Tissue Antioxidant Capacity Research Articles

Antioxidant and Anti-Atherogenic Activities of Essential Oils from Myrtus communis L. and Laurus nobilis L. in Rat.

Essential oils (EOs) from aromatic and medicinal plants, such as myrtle (Myrtus communis L.) and Laurel (Laurus nobilis L.), are gaining popularity as a potential ingredient in functional foods and nutraceuticals. This study aims to investigate whether the essential oils (EOs) could be effective in weight control, antioxidative and antilipidemic status of rats by affecting microbiota and its enzymes activity and whether changes in intestinal enzyme activity affect the health of rats. The intragastric application of laurel and myrtle EOs to rats for two weeks affects weight loss, reduces glycolytic activity, lipid parameters (cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) and very low-density lipoprotein cholesterol (VLDL-C)) and atherogenic indicators, leading to cardiovascular protection. Laurel EO can be an excellent candidate for the treatment of drug-induced obesity and related diseases, since it affects lipid metabolism in the liver and inhibits the enzymes responsible for the metabolism of carbohydrates into glucose in the digestive tract, leading to weight loss. In contrast, myrtle EO shows a better antioxidant capacity in most tissues, except kidneys, where it causes a pro-oxidative effect, compared to laurel EO. Myrtle EO increases the permeability and instability of the erythrocyte membrane, resulting in a loss of selectivity for the entry of toxic substances into the cell. On the other hand, myrtle EO leads to intestinal inflammation by reducing the number of probiotic bacteria and increasing Enterobacter.

Effect of Li-ESWT on Testicular Tissue and Function in Androgen-Deficient Rat Model.

Low-intensity extracorporeal shockwave therapy (Li-ESWT), as a microenergy therapy, has the effects of inhibiting oxidative stress, antiapoptosis, and tissue repair, which is increasingly applied to a variety of diseases. Our research aims to explore the protective effects of Li-ESWT in the aging rat model and its possible molecular mechanism through in vivo and in vitro experiments. In vitro, TM3 Leydig cells incubated with H2O2 were treated with Li-ESWT at 4 energy levels (0.01, 0.05, 0.1, and 0.2 mJ/mm2). In vivo, we employed an androgen-deficient rat model to simulate male aging and treated it with Li-ESWT at three different energy levels (0.01, 0.05, and 0.2 mJ/mm2). Li-ESWT increased the expression of vascular endothelial growth factor (VEGF) in TM3 cells, improved antioxidant capacity, and reduced apoptosis, with the effect being most significant at 0.05 mJ/mm2 energy level. In androgen-deficient rat model, LI-ESWT can improve sperm count, motility, and serum testosterone level, enhancing tissue antioxidant capacity and antiapoptotic ability, and the effect is most significant at 0.05 mJ/mm2 energy level. Therefore, Li-ESWT at an appropriate energy level can improve sperm count, motility, and serum testosterone levels in androgen-deficient rat models, reduce oxidative stress in the testis, and increase antioxidant capacity and antiapoptotic abilities. The mechanism of this condition might be related to the increased VEGF expression in Leydig cells by Li-ESWT.

Бенфотіамін як антиоксидант у дренажній зоні ока при поєднаному моделюванні глаукоми та діабету

During experimental glaucoma with diabetes in rabbits, in the filtering tissues of the eye, a state of oxidative stress is formed manifested by a significant decrease in the activity of antioxidant enzymes and the accumulation of products of free radical oxidation of lipids and proteins. Administration of a lipid-soluble form of vitamin B1 benfotiamine effectively reduced the manifestations of oxidative stress in the tissues of the anterior chamber of the animal eyes. This biologically active substance increased antioxidant capacity in tissues by activating antiradical protection enzymes: superoxide dismutase activity increased by 51%, catalase by 36% and glutathione peroxidase by 45% compared to the untreated animals. In addition, the processes of lipid peroxidation and oxidative destruction of protein molecules were decreased under the influence of benfotiamine. The level of malondialdehyde (MDA) was reduced by 47%, and the marker of oxidative damage to proteins of CO-groups by 35% relative to the untreated group. The results obtained may be a basis for further studies of the pharmacological substance benfotiamine in the clinic of glaucoma accompanied by diabetes, which will expand the arsenal of pathogenetically sound therapy of this serious disease.

