Endogenous Antioxidant Activity Research Articles

Quercetin treatment increases H2O2 removal by restoration of endogenous antioxidant activity and blocks isoproterenol-induced cardiac hypertrophy.

Oxidative stress, characterized by the accumulation of reactive oxygen species (ROS), is implicated in the pathogenesis of several diseases, including cardiac hypertrophy. The flavonoid quercetin is a potent ROS scavenger, with several beneficial effects for the cardiovascular system, including antihypertrophic effects. Oxidative imbalance has been implicated in cardiac hypertrophy and heart failure. In this work, we tested whether quercetin could attenuate cardiac hypertrophy by improving redox balance and mitochondrial homeostasis. To test this hypothesis, we treated a group of mice with isoproterenol (30mg/kg/day) for 4 or 8 consecutive days. Another group received quercetin (10mg/kg/day) from day 5th of isoproterenol treatment. We carried out the following assays in cardiac tissue: measurement of cardiac hypertrophy, protein sulfhydryl, catalase, Cu/Zn and Mn-superoxide dismutase (SOD) activity, detection of H2O2, and opening of the mitochondrial permeability transition pore. The animals treated with isoproterenol for the initial 4days showed increased cardiac weight/tibia length ratio, decreased protein sulfhydryl content, compromised SOD and catalase activity, and high H2O2 levels. Quercetin was able to attenuate cardiac hypertrophy, restore protein sulfhydryl, and antioxidant activity, in addition to efficiently blocking the H2O2. We also observed that isoproterenol decreases mitochondrial SOD activity, while quercetin reverses it. Strikingly, quercetin also protects mitochondria against the opening of mitochondrial permeability transition pore. Taken together, these results suggest that quercetin is capable of reversing established isoproterenol-induced cardiac hypertrophy through the restoration of cellular redox balance and protecting mitochondria.

Gastroprotective Effect of Chinese Cabbage (Brassica oleracea L. var. pekinensis) Juice in Sprague Dawley Rats

Background: Chinese cabbage or Brassica oleracea L. var. pekinensis is an edible leafy green vegetable in the family of Brassicaceae. Ethnopharmacological studies have shown that the juice of cabbage leaves is commonly used in the treatment of gastrointestinal disorders, irritable bowel syndrome, minor cuts and wounds and mastitis. Objective: This study was aimed to examine the gastroprotective effect of Chinese cabbage (Family: Brassicaceae) juice in rats by using ethanol-induced gastric ulcer model. Methods: Thirty albino male Sprague Dawley rats (150 ± 20 g) were divided into 6 groups with five rats (n = 5) in each group. The normal control group was treated with distilled water while the positive control group was intragastrically administered with omeprazole (20 mg/kg). Cabbage juice at 500 mg/kg was given orally to three experimental groups for 1-day, 7-day and 14-day, respectively. Ethanol (70 % v/v) was orally treated to all rats one hour after the last dose treatment except the normal control group. Results: Results obtained showed that repeated consumption of cabbage juice for 7 days and 14 days exhibited an increase in accumulation mucus and in the levels of superoxide dismutase (SOD), glutathione- s-transferase (GST) and glutathione peroxidase (GSH-Px) as well as a reduction in gastric lesion area induced by ethanol compared with the ulceration control group. Conclusion: In conclusion, the gastroprotective effect of Chinese cabbage juice could be associated with its ability to increase endogenous antioxidant activities of SOD, GST and GSH-Px and mucus secretion in rat stomach.

