oxidative stress in rat models. Twenty-five Wistar Albino rats (male and female) were equally classified into 5 groups. Except for the normal control (NC) group, the animals received 2.5 mg/kg doxorubicin (DOX) intra-peritoneal injection at 48 hours intervals to create a dose of 15 mg/kg overall for 14 days. Simply a standard diet was given to the NC and DOX groups. In the 3 treatment groups such as water spinach (DOX + WS), wood apple (DOX + WA), and linseed (DOX + LS), rats were given 14 gm/day/rat fried water spinach, mashed wood apple, roasted linseed, respectively mixed with regular rat diet at 1:1 ratio. Blood and heart samples were collected by sacrificing all the rats on the last of the experiment day (the 15th day). LDH (lactate dehydrogenase), CK-MB (creatine kinase myocardial band), MDA (malondialdehyde), and SOD (superoxide dismutase) were analyzed. Additionally, histopathological analysis was conducted for final observation. The functional foods were indicated to lower the serum cardiac biomarkers (LDH and CK-MB) as well as stress marker (MDA) significantly (P < .05) and improved heart function and oxidative stress. However, the change in serum SOD level was noted as statistically insignificant (P > .05). The biochemical outcomes of the food intervention groups were supported by the histological findings found in those groups. Consuming the investigated foods containing antioxidant phytochemicals may combat cardiac toxicity and oxidative stress. Nonetheless, thorough investigations and clinical monitoring are required to understand these functional foods' mechanism of action and dose-response effects in treating cardiotoxicity and oxidative stress.

Neuroprotective effect of anethole against rotenone induced non-motor deficits and oxidative stress in rat model of Parkinson’s disease

IntroductionNon-motor symptoms (NMS) have high prevalence in patients with Parkinson’s disease (PD). These symptoms are mainly the result of increased oxidative stress and neuronal damage. In this study we investigated the possible neuroprotective effects of anethole as a potent antioxidant on rotenone-induced behavioral deficits, hippocampal neuronal death, and oxidative stress profile in rats. MethodsMale Wistar rats were administered with anethole (62.5, 125, and 250 mg/kg, i.g) concomitantly with rotenone (2 mg/kg, s.c) for 35 days. Shuttle box and novel object recognition tests were performed to determine cognitive functions, and tail flick test was used to measure pain sensitivity. The levels of BDNF, MDA, SOD, and GPx were assayed in the hippocampus. Hippocampal neuronal damage was evaluated using cresyl violet staining technique. ResultsChronic administration of rotenone induced cognitive deficit and reduced thermal pain threshold. Rotenone also decreased SOD and GPx activities, increased MDA level, and reduced the expression of BDNF in the hippocampus. In addition, hippocampal neuronal loss was increased in rotenone treated rats. Treatment with high dose of anethole (250 mg/kg) improved cognitive function and increased pain threshold in all three doses (62.5, 125, and 250 mg/kg). Despite the unchanged SOD and GPx activities, hippocampal levels of MDA was significantly decreased after high-dose anethole treatment. Moreover, High dose of anethole increased the number of surviving neurons in the hippocampus, but couldn’t increase the BDNF expression. ConclusionOur findings indicated that anethole has antioxidant and neuroprotective effects against non-motor disorders induced by rotenone toxicity.

Intrauterine exposure to oxidative stress induces caspase-1-dependent enteric nerve cell pyroptosis.

This study determined whether oxidative stress causes the developmental abnormalities of the enteric nervous system during the embryonic period. Using the test results of tissue specimens of children with Hirschsprung disease (HSCR), we established a pregnant rat model of oxidative stress and a cellular oxidative stress model to conduct related molecular, cellular, and histopathological experiments for exploration and validation. The results of the quantitative real-time polymerase chain reaction assay indicated overexpression of pyroptosis markers (NLRP3, ASC, and caspase-1) in HSCR lesions and newborn pups in the oxidative stress group (treated with D-galactose). The expression of cathepsin D was significantly decreased in intestinal tissues of newborn pups in the oxidative stress group compared to the control group. Reactive oxygen species scavengers (N-acetyl-cysteine, NAC), the caspase-1 inhibitor (VX-765), and the NLRP3 siRNA could reverse the release of LDH, decrease the number of propidium iodide stained cells, and reduce the percentage of TUNEL/caspase-3 double-positive cells in the H2O2-treated group. Oxidative stress can induce the death of enteric nerve cells by activating caspase-1-dependent pyroptosis through NLRP3 inflammasomes, which may contribute to abnormal enteric nervous system development.