Liposomes as Carriers for the Delivery of Efavirenz in Combination with Glutathione-An Approach to Combat Opportunistic Infections.

Human immunodeficiency virus (HIV)-infected individuals display an enhanced production of reactive oxygen species (ROS). This reduction of antioxidant capacity in host tissues has been related to the decrease in total levels of ROS scavengers such as glutathione (GSH). Prevention of opportunistic infections due to a weakened immune system is becoming a key strategy along with HIV elimination. Research in these directions is clearly warranted, especially a combination of antiretrovirals and antioxidants to ameliorate oxidative stress, improve intracellular uptake and target viral reservoirs. Hence, we aimed to formulate liposomes loaded with the antiretroviral drug efavirenz (EFA) in the presence of glutathione, as these carriers can be engineered to enhance the ability to reach the target reservoirs. The goal of the present work was to investigate the intracellular uptake of EFA-loaded liposome (with and without GSH) by human monocytic leukemia cells (THP-1 cells) and examine cell viability and ROS scavenging activity. Results obtained provided significant data as follows: (i) treatment with EFA and GSH combination could enhance the uptake and reduce cytotoxicity; (ii) encapsulation of EFA into liposomes increased its levels in the macrophages, which was further enhanced in the presence of GSH; (iii) delivery of EFA in the presence of GSH quenched the intracellular ROS, which was significantly higher when delivered via liposomes. Data revealed that a combination of EFA and GSH encompasses advantages; hence, GSH supplementation could be a safe and cost-effective treatment to slow the development of HIV infection and produce an immune-enhancing effect.

Effect of vanillic acid on pentylenetetrazole-kindled rats: Nrf2/HO-1, IGF-1 signaling pathways cross talk.

Vanillic acid (VA) exhibited antioxidant and neuroprotective properties in some neurodegenerative disorders. So, the current study examined the neuroprotective potential of VA as an antiepileptic agent in pentylenetetrazole (PTZ)-induced epileptic rats and the prospective role of Insulin like growth factor-1 (IGF-1) and nuclear factor-2 erythroid-related factor-2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in this respect. Thirty male albino rats were equally subdivided into 3 groups; (1) normal control (NC) group, (2) PTZ-group: received PTZ (50 mg/Kg, i.p. every other day) for 14 days, and (3) PTZ + VA group: received PTZ and VA (50 mg/Kg daily for 2 weeks). The seizure score and latency were evaluated after PTZ injection. Also, the markers of oxidative stress (malondialdehyde (MDA), catalase, and reduced glutathione (GSH)), histopathological examination, the expression of glial fibrillary acidic protein (GFAP) (a marker of astrocytes) IGF-1, Nrf2, and HO-1 were assessed in the brain tissues by the end of the experiment. PTZ caused significant decrease in seizure latency and significant increase in seizure score by the end of the experiment (p < 0.01). This was associated with significant increase in MDA and GFAP with significant decrease in GSH, total antioxidant capacity (TAC) and IGF-1 in brain tissues compared to normal group (p < 0.01). On the other hand, treatment with VA caused significant attenuation in PTZ-induced seizures which was associated with significant improvement in oxidative stress markers and downregulation in GFAP and upregulation of Nrf2, HO-1 and IGF-1 in CA3 hippocampal region (p < 0.01). VA showed neuroprotective and anti-epileptic effects against PTZ-induced epilepsy which probably might be due to its antioxidant properties and upregulation of Nrf2/HO-1 pathway and IGF-1.

Impact of Chronic Sodium Fluoride Toxicity on Antioxidant Capacity, Biochemical Parameters, and Histomorphology in Cardiac, Hepatic, and Renal Tissues of Wistar Rats.