Apical periodontitis induces changes on oxidative stress parameters and increases Na+/K+-ATPase activity in adult rats

ObjectivesEndodontic infection can cause systemic alterations. The involvement of oxidative stress (OS) and transmembrane enzymes compose the pathogenesis of various systemic diseases. However, the relation among apical periodontitis (AP), OS parameters, and Na+/K+-ATPase (NKA) pump was not reported in the literature. This study evaluated the AP influence on OS parameters and NKA activity in adult rats. MethodsAdult male Wistar rats (sixteen weeks old) were randomly assigned to two experimental groups: control (CT group; n = 8) and AP (AP group; n = 9), which was induced in the first right mandibular molar tooth. After 21 days of AP induction, mandibles were dissected for radiographic analysis. In addition, the heart, liver, pancreas, and kidney were collected for analysis of endogenous OS parameters and NKA activity. Data were analyzed by Student’s T-test. Values of p < 0.05 were considered statistically significant. ResultsAP presence increased reactive species (RS) generation only in the heart, while the other analyzed organs did not have this parameter modified. Heart and pancreas had a decreased endogenous antioxidant system (catalase activity and vitamin C levels), liver and kidney had an increased one. AP increased NKA activity in the heart, liver, and pancreas, but not in the kidney. ConclusionThe modulation of both endogenous antioxidant defense system and NKA activity in vital organs suggested that alterations in the antioxidant status and cellular electrochemical gradient may be involved in the AP pathophysiology.

Anti-inflammatory effect of stevioside abates Freund's complete adjuvant (FCA)-induced adjuvant arthritis in rats.

Adjuvant arthritis is a chronic, autoimmune and inflammatory disorder of the joints. The occurrence of disorder causes a severe damage to the connective tissue eventually leading to progressive physical disability and eventual death. The recent years of evidence suggests the anti-inflammatory properties of stevioside, a diterpene glycoside. However, the effect of stevioside against adjuvant arthritis, a chronic inflammatory disorder is not known. Hence, the present study was designed to study the effect of stevioside against Freund's complete adjuvant induced arthritis model in rats. The acute anti-inflammatory effect of stevioside also studied by employing carrageenan-induced paw oedema model in rats. The biochemical markers, haematological parameters, lipid peroxidation, myeloperoxidase activity, lipoxygenase activity, the levels of PGE2 and pro-inflammatory (TNF-α, IL-6 & IL-1β) and anti-inflammatory cytokine (IL-10) were analysed. The protein expression of NF-κB (p65) COX-2 and iNOS in paw tissues were estimated by western blotting. Stevioside treatment significantly ameliorates the adjuvant induced arthritic scoring, histological alterations, paw volume, elevation of biochemical (AST, ALT, ALP and glucose levels) and haematological (haemoglobin, differential and platelet count) parameters and restored the endogenous anti-oxidant (SOD, CAT, GSH and GST) activities. Treatment with stevioside also significantly prevented the adjuvant induced elevation of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), pro-inflammatory protein expressions (iNOS, COX-2, NF-κB (p65) and pIκB/IκB ratio), prevented the increase in myeloperoxidase activity and significantly restored the anti-inflammatory (IL-10) cytokine level in paw tissues. Collectively, our findings suggest that stevioside may serve as anti-inflammatory agent and could serve as a potential adjunct therapeutic option in treating adjuvant arthritis.

Accelerated ageing profile in inflammatory arthritis is unique and tissue compartment specific.

Rheumatoid arthritis is prevalent in more than 1% of the global population, with the highest occurrence between ages 35 and 50, which places a huge burden on the economy. Drug discovery for the prevention of this chronic disease is; therefore, a priority. It is known that subclinical progression of many chronic non-communicable diseases is exacerbated via accelerated ageing, a pro-inflammatory phenotype shift. However, rheumatoid arthritis additionally has significant humoral immune activation, inflammatory signalling-and thus the accelerated ageing profile-may differ from other chronic inflammatory diseases. The current study simulated inflammatory arthritis onset in a collagen-induced arthritis (CIA) rodent model, to characterise the redox and inflammatory profile at the onset of clinical symptoms, in different tissues, in the presence and absence of preventative antioxidant treatment. The data illustrate that an increased free radical level are evident already very early on in RA disease progression. Furthermore, oxidative stress seems to somewhat precede a significant pro-inflammatory state, perhaps due to humoral immune activation. Our data across different compartments further suggest that the compensatory increase in endogenous antioxidant activity is gradually exhausted at a different pace, with the liver showing the first signs of oxidant damage, even before significant evidence exist in circulation. The current data further suggest that preventative antioxidant intervention may have a sparing effect on endogenous antioxidant mechanisms and preserve telomere length to delay disease progression-or at least the accelerated ageing known to exacerbate RA symptoms-although it did not seem to have a significant direct effect on the autoimmune activity.

