Mitigation of IL-1β, IL-6, TNF-α, and markers of apoptosis by ursolic acid against cisplatin-induced oxidative stress and nephrotoxicity in rats

Background: Ursolic acid (UA) is a natural pentacyclic triterpenoid that is known for its benefits under several pathological conditions. Cisplatin (CP) is among the most preferred chemotherapeutic agents; however, its nephrotoxicity limits its clinical utility. Purpose: This study was aimed to determine the role of UA in the reduction of CP-induced nephrotoxicity and mitigation of pro-inflammatory cytokines and apoptosis in a rat model. Methodology: Male Wistar rats were randomized into vehicle control, CP (7.5 mg/kg), UA 10 mg/kg, and CP with UA 5 and 10 mg/kg groups. Kidney and blood samples were collected for assessment of renal function, measurement of pro-inflammatory cytokines, apoptosis markers, antioxidant activity, and tissue histology. Results: CP significantly increased the levels of serum Cr, BUN, and uric acid; it also induced histological damage reflecting the pathophysiology observed during nephrotoxicity. CP has also shown its pro-oxidant activity in kidney tissue because CP decreased the levels of GSH, SOD, and CAT; it increased the lipid peroxidation as measured by MDA content. In addition, CP significantly upregulated the activity of pro-inflammatory cytokines and expression of apoptotic markers, that is, there were increased levels of IL-1β, IL-6, TNF-α, caspase-3, and caspase-9. Two weeks of continuous treatment of UA showed significant recovery against CP-induced nephrotoxicity; UA decreased the levels of Cr, BUN, and uric acid and ameliorated histological damage. UA also downregulated the activities of IL-1β, IL-6, and TNF-α as well as expression of caspase-3 and caspase-9. Furthermore, CP-induced oxidative stress that was antagonized by UA—the levels of GSH, SOD, and CAT were significantly increased while MDA content was decreased. Conclusions: UA has a protective effect against CP-induced nephrotoxicity, which may be due to its antioxidant activity and mitigation of ILβ-1, ILβ-6, TNF-α, and markers of apoptosis.

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β-arrestin-2 up-regulates toll-like receptor 2 signaling and inhibits apoptosis in human endometrial cancer heterotransplants in nude mice

BMC Cancer ◽

10.1186/s12885-019-6254-4 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 2

Author(s):

Fanling Hong ◽

Yujun Zhang ◽

Wenjin Cheng ◽

Xiuli Sun ◽

Jianliu Wang

Keyword(s):

Inflammatory Cytokines ◽

Nude Mice ◽

Caspase 3 ◽

Glycogen Synthase ◽

Inflammatory Factors ◽

Toll Like Receptor ◽

Caspase 9 ◽

Serine Threonine Kinase ◽

Tnf Α ◽

Toll Like Receptor 2

Abstract Background β-arrestin-2(Arr2) functions as an anti-apoptotic factor and affects cell proliferation, but its downstream molecular pathway in endometrial carcinoma (EC) is still unclear. This study aimed to investigate the effects of the stable overexpression of Arr2 on the proliferation and apoptosis of human EC heterotransplants and the expression of associated molecules, including Toll-like receptor 2(TLR2), serine-threonine kinase Akt (Akt), glycogen synthase kinase-3β(GSK3β) and some typical inflammatory cytokines such as NF-κB p56, TNF-α and IL-6 & IL-8. Methods Human EC cell line Ishikawa, stably transfected with Arr2 full-length plasmid, was injected subcutaneously into nude mice. They were treated with 0, 10, 20 mg/kg paclitaxel and the volume and weight of the tumor tissue were measured and calculated. The necrotic index were assessed by H&E staining and microscopic observation. The levels of caspase-3, caspase-9, TLR2, NF-κB p56, Akt, GSK3β were measured by western blot, and the levels of TNF-α, IL-6, IL-8 were measured by real-time PCR. Results We found that Arr2 overexpression promoted the growth of human EC heterotransplants. Arr2 attenuated the promotion of caspase-3 and caspase-9 by paclitaxel and mediated the increase of TLR2 and several inflammatory cytokines. The levels of Akt and GSK3β were not affected. Conclusion Arr2 overexpression was associated with the increase of TLR2 and several inflammatory factors, meanwhile inhibited paclitaxel-induced anti-tumor effect on human EC heterotransplants.