Effects of melatonin and metformin in preventing lysosome-induced autophagy and oxidative stress in rat models of carcinogenesis and the impact of high-fat diet

Imbalanced glucose tolerance and insulin resistance remain important as high cancer risk factors. Metformin administration to diabetic patients may be associated with a reduced risk of malignancy. The combined effects of the hormone melatonin and metformin in oncology practice have shown positive results. The relevance of our study is to find out the role of specific biomarkers of lysosome destruction and oxidative stress data in carcinogenesis models. The present study was designed to investigate the comparative synergic effect of peroral antidiabetic metformin (MF) and pineal hormone melatonin (MEL) administered alone and in combination in two different rat’s models of mammary tumour proliferation in vivo (N-methyl-N-nitrosourea, NMU or 7,12-dimethylbenz[a]anthracene, DMBA). We have studied the processes of lysosomal destruction (alanyl aminopeptidase AAP, leucyl aminopeptidase LAP, acid phosphatase AcP, β-N-acetylglucosaminidase NAG, β-galactosidase β-GD and β-glucuronidase β-GR) caused by evaluated oxidative stress in three types of tissues (liver, heart, and spleen) in female Sprague–Dawley rats fed a high-fat diet (10% of total fat: 2.5% from lard and 7.5% from palm olein). Our results revealed an increase in the activity of the studied lysosomal enzymes and their expression in a tissue-specific manner depending on the type of chemical agent (NMU or DMBA). MANOVA tests in our study confirmed the influence of the three main factors, type of tissue, chemical impact, and chemopreventive agents, and the combinations of these factors on the lysosomal activity induced during the process of cancerogenesis. The development and induction of the carcinogenesis process in the different rat models with the high-fat diet impact were also accompanied by initiation of free-radical oxidation processes, which we studied at the initial (estimated by the level of diene conjugates) and final (TBARS products) stages of this process. The combined effects of MEL and MF for the two models of carcinogenesis at high-fat diet impact for AAP, LAP, and AcP showed a significant synergistic effect when they impact together when compared with the effects of one substance alone (either MEL or MF) in the breast cancer model experiments. Synergistic effects of limiting destructive processes of lysosomal functioning β-GD enzyme activity we obtained in experiments with MEL and MF chemoprevention for both models of carcinogenesis for three tissues. The statistical SS test allowed us to draw the following conclusions on the role of each lysosomal parameter analyzed as an integral model: NAG > AcP > β-GD > β-GR > AAP > LAP.

Probing the antioxidant potential of Juglans regia (walnut) against arthritis-induced oxidative stress in Sprague Dawley rats.

Oxidative stress is the underlying cause of various chronic diseases and can contribute to its progression. Plant-based therapeutics are effective in the prevention of various chronic diseases through the management of underlying causes. Walnuts owing to their rich phytochemistry possess antioxidative potential. In this context, the present research was designed to explore the therapeutic potential of walnut against arthritis-induced oxidative stress in rat model. Purposely, 50 Sprague Dawley rats were separated into five groups of 10 rats each. The rats were categorized as G0 (negative control), G1 (positive control), G2 (methotrexate), G3 (walnut feed), and G4 (walnut extract). Walnut feed and extract significantly reduced oxidative stress by improving the antioxidant enzymes in arthritic rats. Total oxidative stress was reduced by 41.44% and 21.52% in G3 while 52.81% and 36.76% in G4 when compared with G1 and G2 , respectively. Antioxidant enzyme levels in serum were significantly improved after the walnut-based interventions. Evidently, superoxide dismutase level improved by 74.5% in G3 and 83.40% in G4 , while catalase level increased by 51.99% in G3 and 61.34% in G4 , respectively, when compared with G1 . Liver function biomarkers, that is, ALP and AST, were decreased in G3 and G4 when compared with G1 and G2 . The histopathological examination illustrated the promising role of walnut-based interventions in conserving the structural integrity of hepatic and renal tissues. Meanwhile, gene expression analysis revealed that walnut treatments protected from oxidative damage by the downregulation of Dual-oxidases expression. Conclusively, walnut feed and extract might serve as potent antioxidant intervention with no potential side effects. PRACTICAL APPLICATIONS: The present work was aimed to evaluate the efficacy of walnut-based interventions against arthritis-induced oxidative stress. The walnut-based interventions positively modulated the antioxidant enzymes, liver, and kidney functions, while downregulating the gene associated with oxidative stress in animal model. Consequently, the current findings suggest wider applications of walnuts to avoid free radical induced damage during arthritis; however, human intervention studies may be carried out to further understand the mechanism of their bioefficacy.