Morin attenuates STZ-induced diabetic retinopathy in experimental animals.

Diabetic retinopathy (DR) occurs in untreated diabetic patients due to the strong influence of oxidative stress. Bioflavonoids are well known for their antioxidant property. Morin, a bioflavonoid, has been demonstrated for its antioxidant as well as antidiabetic activity. Thus, this research work intended to determine the ameliorative impact of morin in DR rats using STZ-induced type 1 diabetic model. To induce type 1 diabetic in rats STZ (60 mg/kg) was administered intraperitoneally. Grouping of animals was done as described below (n = 6), where, group I – normal control, group II – diabetic control, group III – morin (25 mg/kg), group IV – morin (50 mg/kg), and group V – metformin (350 mg/kg) were used. All the animals underwent treatment for 60 days as given above. It was observed that supplementation of morin (25 and 50 mg/kg) showed a noteworthy decline in elevated serum glucose level. Moreover, decrease in the level of LPO and improved activity of endogenous antioxidants (GPx, CAT, and SOD) was observed in morin treated groups. It also notably drops the concentration of TNF-α, IL-1β, and VEGF in the tissue homogenate of the retina. Furthermore, it increased the retinal thickness and cell count in the ganglion cell layer of the retina in diabetic animals. Hence, we can conclude that morin encumbers the progression of DR in diabetic animals, which may be via antioxidant property and suppression of TNF-α, IL-1β, and VEGF.

Inhibition of the Peroxisome Proliferator-Activated Receptor gamma Coactivator 1-alpha (PGC-1α)/Sirtuin 3 (SIRT3) Pathway Aggravates Oxidative Stress After Experimental Subarachnoid Hemorrhage.

BackgroundEmerging evidence shows that Sirtuin 3 (SIRT3) can exert an antioxidative effect in various neurodegenerative diseases, but whether and how SIRT3 modulates neuronal death after subarachnoid hemorrhage (SAH) remains to be elucidated.Materia/MethodsExperimental SAH was induced in adult mice by prechiasmatic cistern injection and primary neurons by OxyHb incubation. The peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and SIRT3 protein levels were examined at different time points after SAH induction. The PGC-1α protein gene knockdown in vivo and in vitro was achieved by transfection of lentivirus (LV) vectors expressing shPGC-1α or negative control (NC). Western blot, oxidative stress index, histopathology, neurological function, and cell viability analysis was performed.ResultsResults showed that the PGC-1α/SIRT3 pathway was remarkably activated in vivo and in vitro after SAH. LV-shPGC-1α treatment significantly inhibited the activation of this pathway after SAH, accompanied by deteriorated neurologic function, aggravated oxidative stress, increased neuronal apoptosis, and enhanced cytotoxicity compared with the mice or primary neurons treated with LV-NC only.ConclusionsThe present results highlight the detrimental PGC-1α/SIRT3 pathway, involving regulation of the endogenous antioxidant activity against neuronal damage, which may provide a potential therapeutic target in SAH.