The study was designed to determine the fluoride distribution after its oral exposure in drinking water and its associated impact on biochemical, antioxidant markers and histology in the liver, kidney, and heart of male Wistar rats. On 100ppm exposure, the highest accretion of fluoride occurred in the liver followed by the kidney and heart. Fluoride exposure significantly (p˂0.05) increased the plasma levels of dehydrogenase, aminotransferases, kidney injury molecule-1 (KIM-1), and other plasma renal biomarkers but decreased the levels of total plasma proteins and albumin in a dose-dependent manner. Reduction (p˂0.05) in the activities of antioxidant enzymes viz. acetylcholinesterase, arylesterase, superoxide dismutase, catalase, glutathione peroxidase, and reductase with increased levels of protein and lipid peroxidation was recorded in the liver, kidney, and heart of fluoride-administered rats. Fluoride exposure (100ppm) induced lipid peroxidation was highest in kidney (4.4 times) followed by liver (2.6 times) and heart (2.5 times) and as compared to their respective control. The percent rise in protein oxidation at 30% was almost equal in the kidney and liver but was 21.5% in the heart as compared to control. The histopathological alterations observed included congestion and hemorrhage along with degeneration and necrosis of parenchymal cells in hepato-renal tissues and myocardium, severity of which varied in a dose-dependent manner. Taken together, fluoride distribution in the liver, heart, and kidney after chronic fluoride intake correlated well with fluoride-induced hepatic and cardio-renal toxicity in a concentration-dependent manner. These results draw attention that chronic fluoride intake pose a significant health risk for human and animal residents of fluoride endemic areas.

The Influence of Hyaluronic Acid Adjunctive Therapy of Periodontitis on Salivary Markers of Oxidative Stress: Randomized, Controlled Clinical Trial.

Periodontitis is a common oral disease affecting the tooth-supporting tissues. Bacteria have been long viewed as the main causative factor in its development; however, many investigations have proved that aberrant immune and inflammatory response and the resulting misbalance between the damage caused by reactive oxygen species and the antioxidant capacity of tissues may be an underlying factor in disease progression that reduces healing potential. The objective of the current trial is to assess the outcomes of the addition of hyaluronic acid (HA) to standard non-surgical periodontal therapy (NST) on some major oxidative stress markers in saliva. HA-based gel designed for dental application was used and the measurements were taken after 3 months. HA adjunctive therapy had a significantly greater increase in markers with antioxidant properties as well as total antioxidant capacity compared to standard NST alone. Furthermore, clinically measured levels of gingival inflammation (bleeding on probing-BOP) and periodontal destruction (clinical attachment loss-CAL) were significantly correlated with these markers, and the correlation was negative. This investigation demonstrates that HA may indeed express antioxidant properties and improve the antioxidant capacity of periodontal tissues, thus improving the prognosis for the teeth and the results of periodontal therapy. Further investigations will be necessary to determine the duration of these effects over time.

Sustained Energy Deficit Following Perinatal Asphyxia: A Shift towards the Fructose-2,6-bisphosphatase (TIGAR)-Dependent Pentose Phosphate Pathway and Postnatal Development.

Labor and delivery entail a complex and sequential metabolic and physiologic cascade, culminating in most circumstances in successful childbirth, although delivery can be a risky episode if oxygen supply is interrupted, resulting in perinatal asphyxia (PA). PA causes an energy failure, leading to cell dysfunction and death if re-oxygenation is not promptly restored. PA is associated with long-term effects, challenging the ability of the brain to cope with stressors occurring along with life. We review here relevant targets responsible for metabolic cascades linked to neurodevelopmental impairments, that we have identified with a model of global PA in rats. Severe PA induces a sustained effect on redox homeostasis, increasing oxidative stress, decreasing metabolic and tissue antioxidant capacity in vulnerable brain regions, which remains weeks after the insult. Catalase activity is decreased in mesencephalon and hippocampus from PA-exposed (AS), compared to control neonates (CS), in parallel with increased cleaved caspase-3 levels, associated with decreased glutathione reductase and glutathione peroxidase activity, a shift towards the TIGAR-dependent pentose phosphate pathway, and delayed calpain-dependent cell death. The brain damage continues long after the re-oxygenation period, extending for weeks after PA, affecting neurons and glial cells, including myelination in grey and white matter. The resulting vulnerability was investigated with organotypic cultures built from AS and CS rat newborns, showing that substantia nigra TH-dopamine-positive cells from AS were more vulnerable to 1 mM of H2O2 than those from CS animals. Several therapeutic strategies are discussed, including hypothermia; N-acetylcysteine; memantine; nicotinamide, and intranasally administered mesenchymal stem cell secretomes, promising clinical translation.