PINK1 overexpression prevents forskolin-induced tau hyperphosphorylation and oxidative stress in a rat model of Alzheimer's disease.

PTEN-induced putative kinase 1 (PINK1)/parkin pathway mediates mitophagy, which is a specialized form of autophagy. Evidence shows that PINK1 can exert protective effects against stress-induced neuronal cell death. In the present study we investigated the effects of PINK1 overexpression on tau hyperphosphorylation, mitochondrial dysfunction and oxidative stress in a specific rat model of tau hyperphosphorylation. We showed that intracerebroventricular (ICV) microinjection of forskolin (FSK, 80 μmol) induced tau hyperphosphorylation in the rat brain and resulted in significant spatial working memory impairments in Y-maze test, accompanied by synaptic dysfunction (reduced expression of synaptic proteins synaptophysin and postsynaptic density protein 95), and neuronal loss in the hippocampus. Adeno-associated virus (AAV)-mediated overexpression of PINK1 prevented ICV-FSK-induced cognition defect and pathological alterations in the hippocampus, whereas PINK1-knockout significantly exacerbated ICV-FSK-induced deteriorated effects. Furthermore, we revealed that AAV-PINK1-mediated overexpression of PINK1 alleviated ICV-FSK-induced tau hyperphosphorylation by restoring the activity of PI3K/Akt/GSK3βsignaling. PINK1 overexpression reversed the abnormal changes in mitochondrial dynamics, defective mitophagy, and decreased ATP levels in the hippocampus. Moreover, PINK1 overexpression activated Nrf2 signaling, therebyincreasing the expression of antioxidant proteins and reducing oxidative damage. These results suggest that PINK1 deficiency exacerbates FSK-induced tau pathology, synaptic damage, mitochondrial dysfunction, and antioxidant system defects, which were reversed by PINK1 overexpression. Our data support a critical role of PINK1-mediated mitophagy in controlling mitochondrial quality, tau hyperphosphorylation, and oxidative stress in a rat model of Alzheimer's disease.

Ameliorative effect of Mg-Salvia Officinalis Nanoparticles against Aluminum Chloride induced oxidative stress in rat model of Alzheimer's Disease

Alzheimer’s disease (AD) which is usually referred to as Alzheimer’s is one of the popular reasons for dementia. Mg-Salvia Officinalis NPs has been known as an interesting compound with antioxidant, anti-inflammatory and cognitive properties. The possible therapeutic effect of Mg-Salvia Officinalis NPs was evaluated in Aluminum Chloride (ALCL3) induced AD. AD was induced by intraperitoneal injection of ALCL3 at a dose (100 mg/kg b. wt.) for 2 weeks. Fifty male rats were equally divided into 5 groups. Group I (Normal control): Rats received no drugs, Group II (ALCL3- induced AD): Rats injected with ALCL3 (100mg/kg b. wt./I. P) for two weeks, Group III (Mg-Salvia Officinalis NPs treated): After 14 days of ALCL3 injection, rats treated with Mg-Salvia Officinalis NPs (5mg/kg b. wt./day, orally) for four weeks. Group IV (Donepezil treated): Rats injected with ALCL3 as group II and treated with Donepezil (1mg/kg b. wt./day, orally) for four weeks. Group V (Mg-Salvia Officinalis NPs and Donepezil treated): Rats injected with ALCL3 and treated daily with Mg-Salvia Officinalis NPs and Donepezil for four weeks. The results revealed that ALCL3-induced AD rats causing significant alterations in Tau protein and acetylcholine levels in brain tissue in addition to marked elevation of serum ALT, AST activities, urea, creatinine concentrations and oxidative stress biomarkers. Treatment with Mg-Salvia Officinalis NPs to AD rats caused marked improvement effect in all previous parameters. Conclusively, Salvia Officinalis NPs treatment ameliorates oxidative stress induced by ALCL3 in rat’s model of AD and enhances antioxidant defense system, and prevent the lipid peroxidation.