Gastroprotective effect of gallic acid against ethanol-induced gastric ulcer in rats: Involvement of the Nrf2/HO-1 signaling and anti-apoptosis role

Gallic acid (3,4,5-trihydroxybenzoic acid, GA) is a phenolic compound found in many medicinal plants traditionally used in China or patent medicine such as Feiyangchangweiyan capsule (FY capsule) for the treatment of gastrointestinal diseases for decades. However, the evidence for the gastroprotective effect of GA is deficient and the pharmacological mechanisms remain limited. The present investigation was initiated to demonstrate the gastroprotective effect and to understand potential underlying mechanism of GA on ethanol-induced gastric ulcer in rats. Gastric ulcers were induced by absolute ethanol (5 mL/kg, i.g.) in male Sprague-Dawley rats, GA (10, 30, and 50 mg/kg), FY capsule (0.4 g/kg) and 30 mg/kg Lansoprazole was administered orally. Physiological saline and lansoprazole were used as negative and positive control, respectively. Induction of rats with ethanol resulted in a significant rise in ulcer index, serum levels of inflammatory cytokines markers (IL-1β, IL-6 and TNF-α), TBARS, protein expression of Bax and Caspase-3 and a significant reduction in the activities or levels of endogenous antioxidants (SOD, CAT and GSH), gastric mucosal protective factors (PGE2 and NO) and protein expression of Bcl-2. Pretreatment with GA showed a remarkable decrease in ulcer index, inflammatory cytokines markers, TBARS, protein expression of Bax and Caspase-3 and a significant increase in the activities of endogenous antioxidants, levels of PGE2 and NO, and protein expression of Bcl-2, Nrf2 and HO-1 when compared with ethanol treated groups. This study demonstrated the gastroprotective effect of Gallic acid and FY capsule on ethanol-induced gastric ulcer in rats. The underlying mechanism of GA and FY capsule against gastric ulcer in rats caused by ethanol might be involved in Nrf2/HO-1 anti-oxidative pathway and ultimately played an anti-apoptotic role through regulating Bax, Bcl-2 and Caspase-3.

Methionine augments endogenous antioxidant capacity of rice protein through stimulating MSR antioxidant system and activating Nrf2-ARE pathway in growing and adult rats

To elucidate the influence of methionine on the endogenous antioxidant activity of rice protein (RP), growing and adult rats were fed with RP and methionine-supplemented RP (RM). After 2 weeks feeding, hepatic contents of ROS were significantly reduced by RP and RM. The endogenous antioxidant responses were induced by RP and increased by RM, in which methionine sulfoxide reductases (MsrA, MsrB2, MsrB3) expression and glutathione synthesis were uniformly stimulated and up-regulated with increasing consumption of methionine. With the intake of RP and RM, Nrf2 was activated through depressing Keap1 and Cul3, resulting in the up-regulation of antioxidant-responsive element (ARE)-driven antioxidant expressions (GCLC, GCLM, CAT, SOD, HO-1, NQO1) with increasing dietary level of methionine. The present study demonstrates that methionine can augment the endogenous antioxidant activity of rice protein, which is primarily attributed to stimulating methionine sulfoxide reductases expression and enhancing glutathione synthesis via Nrf2-ARE pathway. Results suggest that the methionine availability might play a key role in inducing and augmenting the endogenous antioxidant response exerted by rice protein, which is independent of age.

Organic selenium supplement partially alleviated diquat-induced oxidative insults and hepatic metabolic stress in nursery pigs.

The study investigated antioxidant effects of Se on resilience to diquat-induced oxidative stress in nursery pigs. Thirty-five weaned pigs were individually housed and randomly assigned to one of the five treatments. Pigs were (1) fed a basal diet and intraperitoneally injected with sterile saline (negative control), (2) fed the basal diet and injected with diquat solution (positive control, PC), or fed the basal diet supplemented with 0·3 mg Se/kg as (3) sodium selenite (SS), (4) soyabean protein-chelated Se (SC) or (5) selenised yeast (SY) and intraperitoneally injected with diquat. Pigs were fed the experimental diets for 17 d and injected with diquat at 10 mg/kg body weight or saline on the 11th day of the study (day 0 post-injection (PI)). Diquat exposure induced acute stress and innate immune activation (P < 0·05) at 6 h PI and compromised (P < 0·05) plasma glutathione peroxidase activity on day 2 PI, which was accompanied by an increase in plasma malondialdehyde at 6 h and day 2 PI (P < 0·10). Organic Se, particularly SY, enhanced (P < 0·05) endogenous antioxidant activity in various aspects compared with the PC group. The growth rate and feed intake from day 0 to day 7 PI were significantly lower in the PC, SS and SC groups than the NC group (P < 0·05). Untargeted metabolomics analysis revealed that twenty-two hepatic metabolites (false discovery rate < 0·15) associated with lipid and cellular antioxidant metabolism were altered by diquat. SY restored hepatic metabolic profiles in some but not all samples.