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MiR-24-3p Attenuates IL-1β-Induced Chondrocyte Injury Associated With Osteoarthritis by Targeting BCL2L12

10.21203/rs.3.rs-76065/v1 ◽

2020 ◽

Author(s):

Jin Xu ◽

Xiaozhong Qian ◽

Ren Ding

Keyword(s):

Cell Viability ◽

Inflammatory Cytokines ◽

Caspase 3 ◽

Degenerative Joint Disease ◽

Joint Disease ◽

Luciferase Reporter ◽

Pcr Analysis ◽

Protective Effects ◽

Tnf Α ◽

Pro Inflammatory Cytokines

Abstract Background: Osteoarthritis (OA) is a chronic and degenerative joint disease prevalent in the elderly. MiR-24-3p has been reported to be involved in an OA-resembling environment. However, the functional role and underlying mechanism of miR-24-3p in chondrocyte injury associated with OA remains unknown. Methods: The expression of miR-24-3p was determined in OA cases and control patients, as well as IL-1β-stimulated chondrocyte cell line CHON-001 using reverse transcription quantitative PCR analysis. Cell viability was analyzed by CCK-8 assay. Apoptosis status was assessed by caspase-3 activity detection. The pro-inflammatory cytokines (TNF-α and IL-18) were determined using ELISA assay. The association between miR-24-3p and BCL2L12 was confirmed by luciferase reporter assay.Results: We first observed that miR-24-3p expression level was lower in the OA cases than in the control patients and IL-1β decreased the expression of miR-24-3p in the chondrocyte CHON-001. Functionally, overexpression of miR-24-3p significantly attenuated IL-1β-induced chondrocyte injury, as reflected by increased cell viability, decreased caspase-3 activity, pro-inflammatory cytokines (TNF-α and IL-18). Western blot analysis showed that overexpression of miR-24-3p weakened IL-1β-induced cartilage degradation, as reflected by reduction of MMP13 (Matrix Metalloproteinase-13) and ADAMTS5 (A Disintegrin And Metalloproteinase with Thrombospondin Motifs-5) protein expression, as well as markedly elevation of COL2A1 (collagen type II). Importantly, BCL2L12 was demonstrated to be a target of miR-24-3p. BCL2L12 knockdown imitated, while overexpression significantly abrogated the protective effects of miR-24-3p against IL-1β-induced chondrocyte injury.Conclusions: In conclusion, our work provides important insight into targeting miR-24-3p/BCL2L12 axis in OA therapy.

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Nobiletin Protects Against Diabetes-induced Testicular Injury via Hypophysis-gonadal Axis Up-regulation and Amelioration of Oxidative Stress

10.21203/rs.3.rs-814954/v1 ◽

2021 ◽

Author(s):

Marwa Salah ◽

Khadiga Ahmed Ismail ◽

sally mostafa khadrawy

Keyword(s):

Oxidative Stress ◽

Inflammatory Cytokines ◽

Caspase 3 ◽

Androgen Receptors ◽

Glycosylated Hemoglobin ◽

Diabetic Rats ◽

Diabetic Group ◽

High Dose ◽

Testicular Injury ◽

Pro Inflammatory Cytokines

Abstract Background: Testicular injury is one of the most serious problems of Diabetes mellitus. The present study aims to compare the effect of two different doses of nobiletin and the probable mechanisms against diabetes-induced testicular impairment in rats. Methods and Results: Streptozotocin injection was used to induce diabetes. Diabetic rats received nobiletin (10 mg/kg) or (25 mg/kg) daily and orally for 30 days. Diabetic rats displayed a significant elevation in glucose, glycosylated hemoglobin (HbA1c), homeostasis model of insulin resistance (HOMA-IR), and pro-inflammatory cytokines. Levels of serum insulin, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were significantly reduced. Histological changes with positive caspase-3 and decreased Androgen receptors (AR) immunoexpressions were observed in diabetic rats. Both doses of nobiletin improved hyperglycemia, reduced pro-inflammatory cytokines, and augmented insulin, testosterone, LH, and FSH levels. Gene and protein manifestation of LH and FSH receptors and cytochrome P450 17 α-hydroxylase (CYP17A1) was markedly down-regulated in testicular tissues of diabetic group, an effect which was markedly increased with both doses of nobiletin. In addition, both doses significantly reduced lipid peroxidation, and caspase-3 immuno-expression and improved the activity of the antioxidant enzymes and AR in testicular tissues of diabetic group. Conclusion: Both doses showed protective effects against diabetes-induced testicular injury by diminution of oxidative stress, hyperglycemia, inflammation, caspase-3 and up-regulation of the hypophysis-gonadal axis and androgen receptors. The high dose of nobiletin was more effective than the lower dose.