Ivermectin-functionalized multiwall carbon nanotube enhanced the locomotor activity and neuropathic pain by modulating M1/M2 macrophage and decrease oxidative stress in rat model of spinal cord injury

Since the inflammation and oxidative stress is the main pathophysiological pathway of neural damage in spinal cord injury (SCI), we tried to evaluate the role of ivermectin (IVM) combined with multi-walled carbon nanotube (MWCNT) in the treatment settings of SCI and its underlying mechanism. Wistar rats with T9 vertebra laminectomy in five groups of: sham-operated, vehicle, IVM (0.1 mg/kg), IVM-MWCNT (0.1 mg/kg), and minocycline (90 mg/kg) were used. We evaluated the locomotor scaling and other behavioral tests for neuropathic pain. Also, tissue samples were obtained to evaluate the expression of M1 and M2 macrophage marker, concentration of TNF-α, IL-1β, and IL-1, and oxidative stress level to assess neuroinflammatory changes. Both IVM and IVM-MWCNT after induction of SCI significantly enhanced the experimental tasks’ outcomes, including locomotion and neuropathic tests. Also, decreasing in pro-inflammatory cytokines including TNF-α, IL-1β, and IL-1 in the spinal cord and dorsal root ganglion tissues was also notable in both IVM and IVM-MWCNT-treated groups 28 days after induction of SCI in compared to the vehicle-treated SCI group. Both IVM and IVM-MWCNT significantly decreased oxidative stress, induced by SCI, based on the results of ROS and NADPH activity. IVM-MWCNT-treated animals indicated better outcome in every previous experiment in comparison to IVM-treated animals. The effectiveness of IVM-MWCNT was similar to minocycline treatment in all experimental task (as positive control group). IVM-MWCNT might be a novel treatment in spinal cord injury, which could act through decreasing the oxidative stress and increase the polarization of M1 in comparison to M2 macrophages.

Atractylenolide III attenuates bleomycin-induced experimental pulmonary fibrosis and oxidative stress in rat model via Nrf2/NQO1/HO-1 pathway activation

Background Bleomycin (BLM) is a chemotherapy drug used to treat cancer, one of which side effects is that it can lead to pulmonary fibrosis (PF). Atractylenoide III (AtrIII), derived from the dried roots of rhizoma atractylodis of compositae, is one of the main active substances of rhizoma atractylodis. It has anti-inflammatory, anti-tumor and other effects. This study aimed to investigate whether AtrIII alleviated BLM-induced PF and oxidative stress in rats through the nuclear factor erythroid-2-related factor 2/NQO1,NAD(P)H:quinine oxidoreductase 1/Heme oxygenase-1 (Nrf2/NQO1/HO-1) pathway. Methods A BLM-induced pulmonary fibrosis model in SD rats was established. The respiratory dynamics were evaluated by using Wholebody flow-through plethysmography. Lung injury and pulmonary fibrosis were observed by Hematoxylin-eosin (HE) and Masson staining. Apoptosis was assay by Tunel assay. Inflammatory factors were detected with commercial kits. Expression of mRNAs and proteins were detected by RT-qPCR and Western blot, respectively. Results AtrIII (1.2, 2.4 mg/kg) improved the lung injury and lung function in the BLM-induced Sprague-Dawley (SD) rats. AtrIII reduced the apoptosis rate and protein expression of Caspase-3 and Caspase-9. AtrIII (1.2, 2.4 mg/kg) decrease the pulmonary fibrosis damage and protein expression transforming growth factor-β (TGF-β) and α-smooth muscle actin (α-SMA). AtrIII also down-regulated the levels of interleukin 6 (IL-6), inductible nitric oxide synthase (iNOS) and tumor necrosis factor-α (TNF-α), while up-regulated the level of IL-10 in peripheral blood serum. Moreover, AtrIII (1.2, 2.4 mg/kg) increased the activity of superoxide dismutase (SOD) and glutathione (GSH), while decreased the malondialdehyde (MDA) content and lactate dehydrogenase (LDH) activity. AtrIII (1.2, 2.4 mg/kg) increased the levels of Nrf2, NQO1 and HO-1. In addition, AtrIII reversed the effects of Nrf2 interference on pulmonary fibrosis damage, decreased SOD and GSH activity, and increased MDA content. Conclusion AtrIII could attenuate the pulmonary fibrosis and reliev oxidative stress through the Nrf2/NQO1/ HO-1 pathway.

Metformin Ameliorates Oxidative Stress Induced by Diabetes Mellitus and Hepatocellular Carcinoma in Rats.