Neuroprotective effects of gallic acid against neurotoxicity induced by sodium arsenite in rats

Arsenic causes a wide range of neurological complications including cognitive impairment, short-term memory and concentration problems. The present study investigated effects of gallic acid (GA) against sodium arsenite (SA)-induced neurotoxicity in rats. Thirty-five adult male rats were randomly divided into five groups. Group 1 received normal saline (2 ml/kg, P.O.) for 21 days. Group 2 received SA (10 mg/kg, P.O., for 14 days). Groups 3 and 4 received GA (10 and 30 mg/kg, P.O., respectively) for 7 consecutive days prior to SA treatment and continued up to 21 days, parallel to SA administration. Group 5 received GA (30 mg/kg, P.O.) for 21 days. The long-term memory, motor performance, locomotor activity, and behavioral parameters were evaluated. The activity of glutathione peroxidase (GPx) and the level of MDA and glutathione (GSH) were measured in hippocampus, corpus striatum, and cortex of brains of rats. Histopathological parameters were also assessed. GA significantly reversed SA-induced reduction of step-through latency, latency to fall, and crossing, rearing, and grooming activity. GA significantly decreased SA-induced increased MDA level, and decreased GSH level and GPx activity in different parts of brain. Our results suggest that GA enhances endogenous antioxidant activity contributing to the improvement of SA-induced neural and behavioral dysfunction.

A novel biscoumarin compound ameliorates cerebral ischemia reperfusion-induced mitochondrial oxidative injury via Nrf2/Keap1/ARE signaling

Some phytochemical-derived synthetic compounds have been shown to improve neurological disorders, especially in ischemic stroke. In this study, we identified a novel biscoumarin compound, known as COM 3, which had substantial antioxidant effects in neurons. Next, we found that COM 3 occupies a critical binding site between the Nrf2 and Keap1 dipolymer, impairing the inhibitory effects of Keap1 on Nrf2, both of which play central roles in increasing endogenous antioxidant activity. We verified that COM 3 could increase the survival of neurons experiencing oxygen and glucose deprivation (OGD) from 51.1% to 77.2% when exposure to 2.5 and 10 μg/mL of COM 3, respectively. In addition, the same concentrations of COM 3 could reduce brain infarct volumes by 33.8%to13.7%, respectively, while also reducing the neurobehavioral score from 3.3 to 1.4 on average in mice with a middle cerebral artery occlusion (MCAO). COM 3 reduced neuronal death from 36.5% to 13.9% and apoptosis from 35.1% to 18.2%. In addition, COM 3 could improve the neuronal mitochondrial energy metabolism after experiencing oxidative stress caused by OGD or MCAO. The present study suggests that COM 3 protects against OGD in neurons and MCAO in mice by interfering with the structure of Keap1 to activate the nuclear transcription of Nrf2, which balances endogenous redox activity and restores mitochondrial function. Hence, COM 3 might be a potential therapeutic agent for ischemic stroke in the clinic.