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Luzindole attenuates LPS/d-galactosamine-induced acute hepatitis in mice

Innate Immunity ◽

10.1177/1753425919890912 ◽

2019 ◽

Vol 26 (4) ◽

pp. 319-327 ◽

Cited By ~ 1

Author(s):

Yisheng Luo ◽

Yongqiang Yang ◽

Yi Shen ◽

Longjiang Li ◽

Jiayi Huang ◽

...

Keyword(s):

Acute Hepatitis ◽

Caspase 3 ◽

Acute Liver Injury ◽

Melatonin Receptor ◽

Potential Value ◽

Histological Damage ◽

Tnf Α ◽

Cumulative Evidence ◽

Pleiotropic Regulator ◽

Pro Inflammatory Cytokines

Melatonin is a well-documented hormone that plays central roles in the regulation of sleep–wake cycles. There is cumulative evidence to suggest that melatonin is also a pleiotropic regulator of inflammation, and luzindole has been widely used as a melatonin receptor antagonist. This study investigated the potential effects of luzindole on LPS/d-galactosamine (d-GalN)-induced acute hepatitis. The results indicated that treatment with luzindole alleviated histological damage in the liver, reduced the level of transaminases in plasma and improved the survival of LPS/d-GalN-exposed mice. Treatment with luzindole also suppressed the production of the pro-inflammatory cytokines TNF-α and IL-6 in LPS/d-GalN-exposed mice. In addition, treatment with luzindole inhibited the activation of caspase-3, -8 and -9, and suppressed the cleavage of caspase-3 and poly(ADP-ribose) polymerase. Therefore, treatment with luzindole attenuates LPS/d-GalN-induced acute liver injury, suggesting that luzindole might have potential value for the intervention of inflammation-based hepatic disorders.

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Pharmacological activation of GPR55 improved cognitive impairment, neuroinflammation, oxidative stress and apoptosis induced by lipopolysaccharide in mice

10.21203/rs.3.rs-87517/v1 ◽

2020 ◽

Author(s):

Xin Wang ◽

Xiao Tong Xiang ◽

Jie Hu ◽

Yu Mei Wu ◽

YueYue Li ◽

...

Keyword(s):

Oxidative Stress ◽

Superoxide Dismutase ◽

Inflammatory Cytokines ◽

Neuronal Apoptosis ◽

Caspase 3 ◽

Tunel Staining ◽

Sod Activity ◽

Neuroprotective Effects ◽

Impaired Performance ◽

Pro Inflammatory Cytokines

Abstract BackgroundNeuroinflammation, oxidative stress and apoptosis are implicated in the pathogenesis of Alzheimer’s disease (AD). The purpose of the present study was to investigate the neuroprotective effects and possible mechanism of G-protein coupled receptor 55 (GPR55) agonist, O-1602, on lipopolysaccharide (LPS)-induced cognitive deficits in mice. MethodsICR mice were treated with intracerebroventricular (i.c.v.) injection of LPS. Cognitive tests were performed, including the open field, Morris water maze, novel object recognition, and passive avoidance tests. The expression of GPR55, NF-κB p65, caspase-3, Bax and Bcl-2 were examined in the hippocampus by western blotting. Pro-inflammatory cytokines and microglia were detected by ELISA kit and immunohistochemical analyses, respectively. The malondialdehyde (MDA) level, and superoxide dismutase (SOD) activity were examined by assay kits. Furthermore, TUNEL-staining was used to detect neuronal apoptosis.ResultsI.c.v. injection of LPS exhibited impaired performance in the behavior tests, which were ameliorated by O-1602 treatment(2.0 or 4.0 μg/mouse, i.c.v.). Importantly, O-1602 reversed GPR55 down-regulation, decreased the expression of NF-κB p65, and suppressed the accumulation of pro-inflammatory cytokines and microglia activation, decreased malondialdehyde (MDA) level, and increased superoxide dismutase (SOD) activity. In addition, O-1602 also significantly decreased Bax and increased Bcl-2 expression as well as decreased caspase-3 activity and TUNEL-positive cells, suppressed neuronal apoptosis in the hippocampus of LPS-treated mice.Conclusionswe conclude that O-1602 may ameliorate LPS-induced cognition deficits via inhibiting neuroinflammation, oxidative stress and apoptosis mediated by NF-κB signaling in mice.