Several studies have found an association between Diabetes mellitus (DM) and an increased risk for hepatocellular carcinoma (HCC). Evidence suggests that Metformin (Met) may have a therapeutic and protective effect against both DM and HCC. Therefore, the aim of this study was to evaluate the antioxidant effect of Met against DM and HCC-induced oxidative stress in rat model. Forty-two male albino rats were randomly divided into six groups. Group 1 (Gp1) was the control group, Gp2 received an intraperitoneal (i.p.) injection with streptozotocin (STZ), Gp3 was injected i.p. with diethyl nitrosamine (DEN), Gp4 received an oral administration of Met, Gp5 and Gp6 received the same injections as Gp2 and Gp3, respectively, then received an additional injection of Met. Oxidative stress biomarkers, including superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and malondialdehyde (MDA), were examined. Furthermore, biochemical parameters including liver function tests were assessed. Histopathological and immunohistochemical alterations of the liver were also examined. Our results demonstrate that Gp2 and Gp3 had significant signs of liver dysfunction and had elevated levels of MDA and reduced levels of SOD, CAT, and GSH. Additionally, Gp2 and Gp3 showed significant alterations in the liver architecture shown by high PCNA and caspase-3 expression. In the Gp5 and Gp6, treatment with Met showed an improvement in liver function, oxidative stress biomarkers, and reduced histopathological changes in hepatocytes. This study offers insight into the potential for Metformin as a novel therapeutic against the oxidative stress induced by DM or HCC.

Hepatoprotective effects of chamazulene against alcohol-induced liver damage by alleviation of oxidative stress in rat models.

Liver injury and disease caused by alcohol is a common complication to human health worldwide. Chamazulene is a natural proazulene with antioxidant and anti-inflammatory properties. This study aims to investigate the hepatoprotective effects of chamazulene against ethanol-induced liver injury in rat models. Adult Wistar rats were orally treated with 50% v/v ethanol (8–12 mL/kg body weight [b.w.]) for 6 weeks to induce alcoholic liver injury. Chamazulene was administered orally to rats 1 h prior to ethanol administration at the doses of 25 and 50 mg/kg b.w. for 6 weeks. Silymarin, a commercial drug for hepatoprotection, was orally administered (50 mg/kg b.w.) for the positive control group. Chamazulene significantly reduced (p < 0.05) the levels of serum alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and malondialdehyde, whereas the levels of antioxidant enzymes (glutathione peroxidase, catalase, and superoxide dismutase) and reduced glutathione were significantly restored (p < 0.05) in contrast to the ethanol model group. The levels of pro-inflammatory cytokines (tumour necrosis factor-α and interleukin-6) were suppressed by chamazulene (p < 0.05) with relevance to ethanol-induced liver injury. Histopathological alterations were convincing in the chamazulene-treated groups, which showed protective effects against alcoholic liver injury. Chamazulene has a significant hepatoprotective effect against ethanol-induced liver injury through alleviation of oxidative stress and prevention of inflammation.

Influence of Polyalthia longifolia (Sonn) leaves on oxidative stress biomarkers in the kidney of cadmium-induced toxicity rats

Polyalthia longifolia (Sonn.) (False ashoka) is well-known in traditional system of medicine for its medicinal and therapeutic uses. However, the ameliorative effect of this plant against cadmium-induced oxidative stress in rat model has not been reported. Hence, this preliminary study investigates the prophylactic and the curative effects of aqueous and methanolic leaf extracts of Polyalthia longifolia against cadmium-induced nephrotoxicity in rats. Animals in group I served as control and administered distilled water only; group II was administered cadmium (4 mg/kg/body weight) every other day for 14 days; rats of groups III and IV served as the prophylactic group and were pre-treated with P. longifolia aqueous and methanolic leaf extract for 7 days and then exposed to cadmium for 7 days; and groups V, VI, VII, and VIII served as curative groups and were firstly exposed to cadmium for 7 days and then post-treated with 100 mg and 200 mg/kg body weight of aqueous extract and 100 mg and 200 mg/kg body weight of methanolic extract P. longifolia for another 7 days. Cd intoxication significantly (p < 0.05) increased the activities of serum creatinine and C-reactive protein levels. Cd exposure caused a significant increase (p < 0.05) in tissue total cholesterol and triglyceride levels. The levels of renal antioxidant parameters: glutathione-s-transferase, superoxide dismutase, catalase, glutathione reductase, and reduced glutathione, were significantly (p < 0.05) decreased in Cd-intoxicated rats with concomitant elevation of lipid peroxidation. Histopathological examination confirms the biochemical findings. Pre- and post-treatment with P. longifolia restored antioxidant status, improved lipid profiles, and attenuated the lesions in the tissues. Both extracts of P. longifolia protects against Cd-induced kidney toxicities via antioxidant activities.