Vitamin E as an inhibitor of oxidative damage to goose meat storage

The vitamin E effect on the lipid peroxidation product content and the endogenous antioxidant activity (at -18 C during the different types of storage) has been studied in goose meat. The goose meat of three samples has been used for storage. Meat of control sample has been obtained from geese fed by the standard diet. The 1st meat test sample of geese differs from the control group by two times higher content of vitamin E (40 mg / kg) in their diet from the 42nd to the 63rd day. Meat of the 2nd test sample obtained from the control group of geese is processed by a vitamin E solution (calculated at 100 mcg per g of meat) immediately before storage. The shelf life of meat is 210 days. It has been established that the intensive accumulation of the secondary lipid peroxidation products begins from the 90th day in the goose meat during its storage. In the goose diet a double increase of the vitamin E has contributed a significant (by 27.6%, p ≤ 0.05) TBA-AP decrease in the first meat test sample in comparison with the control group at the end of the experiment. The addition of vitamin E to the diet of geese has contributed the stabilization of the antioxidant pool in their meat. It has been confirmed by a 1.88-fold lower level of TBA-AP upon initiation of peroxide oxidation of Fe2+ and by the higher coefficient of antioxidant activity (36.0%, p ≤ 0.05) in this sample in comparison with the control on the 210th day. At the end of the experiment, the vitamin E content is higher 41.7 % (p ≤ 0.01) in the first sample than in the control, β-carotene - 15.0 % (p ≤ 0.05), and vitamin A is at the level of the control sample. Processed goose meat with a solution of vitamin E also provides reliable inhibition of peroxidation processes during the first half of the experiment. However, at the end of the experiment the content of TBA-AP reaches the level of the corresponding control indices in the 2nd test sample of meat. From the 120th day, there has been the more intensive use of endogenous antioxidants. The antioxidant activity coefficient decreasing to the control level on the 210th day in this meat sample is its conformation. The meat of this sample differs by a higher content of β-carotene from the control sample significantly (by 13.5%, p ≤ 0.05). Thus, to obtain a prolonged antioxidant effect during low-temperature storage of meat it is more advisable to add vitamin E to the diet of geese in the pre-slaughter period. Key words: geese, meat storage, lipoperoxidation products, antioxidant activity, vitamins E, A, β-carotene.

Melatonin Improves the Fertilization Capacity of Sex-Sorted Bull Sperm by Inhibiting Apoptosis and Increasing Fertilization Capacitation via MT1.

Little information is available regarding the effect of melatonin on the quality and fertilization capability of sex-sorted bull sperm, and even less about the associated mechanism. Sex-sorted sperm from three individual bulls were washed twice in wash medium and incubated in a fertilization medium for 1.5 h, and each was supplemented with melatonin (0, 10−3 M, 10−5 M, 10−7 M, and 10−9 M). The reactive oxygen species (ROS) and endogenous antioxidant activity (glutathione peroxidase (GPx); superoxide dismutase (SOD); catalase (CAT)), apoptosis (phosphatidylserine [PS] externalization; mitochondrial membrane potential (Δψm)), acrosomal integrity events (malondialdehyde (MDA) level; acrosomal integrity), capacitation (calcium ion [Ca2+]i level; cyclic adenosine monophosphate (cAMP); capacitation level), and fertilization ability of the sperm were assessed. Melatonin receptor 1 (MT1) and 2 (MT2) expression were examined to investigate the involvement of melatonin receptors on sex-sorted bull sperm capacitation. Our results show that treatment with 10−5 M melatonin significantly decreased the ROS level and increased the GPx, SOD, and CAT activities of sex-sorted bull sperm, which inhibited PS externalization and MDA levels, and improved Δψm, acrosomal integrity, and fertilization ability. Further experiments showed that melatonin regulates sperm capacitation via MT1. These findings contribute to improving the fertilization capacity of sex-sorted bull sperm and exploring the associated mechanism.

Photoprotective Effects of Ice Plant (Mesembryanthemum crystallinum) Callus Extract on Gene Expression of Human Dermal Fibroblast Against UV Exposure