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MiR-200a-3p Accelerated Hypoxia/Reoxygenation Injury in HCM Cells by Enhancing IGF2R via Wnt/β-catenin Signalling Pathway

International Journal of Human Genetics ◽

10.31901/24566330.2021/21.02.783 ◽

2021 ◽

Vol 21 (02) ◽

Author(s):

Yaolei Ge

Keyword(s):

Cell Viability ◽

Inflammatory Cytokines ◽

Caspase 3 ◽

Signalling Pathway ◽

Dependent Manner ◽

Tnf Α ◽

Reoxygenation Injury ◽

Pro Inflammatory Cytokines ◽

Hypoxia Reoxygenation

ABSTRACT The present study examined functions of miR-200a-3p accelerated progressions of HCM cells via IGF2R and Wnt/β-catenin signalling pathway after hypoxia/reoxygenation treatment in vitro. CCK-8 showed that cell viability of HCM was inhibited while apoptosis rates detected by flow cytometry were promoted in a time dependent manner after H/R (12 hours and 24 hours). Beyond that, Bcl-2 and c-IAP1 were decreased but Bax and caspase-3 were upregulated by H/R treatment. IL-1β, IL-6, TNF-α and NLRP3 were also increased after treatment. RT-qPCR showed increased expressions of miR-200a-3p by H/R treatment while its inhibitor elevated cell viability but depressed apoptosis rate and pro-inflammatory cytokines’ expressions. IGF2R was upregulated after H/R treatment and its downregulation magnified effects of suppressed miR-200a-3p. HIF-1α/Wnt/β -catenin signalling pathway was activated by miR-200a-3p and IGF2R while IWP-2 treatment abolished the activation of Wnt3a andβ -catenin, causing decreased apoptosis and pro-inflammatory cytokines’ expressions but accelerated the cell viability.

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The Influence of Sevelamer Hydrochloride and Calcium Carbonate on Markers of Inflammation and Oxidative Stress in Hemodialysis at Six Months of Follow-Up

Frontiers in Medicine ◽

10.3389/fmed.2021.714205 ◽

2021 ◽

Vol 8 ◽

Author(s):

Elodia Nataly Díaz-De la Cruz ◽

José Ignacio Cerrillos-Gutiérrez ◽

Andrés García-Sánchez ◽

Carlos Gerardo Prado-Nevárez ◽

Jorge Andrade-Sierra ◽

...

Keyword(s):

Oxidative Stress ◽

Calcium Carbonate ◽

Inflammatory Cytokines ◽

C Reactive Protein ◽

Reactive Protein ◽

Sevelamer Hydrochloride ◽

Tnf Α ◽

Compensatory Effect ◽

Pro Inflammatory Cytokines

Patients with end-stage renal disease (ESRD) present alterations in mineral and bone metabolism. Hyperphosphatemia in ESRD is considered an independent risk factor for cardiovascular disease (CVD), increasing morbidity, and mortality. Sevelamer hydrochloride is a calcium-free, non-absorbable phosphate-chelating polymer. Calcium carbonate chelator is helpful in controlling serum phosphate levels. There is insufficient information on the influence of sevelamer hydrochloride and calcium carbonate on the behavior of oxidative stress (OS) markers and inflammation in patients on hemodialysis (HD). A randomized open clinical trial was carried out on patients to evaluate sevelamer hydrochloride and calcium carbonate influence at 6 months of study follow-up. Levels of oxidants (LPO, NO, and 8-isoprostanes), antioxidants (SOD and TAC), oxidative DNA damage (8-OHdG and hOGG1), pro-inflammatory cytokines (IL-6 and TNF-α), and inflammation markers (ferritin and C-reactive protein) were measured with colorimetric and ELISA methods. We found a significant increase in oxidants LPO and NO, and antioxidants SOD and TAC, and downregulation of IL-6 and TNF-α. Ferritin decrease at 6 months follow-up in the sevelamer hydrochloride group. Increase in C-reactive protein was found in the group of patients treated with calcium carbonate. In conclusion, we found an oxidative state imbalance with increase in LPO and NO oxidants. The activity of the antioxidant enzymes (SOD and TAC) was also found to increase, suggesting a compensatory effect in the face of increase in oxidants. The same phenomenon was observed with increase in the oxidative damage marker to DNA and the increase in the DNA repair enzyme, suggesting a compensatory effect. Pro-inflammatory cytokines were predominantly downregulated by TNF-α in the group that ingested sevelamer hydrochloride in the final determination at 6 months of follow-up. Serum ferritin levels decreased significantly at the end of follow-up in patients on HD in the sevelamer hydrochloride group. The management of hyperphosphatemia with sevelamer hydrochloride appears to have obvious anti-inflammatory and antioxidant benefits.