Effects of dietary curcumin on growth performance, lipopolysaccharide-induced immune responses, oxidative stress and cell apoptosis in snakehead fish (Channa argus)

In the present study, we evaluated the effects of dietary curcumin (CUR) on growth performance, and lipopolysaccharide (LPS)-induced immune responses, oxidative damage, cell apoptosis, and the expression of the related genes of the NF-κB signaling pathway in snakehead fish (Channa argus). A total of 300 Channa argus (initial body weight, 9.81 ± 0.03 g) were randomly distributed into five groups (three replicates each group), fed five diets with a basal diet supplemented with CUR at 0, 100, 200, 400, 800 mg/kg for 8 weeks. After the feeding trial, fifteen fish per tank were challenged with LPS. Results showed that CUR supplementation at 200 mg/kg diet improved the growth performance of C. argus. After the LPS challenge, dietary supplementation with 200, 400, and 800 mg/kg CUR promoted serum immunity and tissue antioxidant capacity and inhibited cell apoptosis of C. argus. At the genetic level, dietary with 200, 400, and 800 mg/kg inhibited LPS-induced inflammation response via NF-κB signaling pathways. Therefore, our results indicate that optimum dietary curcumin could attenuate LPS-induced inflammation, oxidative stress, and cell apoptosis in C. argus. Furthermore, optimum dietary CUR could improve the growth performance in C. argus, and the optimum CUR requirement in diets was estimated to be 388.125 mg/kg based on the analysis of the quadratic regression of WG. This study provides a theoretical reference for promoting the healthy culture of C. argus and the scientific application of CUR in aquaculture.

Niclosamide as a Prospective Therapeutic in L-Arginine Induced Acute Pancreatitis in Rats; Concerning Autophagic p62/ NF-kB signaling pathway

Autophagic flux impairment is recently reported as a cardinal factor in acute pancreatitis (AP)pathogenesis. Niclosamide, an anthelmintic drug, has been lately proved to be a potent autophagyenhancer. The diminution of the various inflammatory factors unrestrained release via autophagyimprovement may be helpful to improve the prognosis of AP. This study spots on investigating thepotential ameliorative effect of niclosamide on autophagic flux and its consequent curative outcomeon L-arginine-induced AP in rats. Thirty male wistar rats were divided into three groups. The first oneis the control one, the second is L-arginine induced AP group, the third group is niclosamide treatedL-arginine induced AP. Serum lipase, amylase, pancreatic tissue homogenate IL6, IL1β, TNFα, NF-kB,oxidative stress biomarkers; glutathione peroxidase activity, Hydroxy-2’-Deoxy-Guanosine and totalantioxidant capacity levels were evaluated. Besides, the DNA-binding activity of nuclear erythroidrelated factor 2 (Nrf-2) was assessed using a pancreatic tissue nuclear extract. Both LC3-II subunit &amp;P62 mRNA were quantified using PCR technique. Morphometric analysis of histopathological changeswas done. The obtained data showed that niclosamide improved L-arginine induced AP as evidencedby significantly reduced serum lipase and amylase levels, which could be related to improvement ofautophagy flux impairment as evidenced by decreased levels of LC3-II and p62 expression in pancreaticcells, in addition to anti-inflammatory effect as evidenced by decreased NF-kB and proinflammatorycytokines levels, along with improving the antioxidant capacity of the pancreatic tissue. As manifestedby elevation of Nrf-2- DNA binding activity and normalization of oxidative stress biomarkers levels.These results could pave the way for niclosamide as a potential therapeutic role in acute pancreatitis.

The protective effect of metformin against testicular damage in diabetes and prostate cancer model.

Individuals with diabetes have an increased risk of breast, colorectal, pancreatic and prostate cancer. Metformin, an oral biguanide used to treat diabetes, has anti-hyperglycaemic, anti-hyperinsulinemic and antioxidant activities. The effects of metformin on testicular tissue damage in cancer and diabetic + cancer rat models were evaluated histologically, immunohistochemically and biochemically. The diabetic model was produced in Copenhagen rats using a single dose of streptozotocin (65 mg/kg), while prostate cancer was induced through subcutaneous inoculation of 2× 104 Mat-LyLu cells into the animals. At the end of the experimental period, testicular tissues with a close functional relationship to the prostate were collected. Histological evaluation found moderate to severe damage to testes following the diabetes and cancer process. Histopathological and biochemical impairments were observed in the early stage of prostate cancer, which were increased in the diabetic animals. Metformin administration reversed these injuries and provided substantial protection of the testes. In particular, metformin had protective effects on tissue damage, apoptosis, oxidative stress and antioxidant capacity. This suggests that metformin should be further investigated as a targeted protective drug against prostate cancer-related damage to the testes.