UV exposure is the principal cause of extrinsic photoaging. Antioxidant-related genes (SOD2 and CAT) and collagen-related genes (COL1A1 and TIMP1) were selected for analysis of the mRNA expression in human dermal fibroblasts (CCD-966SK) using qPCR. In this study, UVA-exposed (15 J/cm2 cells showed decrease in SOD2 , CAT (p &lt; 0 001) and COL1A1 (p &lt; 0 05) gene expression, indicating the decline of antioxidant ability and collagen formation. However, treatment with ice plant callus extract (2 mg/mL, 24 h) before UVA exposure significantly up-regulated SOD2 , CAT , COL1A1 and TIMP1 genes (p &lt; 0 01) by 9.5, 2.7, 1.7 and 3.8 times, respectively, compared with those of the control group, and by 10.2, 4.3 (p &lt; 0 001), 2.1 and 3.8 times, respectively, compared with those of the UVA (only) group. These results demonstrated that ice plant extracts affect both antioxidant- and collagen-related gene expressions, and show positive effects on endogenous antioxidant activity and skin collagen preservation.

Protective Effects of Dendropanax morbifera against Cisplatin-Induced Nephrotoxicity without Altering Chemotherapeutic Efficacy.

Use of the chemotherapeutic agent cisplatin (CDDP) in cancer patients is limited by the occurrence of acute kidney injury (AKI); however, no protective therapy is available. We aimed to investigate the renoprotective effects of Dendropanax morbifera water extract (DM) on CDDP-induced AKI. Male Sprague-Dawley rats (six animals/group) received: Vehicle (control); CDDP (6 mg/kg, intraperitoneally (i.p.); DM (25 mg/kg, oral); or DM + CDDP injection. CDDP treatment significantly increased blood urea nitrogen (BUN), serum creatinine (sCr), and pro-inflammatory cytokines (IL-6 and TNF-α), and severely damaged the kidney architecture. Urinary excretion of protein-based AKI biomarkers also increased in the CDDP-treated group. In contrast, DM ameliorated CDDP-induced AKI biomarkers. It markedly protected against CDDP-induced oxidative stress by increasing the activity of endogenous antioxidants and reducing the levels of pro-inflammatory cytokines (IL-6 and TNF-α). The protective effect of DM in the proximal tubules was evident upon histopathological examination. In a tumor xenograft model, administration of DM enhanced the chemotherapeutic activity of CDDP and exhibited renoprotective effects against CDDP-induced nephrotoxicity without altering chemotherapeutic efficacy. Our data demonstrate that DM may be an adjuvant therapy with CDDP in solid tumor patients to preserve renal function.

Rice protein reduces DNA damage by activating the p53 pathway and stimulating endogenous antioxidant response in growing and adult rats.

Reactive oxygen species (ROS) can cause DNA damage. Rice protein (RP) inhibits ROS accumulation. However, a link between the reduction of ROS-derived DNA damage and the intake of RP is far from clear. The main objective of this study is to elucidate the effects of RPs on the reduction of DNA damage in growing and adult rats. An intake of RP for 2weeks significantly reduced the hepatic accumulation of ROS and 8-hydroxydeoxyguanosine (8-OHdG) in growing and adult rats, whereas the hepatic p53 content was markedly increased by RPs. After 2weeks' feeding, the mRNA levels and protein expressions of p53, ataxia-telangiectasia mutated (ATM), and Checkpoint kinase 2 (Chk2) were up-regulated by RPs, whereas Murine Double Minute 2 (MDM2) expressions were markedly inhibited by RPs, resulting in more p53 being translocated into the nucleus. Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) was activated by RP by reducing Kelch-like ECH-associated protein 1 (Keap1), resulting in the up-regulation of antioxidant expressions of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in RP groups. Rice protein can exert an endogenous antioxidant activity to reduce ROS-derived DNA damage by activating the Nrf2-Keap1 pathway. This study suggests that the activation of the ATM-Chk2-p53 pathway might be one of the mechanisms exerted by RP for reducing DNA damage in growing and adult rats. © 2019 Society of Chemical Industry.

Pharmacological investigation of 'HIM-CHX': A herbal combination in the experimental muscle wasting condition.