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Phosphoglycerate Mutase 1 Prevents Neuronal Death from Ischemic Damage by Reducing Neuroinflammation in the Rabbit Spinal Cord

International Journal of Molecular Sciences ◽

10.3390/ijms21197425 ◽

2020 ◽

Vol 21 (19) ◽

pp. 7425

Author(s):

Hyo Young Jung ◽

Hyun Jung Kwon ◽

Woosuk Kim ◽

Kyu Ri Hahn ◽

Seung Myung Moon ◽

...

Keyword(s):

Oxidative Stress ◽

Spinal Cord ◽

Inflammatory Cytokines ◽

Neuronal Death ◽

Microglial Activation ◽

Ventral Horn ◽

Phosphoglycerate Mutase ◽

Ischemic Damage ◽

Tnf Α ◽

Pro Inflammatory Cytokines

Phosphoglycerate mutase 1 (PGAM1) is a glycolytic enzyme that increases glycolytic flux in the brain. In the present study, we examined the effects of PGAM1 in conditions of oxidative stress and ischemic damage in motor neuron-like (NSC34) cells and the rabbit spinal cord. A Tat-PGAM1 fusion protein was prepared to allow easy crossing of the blood-brain barrier, and Control-PGAM1 was synthesized without the Tat peptide protein transduction domain. Intracellular delivery of Tat-PGAM1, not Control-PGAM1, was achieved in a time- and concentration-dependent manner. Immunofluorescent staining confirmed the intracellular expression of Tat-PGAM1 in NSC34 cells. Tat-PGAM1, but not Control-PGAM1, significantly alleviated H2O2-induced oxidative stress, neuronal death, mitogen-activated protein kinase, and apoptosis-inducing factor expression in NSC34 cells. After ischemia induction in the spinal cord, Tat-PGAM1 treatment significantly improved ischemia-induced neurological impairments and ameliorated neuronal cell death in the ventral horn of the spinal cord 72 h after ischemia. Tat-PGAM1 treatment significantly mitigated the ischemia-induced increase in malondialdehyde and 8-iso-prostaglandin F2α production in the spinal cord. In addition, Tat-PGAM1, but not Control-PGAM1, significantly decreased microglial activation and secretion of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α induced by ischemia in the ventral horn of the spinal cord. These results suggest that Tat-PGAM1 can be used as a therapeutic agent to reduce spinal cord ischemia-induced neuronal damage by lowering the oxidative stress, microglial activation, and secretion of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α.

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Benfotiamine Ameliorates High Carbohydrate Diet-Induced Hepatic Oxidative Stress, Inflammation and Apoptosis in Megalobrama Amblycephala

10.21203/rs.3.rs-77036/v1 ◽

2020 ◽

Author(s):

Chao Xu ◽

Wen-Bin Liu ◽

Hua-Juan Shi ◽

Xiang-Fei Li

Keyword(s):