Thymoquinone attenuates oxidative stress of kidney mitochondria and exerts nephroprotective effects in oxonic acid-induced hyperuricemia rats.

Recent studies indicate hyperuricemia as an aggravating factor for kidney diseases progression. Basic research for novel agents to reduce hyperuricemia and kidney abnormalities will be highly rewarding. Herein, we report Thymoquinone (Tq) as an active constituent of Nigella sativa to have renal protective effective against oxonic acid (OA)-induced hyperuricemia, hypertension, and renal oxidative stress in rat models. OA 750 mg/kg BW for 12 weeks was used to induce uricemia in Sprague dawley rats. Tq at 10 and 20 mg/kg BW were administered along with OA for treatment groups. Plasma uric acid concentration and systolic blood pressure were measured. Oxidative stress markers, total ATP content, and membrane bound ATPases were measured in renal mitochondria. Anti-oxidant enzymes were analyzed in the renal tissues. Apoptosis in renal tissue was detected. Key signaling proteins for apoptosis, oxidative stress, and lipid oxidation pathways were determined. OA induced both circulating uric acid levels and hypertension in the control group which was brought down on Tq treatments. Tq effectively prevented accumulation of uric acid and oxidative stress in the renal tissues. Tq also proved to increase the total ATP content of the renal mitochondria and prevented the apoptosis induced by OA. Tq increased the expressions of phosphorylated Akt, Nrf2, and HO-1 proteins while decreasing the levels of cleaved caspase-3 in renal cells. In summary, Tq exhibited protective effects on hyperuricemia-mediated renal oxidative stress and mitochondrial abnormalities which could be mediated by Nrf2/HO-1, Akt signaling pathways.

Effects of Creatine Treatment on Jejunal Phenotypes in a Rat Model of Acidosis.

We investigated the effects of creatine treatment on jejunal phenotypes in a rat model of oxidative stress induced by acidosis. In particular, the activities of some antioxidant enzymes (superoxide dismutase, glutathione peroxidase, catalase, and glutathione reductase), the level of lipid peroxidation, the expression of heat shock proteins (HSP70), and the expression of the major carriers of the cells (Na+/K+-ATPase, sodium-glucose Transporter 1—SGLT1, and glucose transporter 2—GLUT2) were measured under control and chronic acidosis conditions. Creatine did not affect the activity of antioxidant enzymes in either the control or acidosis groups, except for catalase, for which the activity was reduced in both conditions. Creatine did not change the lipid peroxidation level or HSP70 expression. Finally, creatine stimulated (Na+/K+)-ATPase expression under both control and chronic acidosis conditions. Chronic acidosis caused reductions in the expression levels of GLUT2 and SGLT1. GLUT2 reduction was abolished by creatine, while the presence of creatine did not induce any strengthening effect on the expression of SGLT1 in either the control or chronic acidosis groups. These results indicate that creatine has antioxidant properties that are realized through direct interaction of the molecule with reactive oxygen species. Moreover, the administration of creatine seems to determine a functional strengthening of the tissue, making it more resistant to acidosis.

Protective effect of daidzein against streptozotocin-induced Alzheimer's disease via improving cognitive dysfunction and oxidative stress in rat model.

Oxidative stress is performing an essential role in developing Alzheimer's disease (AD), and age-related disorder and other neurodegenerative diseases. In existing research, we have aimed at investigating the daidzein (4',7-dihydroxyisoflavone) effect (10 and 20 mg/kg of body weight), as a free radical scavenger and antioxidant in streptozotocin (STZ) infused AD in rat model. Daidzein treatment led to significant improvement in intracerebroventricular-streptozotocin (ICV-STZ)-induced memory and learning impairments that was evaluated by Morris water maze test and spontaneous locomotor activity. It significantly restored the alterations in malondialdehyde, catalase, superoxide dismutase, and reduced glutathione levels. In addition, histopathological observations in cerebral cortex and hippocampal areas confirmed the neuroprotective effect of daidzein. These outcomes provide experimental proof showing preventive effect of daidzein on memory, learning dysfunction and oxidative stress in case of ICV-STZ rats. In conclusion, daidzein offers a potential treatment module for various neurodegenerative disorders with regard to mental deficits like AD.