Muscle wasting diseases are gradually increasing with the increase in global life expectancy. This study was designed to evaluate the efficacy of HIM-CHX, a herbal combination of Boswellia serrata, Cissus quadrangularis, and Withania somnifera, on Sarcopenia. The effects of HIM-CHX on parameters such as muscle mass, grip strength, motor coordination, gait, locomotor activity and endurance were measured in rats. In addition to this, inflammatory cytokines, myokine and growth hormone levels were also evaluated. In the first experiment, HIM-CHX was administered orally to rats at the dose of 125, 250, and 500 mg/kg body weight for 12 weeks. At the end of the treatment period, muscle mass, grip strength, motor coordination and proinflammatory cytokines were evaluated. In the second experiment, HIM-CHX was administered orally at a dose of 500 mg/kg body weight for 4 weeks and gait analysis, locomotor activity, endurance and endogenous antioxidant activity were evaluated. The animals treated with HIM-CHX showed a significant improvement in gastrocnemius muscle weight, carcass weight, gait, locomotor activity and endurance. HIM-CHX exerts its effect by reducing the levels of TNF-α, IL-6, and Myostatin while increasing the IGF-1 levels which are the typical biomarkers of muscle wasting. Furthermore, the study findings indicate that HIM-CHX has the potential to correct the pathophysiological changes associated with sarcopenia.

Role of Autophagy on Heavy Metal-Induced Renal Damage and the Protective Effects of Curcumin in Autophagy and Kidney Preservation.

Curcumin is a hydrophobic polyphenol compound extracted from the rhizome of turmeric. The protective effect of curcumin on kidney damage in multiple experimental models has been widely described. Its protective effect is mainly associated with its antioxidant and anti-inflammatory properties, as well as with mitochondrial function maintenance. On the other hand, occupational or environmental exposure to heavy metals is a serious public health problem. For a long time, heavy metals-induced nephrotoxicity was mainly associated with reactive oxygen species overproduction and loss of endogenous antioxidant activity. However, recent studies have shown that in addition to oxidative stress, heavy metals also suppress the autophagy flux, enhancing cell damage. Thus, natural compounds with the ability to modulate and restore autophagy flux represent a promising new therapeutic strategy. Furthermore, it has been reported in other renal damage models that curcumin’s nephroprotective effects are related to its ability to regulate autophagic flow. The data indicate that curcumin modulates autophagy by classic signaling pathways (suppression of protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and/or by stimulation of adenosine monophosphate-activated protein kinase (AMPK) and extracellular signal-dependent kinase (ERK) pathways). Moreover, it allows lysosomal function preservation, which is crucial for the later stage of autophagy. However, future studies of autophagy modulation by curcumin in heavy metals-induced autophagy flux impairment are still needed.

Recombinant Human Erythropoietin Restrains Oxidative Stress in Streptozotocin-induced Diabetic Rats Exposed to Renal Ischemia Reperfusion Injury

BackgroundRenal ischemia/reperfusion (I/R) injury (RI/RI) is a common complication of diabetes mellitus (DM) in surgical practice. Oxidative stress plays a crucial role in this process. Recombinant human erythropoietin (rhEPO) is usually used to treat anemia resulting from several diseases. However, the functional involvement of rhEPO in diabetic RI/RI remains unclear. The present study was intended to investigate the antioxidant role of rhEPO on RI/RI in DM rats. MethodsThe bilateral renal arteries and veins of streptozotocin-induced diabetic rats were subjected to 45 minutes of ischemia followed by 1, 6, and 24 hours of reperfusion with or without rhEPO pretreatment at the beginning of an I/R procedure. The renal tissue pathomorphology, renal function, oxidative stress, and inflammatory response were evaluated by detection of a series of indices by hematoxylin-eosin staining, commercial kits, enzyme-linked immunosorbent assay, and spectrophotofluorometry, respectively. ResultsCompared to the I/R group, renal function was significantly advanced in the erythropoietin group, whose subjects were also subjected to renal tissue injury, oxidative stress, and inflammation. ConclusionThese results suggest that rhEPO preconditioning can attenuate diabetic RI/RI through regulating endogenous antioxidant activity.