Dietary black cumin (Nigella sativa) improved hemato-biochemical, oxidative stress, gene expression, and immunological response of Nile tilapia (Oreochromis niloticus) infected by Burkholderia cepacia

The present study assessed the protective aspects of the dietary exposure to black cumin (Nigella sativa, NS) powder on immune response, liver and kidney enzymes, tissue antioxidant capacity, gene expression, and testing the antibacterial activity against Burkholderia cepacia (B. cepacia, BC). Nile tilapia (O. niloticus) (n = 150) were divided into 5 groups, the first was control (Cont) neither challenged nor treated, and fed a basal diet for 59 days. The second one received 30 g kg−1 of NS-incorporated diet and farmed for 45 days (45NS). The third (Cont-BC) and the fourth (14NS-BC) groups were fed a basal diet, while the fifth (59NS-BC) was fed NS-supplemented diet for 45 days. Then, the last three groups were intraperitoneally inoculated with 0.2 mL of virulent BC, and kept under observation for 14 days. During the observation period, Cont-BC group was continuously received a basal diet, while 14NS-BC and 59NS-BC were fed on NS-supplemented diet. Results showed that fish received NS-dietary supplement exhibited significantly (P < 0.05) elevated levels of myeloperoxidase, lysozyme, nitric oxide, superoxide dismutase, and reduced glutathione. A clear modulation was noticed in the levels of cortisol, Malondialdehyde, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, urea, and creatinine. A clear up-regulation of inflammatory cytokines encoding genes, interleukin 8 (IL-8), interleukin 10 (IL-10), interleukin 1, beta (IL-1β) and immune-related gene, immunoglobulin M (IgM), was evident in NS-enriched groups in comparison to the control. On the contrary, challenged fish with bacterium exhibited a clear decrease in immune and antioxidant (SOD, GSH) biomarkers, while a noticeable increase in hepato-renal parameters, cortisol, and MDA levels, besides gene down-regulation. Thus, we recommend the usage of NS as a nutraceutical to stimulate immunity and as an antibacterial agent in Nile tilapia owing to modulating the immune-antioxidant status, hepato-renal function, and gene expression, besides enhancing the fish survival rates post-exposure to B. cepacia.

Effects of Dietary Inclusion of Clostridium autoethanogenum Protein on the Growth Performance and Liver Health of Largemouth Bass (Micropterus salmoides)

Clostridium autoethanogenum protein (CAP) is a novel protein source for aqua-feeds. The present study aimed to investigate the effects of dietary CAP on growth performance, immunity, and liver health status of juvenile largemouth bass (Micropterus salmoides). Four isonitrogenous and isolipid experimental diets were formulated to replace 0% (D1, control), 25% (D2), 50% (D3), and 75% (D4) of fish meal by CAP. Fish (15.05 ± 0.08 g) were randomly fed one of four experimental diets for 8 weeks. The results showed that weight gain (WG), specific growth rate (SGR), feeding rate (FR), viscerosomatic index (VSI), and hepatosomatic index (HSI) of the D4 group were significantly lower than D1, D2, and D3 groups (P &amp;lt; 0.05). With the increase of substitution level, the total antioxidant capacity (T-AOC) of liver tissue was significantly decreased, while the plasma alkaline phosphatase (AKP) activity was significantly increased (P &amp;lt; 0.05). Plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were significantly higher in D3 and D4 groups than in D1 and D2 groups (P &amp;lt; 0.05). Replacing 50 or 75% fish meal by CAP significantly induced the transcription level of apoptosis-promoting genes (bcl-2-associated death protein [bad] and bcl-2-assoxicated × protein; bag [bax]), anti-apoptosis-related genes (tumor protein 53 [p53] and b-cell lymphoma-2 [bcl-2]), and the apoptotic Caenorhabditis elegans (C. elegans) death gene-3 like caspases (cysteine-aspartic proteases-3 [caspase-3], cysteine-aspartic proteases-8 [caspase-8], cysteine-aspartic proteases-9 [caspase-9], and cysteine-aspartic proteases-10 [caspase-10]) in liver, while suppressed the gene expression of the inflammatory factors [interleukin-1β (il-1β), interleukin-8 (il-8), and tumor necrosis factor, tnf ] in head kidney. At the same time, dietary inclusion of CAP elevated the protein expression of bcl-2, autophagy microtubule-associated protein light chain 3A/B (LC3A/B-I), and LC3A/B-II by inhibiting the phosphorylation of the mammalian target of rapamycin (mTOR; P &amp;lt; 0.05). Moreover, the apoptosis rate of the D3 and D4 groups was significantly increased (P &amp;lt; 0.05). Taken together, these results indicated that the optimal level of CAP-replacing fish meal should be &amp;lt;50% that has no negative effect on the growth performance and liver health of juvenile largemouth bass. In addition, excessive CAP inclusion may damage liver health by activating autophagy and apoptosis signaling pathways.