Oxidative Stress ◽

Caspase 3 ◽

Megalobrama Amblycephala ◽

Mrna Levels ◽

Nuclear Factor ◽

Caspase 9 ◽

Carbohydrate Diet ◽

High Carbohydrate ◽

Tnf Α ◽

Antioxidant Enzymes Activities

Abstract Background: The impairment of immunity induced by high-carbohydrate diet is closely associated with the development of glucose metabolic disorders. In the study of diabetes, benfotiamine can prevent β-cell dysfunction by inhibiting inflammation, thereby improving insulin resistance. However, information regarding the effects of this substance on aquatic animals is extremely scarce.Methods: A 12-week nutritional research was conducted to evaluate the influences of benfotiamine on the growth performance, oxidative stress, inflammation and apoptosis in Megalobrama amblycephala (45.25 ± 0.34 g) fed high-carbohydrate (HC) diets. Six experimental diets were formulated, containing a control diet (30% carbohydrate, C), a HC diet (43% carbohydrate), and the HC diet supplemented with four graded benfotiamine levels (0.7125 (HCB1), 1.425 (HCB2), 2.85 (HCB3), and 5.7 (HCB4) mg/kg).Results: HC diet intake remarkably decreased daily growth coefficient (DGC), growth rate per metabolic body weight (GRMBW), feed intake (FI), liver antioxidant enzymes activities, sirtuin-1 (SIRT1) protein expression as well as liver mRNA levels of SIRT1, nuclear factor erythroid 2-related factor 2 (Nrf2), catalase (CAT), manganese superoxide dismutase (Mn-SOD), interleukin10 (IL10) than those of the control group, but the opposite was true for plasma activities of alanine transaminase (AST) and aspartate aminotransferase (ALT), and contents of interleukin 1β (IL1β) and interleukin 6 (IL6), liver contents of malondialdehyde (MDA), and mRNA levels of kelch-like ECH associating protein 1 (Keap1), nuclear factor kappa B (NF-κB), tumour necrosis factor α (TNF α), IL1β, IL6, Bax, Caspase 3, Caspase 9 and P53. As with benfotiamine supplementation, HCB2 diet remarkably increased DGC, GRMBW, liver antioxidant enzymes activities, SIRT1 protein expression as well as liver mRNA levels of SIRT1, Nrf2, CAT, Mn-SOD, IL10 and Bcl2, while the opposite was true for plasma activities of AST and ALT, and contents of IL1β and IL6, liver MDA contents as well as mRNA levels of Keap1, NF-κB, TNF α, IL1β, IL6, Bax, Caspase 3, Caspase 9 and P53.Conclusion: Benfotiamine at 1.425 mg/kg can improve the growth performance and alleviate the oxidative stress, inflammation and apoptosis of M. amblycephala fed HC diets through the activation of the SIRT1 pathway.

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Alleviation of doxorubicin–induced hepatorenal toxicities with sesamin via the suppression of oxidative stress

Human & Experimental Toxicology ◽

10.1177/0960327115626581 ◽

2016 ◽

Vol 35 (11) ◽

pp. 1183-1193 ◽

Cited By ~ 6

Author(s):

H Guo ◽

Y Liu ◽

L Wang ◽

G Zhang ◽

S Su ◽

...

Keyword(s):

Oxidative Stress ◽

Antioxidant Activity ◽

Alkaline Phosphatase ◽

Serum Creatinine ◽

Kidney Injury ◽

Treated Group ◽

Anthracycline Antibiotics ◽

Histological Damage ◽

Liver And Kidney ◽

Mda Content

Hepatorenal toxicities are an important side effect of anthracycline antibiotics. The objective of this study was to determine whether sesamin (Ses) protects against acute doxorubicin (DOX)-induced hepatorenal toxicities. Rats received daily treatment with either 0.5% carboxymethylcellulose (10 mL/kg) or Ses (10, 20 and 40 mg/kg) orally for 10 days, followed by an intravenous injection at day 8 of either saline (10 mL/kg) or DOX (20 mg/kg). Hepatorenal toxicity was assessed by measuring the levels of serum creatinine (Cre), blood urea nitrogen (BUN), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP). The protein expression of 4-hydroxynonenal (4-HNE) in hepatorenal tissues was evaluated using immunohistochemistry. The malondialdehyde (MDA) content and antioxidant activity in the kidney and liver tissues were also measured. The results suggest that pretreatment with Ses ameliorated DOX-induced liver and kidney injury by lowering the serum ALT, AST, ALP, Cre and BUN levels ( p < 0.05 or p < 0.01), and the histological damage to the liver and kidney tissues induced by DOX compared to control were also significantly attenuated by Ses. Furthermore, Ses significantly decreased the DOX-induced increase of MDA and 4-HNE and increased the activity of CAT, SOD and GPX compared to the DOX-treated rats ( p < 0.05 or p < 0.01), whereas the change of DOX + Ses (10 mg/kg) group is not significant compared to the DOX-treated group ( p > 0.05). These findings indicate that Ses elicits a typical protective effect against DOX-induced acute hepatorenal toxicity via the suppression of oxidative stress.

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