Effects of remifentanil and propofol on distant organ lung injury in an ischemia-reperfusion model.

Our aim was to evaluate lung injury due to oxidative stress and antioxidant activity levels in an infrarenal ischemia–reperfusion model and to compare prevention effects of single and combined use of propofol and remifentanil. In this study, a total of 40 adult Wistar Albino rats were randomly divided into five groups of eight rats as SHAM, physiological saline, intraperitoneal propofol, remifentanil, and propofol and remifentanil groups. Blood and tissue samples were obtained after 80 min of reperfusion. The malondialdehyde (MDA) level, a measure of lipid peroxidation, was measured in lung tissue samples and red blood cells; additionally, total oxidant status and total antioxidant capacity of lung tissues were measured and histopathological examination was performed. Distant organ (lung) injury developed due to lower extremity ischemia–reperfusion was created by infrarenal aortic clamping. The lipid peroxidation product MDA and total oxidant levels were increased, but there was insufficient antioxidant protection both in the lung tissues and red blood cells. While propofol prevented this injury consistent with its proposed antioxidant properties; no protective effect of remifentanil was observed. On the contrary, it showed oxidative stress increasing effect. This study concluded that the antioxidant effect of propofol was suppressed by remifentanil in the case of combined use.

Transcriptome profiling reveals differential expression of immune-related genes in gills of hybrid yellow catfish (Tachysurus fulvidraco ♀ × Pseudobagrus vachellii ♂) under hypoxic stress: Potential NLR-mediated immune response

Fish gills are the primary organ that respond to sudden changes in the dissolved oxygen (DO) level in the aquatic environment. Hypoxic stress impairs the normal function of gill tissues. However, little is known about the mechanisms of the response of yellow catfish gills to hypoxic stress. In this study, we compared transcriptomic and physiological changes in gill tissues of hybrid yellow catfish (Tachysurus fulvidraco ♀ × Pseudobagrus vachellii ♂) between a hypoxia-treated group (DO: 1.5 mg/L) and a control group (DO: 6.5 mg/L). In fish in the hypoxia-treated group, gill filaments underwent adaptive changes, and the number of vacuoles in gill tissues increased. Exposure to hypoxic conditions for 96 h resulted in increased anaerobic metabolism and decreased antioxidant and immune capacity in gill tissues. Transcriptome analyses revealed 1556 differentially expressed genes, including 316 up-regulated and 1240 down-regulated genes, between fish in the hypoxia-treated and control groups. Functional analyses indicated that the main pathway enriched with differentially expressed genes was immune response, followed by energy metabolism and signal transduction. Under hypoxic stress, the transcript levels of genes involved in the NOD-like receptor signaling pathway initially increased rapidly but then decreased over time, suggesting that the NOD-like receptor-mediated immune response plays an essential role in hypoxia tolerance and resistance in hybrid yellow catfish. Our results provide novel insights into which immune-related genes and pathways are activated under hypoxic stress, and reveal details of early adaptation of the immune response and defense mechanisms under hypoxic stress.

The Hepatoprotective Role of Balanites aegyptiaca Extract and its Nano-Formulation Against Methomyl-Induced Toxicity and Oxidative Stress in Mice via Overexpression of Nrf2

IntroductionMethomyl (MET) is a monomethyl carbamate insecticide that is widely used around the world. MET is highly toxic to humans via oral exposure and mainly affects the liver tissue. It actually induces toxicity through overproduction of Reactive Oxygen Species (ROS) leading to oxidative stress with subsequent destruction of lipids, proteins, and nucleic acids.Materials and MethodsVarious plant extracts have been primarily screened for their antioxidant activities by measuring the free radical scavenging ability. Later, the plant extract with the highest antioxidant efficacy has been further formulated into a nanosuspension and the antioxidative effect has also been investigated against MET. Additionally, liver, kidney, and heart function biomarkers, liver tissue oxidative stress parameters, and total antioxidant capacity were assessed. Moreover, RT-PCR was applied to measure the Nrf2 expression.ResultsThe antioxidant screening data showed that balanites extract (BLT, Balanites aegyptiaca) had the most potent antioxidant activity. Besides, BLT showed dose-dependent improvement in liver, heart, and kidney functions in experimental mice treated with MET. The antioxidant biomarkers in liver tissue and total antioxidant capacity were elevated as compared to the MET-treated group. Furthermore, BLT significantly ameliorated MET-induced toxicity via the induction of Nrf2 and MET hepatic clearance. This study suggests the potential use of BLT extract as a natural antioxidant for the safe management of MET-induced hepatotoxicity and oxidative stress.ConclusionsBased on the presented data in this study, it can be concluded that BLT or BLT-NS can be used as a safe drug for methomyl toxicity.

Quercus infectoria gall extract aids wound healing in a streptozocin-induced diabetic mouse model.

Quercus infectoria galls have commonly been used for different therapeutic purposes. This study was conducted to investigate the effects of topical application of an ointment prepared from Quercus infectoria gall hydroethanolic extract on open wound healing in a streptozocin-induced diabetic BALB/c mouse model. After induction of diabetes, two circular wounds (5mm) were created on the dorsum of the mice which were then divided into three groups. The mice were treated with soft yellow paraffin (control-sham group) and therapeutic doses of 5% and 10% of an ointment prepared from Quercus infectoria, respectively. To evaluate the effects of the therapeutic ointment on the wound healing process, wound area, histological parameters, mRNA levels of vascular endothelial growth factor (VEGF), Bcl-2 and p53, plasma levels of interleukin-6 (IL-6) and tumour necrosis factor (TNF)-α, and tissue antioxidant capacity were investigated. The mice (n=54) were divided into three equal groups. Wound area and concentrations of IL-6 and TNF-α were significantly decreased in both ointment-treated groups compared to the control group (p<0.05). Moreover, angiogenesis, fibroblast distribution per mm2 of wound tissue, collagen deposition, rapid re-epithelialisation, and the expression of VEGF, Bcl-2 and p53 mRNA, were significantly increased (p<0.05). The administration of the ointment reduced malondialdehyde concentration and increased total antioxidant capacity compared with the control group (p<0.05). Our study suggests that an ointment prepared from Quercus infectoria gall hydroethanolic extract accelerated open wound healing in a diabetic animal model by shortening the inflammatory phase, inducing apoptosis, up-regulating the expression of Bcl-2 and p53 mRNA, antioxidant properties and cellular proliferation.

Anti-inflammatory activity of Jasminum grandiflorum L. subsp. floribundum (Oleaceae) in inflammatory bowel disease and arthritis models

Our study has renewed interest in the genus Jasmine for the treatment of chronic inflammatory conditions. Aerial parts of Jasminum grandiflorum L. subsp. floribundum total methanolic extract (JTME) were tested for its therapeutic potential as an anti-inflammatory agent using two experimental models in rats; acetic acid (AA) induced ulcerative colitis and adjuvant induced arthritis.The administration of JTME showed anti-inflammatory activity in a dose dependent manner. JTME, 400 mg/kg was like prednisolone, 2 mg/kg p.o. (the reference drug), since it improved the tissues of the colon clinically, macro and microscopically (ulcer index), and histopathological (scoring). It reduced the intestinal expression of pro-inflammatory cytokines in the colonic mucosa; IFNγ, TNFα, IL-6, IL-1, and MPO. It also preserved tight junctions in intestinal epithelial cells by counter-regulating claudin-5 and occludin levels additionally, it had a potent antioxidant activity. The expressions of NF-κB p65, TNF-α and caspase-3 in rats administered AA (2 mL of 4% solution, once, intrarectally) were significantly increased, where the lowest expression was scored in JTME, 400 mg/kg group. In the adjuvant induced model of rheumatoid arthritis, the TJME, 400 mg/kg reduced the levels of cathepsin D, iNOS, NO, RF, CRP, CPP and elevated the total antioxidant capacity of tissues. Additionally, it maintained bones without histopathological lesions, articular cartilage damage, and inflammation of the synovial membrane and periarticular tissues, in contrast to arthritic rats. Finally, we report a new detailed study to validate the medicinal importance of Jasminum for the chronic inflammatory disorders with immune dysfunction with anti-inflammatory and antioxidant effects.

Integrating Animal Health and Stress Assessment Tools Using the Green-Lipped Mussel Perna canaliculus as a Case Study

Marine organisms are constantly exposed to stress, such as changes in seawater temperature, which may elicit biochemical, molecular, and physiological changes. In the present study, an integrative approach to evaluate stress in the green-lipped mussel Perna canaliculus exposed to control, moderate, and severe heat stress was used. Flow cytometry (FCM) was used to measure hemolymph parameters, including hemocyte concentration, viability, and reactive oxygen species (ROS) production. Spectrophotometry and a handheld electrochemical meter were used to determine the total antioxidant capacity (TAC) of hemolymph and gill tissue, and metabolomics was used to contrast specific metabolic responses among treatments. For hemolymph parameters measured using FCM, the number of nonviable hemocytes increased with the severity of heat shock. The proportion of superoxide-positive hemocytes mirrored the increase in nonviability; by contrast, the general ROS production initially increased following moderate heat shock, but then decreased after severe heat shock. Trolox-equivalent antioxidant capacity in the gill tissue and fast-acting antioxidant levels in the haemolymph showed small but significant decreases following heat shock, whereas the reciprocal pattern was seen for slow-acting and TAC in the hemolymph. Metabolomic profiles discriminated between treatments, with energy metabolism pathways appearing the most affected. The approach used in this study provides a deeper mechanistic understanding of the stress responses of organisms exposed to heat stress; however, these analytical techniques may be combined or used independently to measure stress in marine organisms in the laboratory or in the field, which can improve health assessments of wild and farmed aquatic organisms.

Synergistic Effects of Exercise Training and Vitamin D Supplementation on Mitochondrial Function of Cardiac Tissue, Antioxidant Capacity, and Tumor Growth in Breast Cancer in Bearing-4T1 Mice.

Both regular exercise training and vitamin D consumption are beneficial for patients with cancer. The study investigated the effects of interval exercise training (IET) or/and vitamin D supplementation on the gene expression involved in mitochondrial function of heart tissue, tumor size, and total antioxidant capacity (TAC) in breast cancer (BC) model mice. We assigned random 40 female NMRI mice to five equal groups (n = 8); the healthy control group (H.C), cancer control group (Ca.C), cancer with the vitamin D group (Ca.VD), cancer exercise group (Ca.Ex), and cancer exercise along with the vitamin D group (Ca.Ex.VD). Forty-eight hours after treatment, we anesthetized the animals and performed the isolation of heart tissue and blood serum for further studies. The results showed that the lowest mean body weight at the end of the treatments was related to Ca.C (p = 0.001). Vitamin D treatment alone has increased tumor volume growth by approximately 23%; in contrast, co-treatment with exercise and vitamin D inhibited tumor growth in mice (P = 0.001), compared with the cancer control (12%). TAC levels were higher in the group that received both vitamin D and exercise training (Ca.Ex.VD) than in the other treatment groups (Ca.VD and Ca.Ex) (p = 0.001). In cardiac tissue, vitamin D treatment induces an elevation significantly of the mRNA expression of Pgc1−α, Mfn-1, and Drp-1 genes (p = 0.001). The study has shown the overexpression of vitamin D in female mice, and synergistic effects of IET with vitamin D on weight loss controlling, antitumorigenesis, improvement of antioxidant defense, and the modulation of gene expression. The synergistic responses were likely by increasing mitochondrial fusion and TAC to control oxidative stress. We recommended being conducted further studies on mitochondrial dynamics and biogenesis focusing on risk factors of cardiovascular disease (CVD) in patients with BC.