scholarly journals Protective Effects of Taurine Against Inflammation and Apoptosis in Cadmium-Induced Hepatotoxicity

Author(s):  
Jiaming Zheng ◽  
Guobin Qiu ◽  
Yewen Zhou ◽  
Kezhe Ma ◽  
Sheng Cui

Abstract Cadmium (Cd), a heavy metal contaminant,which seriously threatens human and animal health. Taurine (Tau) has been used to against hepatotoxicity caused by different environmental toxins. However, it has not been elucidated whether Tau exerts its protective function against Cd-induced hepatotoxicity. The aim of this study was thus to evaluate the ameliorative function of Tau on Cd-induced liver toxicity in mice. The histopathologic and ultrastructure changes, as well as alterations in indexes related to liver function, antioxidant biomarkers, inflammatory and apoptosis were evaluated. The results showed that Tau alleviated the vacuolar degeneration, nuclear condensation, mitochondria swelling and cristae lysis of hepatocytes induced by Cd. In addition, Tau treatment significantly restored the ALT, AST levels in serum, and inflammatory factor TNF-α and IL-1β in liver tissue. Furthermore, Tau treatment decreased the Bax/Bcl-2 ratio and cleaved caspase-3 protein expression levels. Taken together, these observations demonstrate that Tau has important hepatic protective function against the inflammation and apoptosis induced by Cd.

Author(s):  
Hala Salah Abdel Kawy Eweis ◽  
Omnyah Mohammad Omar Bashraf ◽  
Ahmed Shaker Ali ◽  
Soad Shaker Ali

Background and Aim: Cisplatin "cis diamminedichloroplatinum [II] (CDDP) is the most widely used drug in cancer chemotherapy and hepatotoxicity is one of its major side effects. Vorinostat (VST) has been recognized to have an antioxidant and anti-inflammatory effect in low doses. The present study aimed to explore the potential protective effects of low dose VST against CDDP induced-liver toxicity in male Wistar rats. Methods: The rats were randomly divided into 4 groups (10 rats each); I-control group, II-CDDP group (7.5 mg/kg I.P. single dose 5 days before the end of the experiment) III-, VST group (15 mg/kg/day by gastric gavage for 28 days) and IV-CDDP + VST group (as in group II & III). Blood and livers samples were collected at the day 28th for biochemical and histopathological examinations. Results: Administration of CDDP significantly decrease hepatic GSH levels and increase serum alanine transaminase, aspartate transaminase and hepatic MDA, p53, TNF-α, and NF-κB levels compared to control. Pretreatment with VST significantly attenuated all unfavorable changes in these parameters. Histopathological analysis showed that VST significantly decreased liver inflammatory and degenerative changes induced by CDDP. VST also significantly increased Bcl-2 and decreased Caspas-3 immunoexpression in hepatic tissues. Conclusion: VST alleviates CDDP induced hepatic toxicity in rats by modulating MDA, p53, TNF-α, and NF-κB. It also significantly increased Bcl-2 and decreased Caspase-3.


2019 ◽  
Vol 14 (7) ◽  
pp. 1934578X1986417
Author(s):  
Beibei Zhang ◽  
Mengnan Zeng ◽  
Meng Li ◽  
Wenjing Chen ◽  
Benke Li ◽  
...  

This study investigated the protective effects of guaiane-type sesquiterpenoids isolated from Dendranthema morifolium (Ramat.) S. Kitam flowers on lipopolysaccharide (LPS)-induced injury in H9c2 cardiomyocyte. Cell viability was determined by thiazolyl blue tetrazolium bromide (MTT). The content of released tumor necrosis factor alpha (TNF- α) and interleukin 6 (IL-6) was evaluated by enzyme-linked immunosorbent assay. The levels of lactate dehydrogenase (LDH) and creatine phosphate kinase (CK) were measured by using commercial available kits. The protein expression levels of pelF2 α, GRP78, Bax, caspase-3, caspase-9, Bcl-2, LC3-II, and p62 were measured by in-cell Western. Flow cytometry was used to detect H9c2 cardiomyocyte apoptosis. Compounds 5, 7, 1, 8, and 2 exhibited the effects of cardioprotection and activity sequence enhancement. The levels of IL-6, TNF- α, LDH, CK, pelF2 α, GRP78, Bax, caspase-3, caspase-9, p62, and H9c2 cardiomyocyte apoptosis were increased in LPS-treated H9c2 cardiomyocyte, while those of Bcl-2 and LC3-II were decreased. These effects could be effectively reversed by compounds 5, 7, 1, 8, and 2. Results demonstrated that the guaiane-type sesquiterpenoids could prevent LPS-induced injury in cardiomyocyte by decreasing endoplasmic reticulum (ER) stress, apoptosis, and autophagy as well as downregulating the inflammatory mediators. In addition, the active groups of guaiane-type sesquiterpenoids might be the angelate at C-8 and the exocyclic double bond at C-11.


2020 ◽  
Author(s):  
Jin Xu ◽  
Xiaozhong Qian ◽  
Ren Ding

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.


Author(s):  
HEBA A. M. MOUSA

Objective: This study aimed to investigate the possible protective effect of rutin in management of TiO2NPs-induced renal injury in mice. Methods: Forty male Swiss albino mice were randomly divided into four groups (n=10). Group (I) served as a control group, group (II) received 100 mg/kg body weight (b. wt) of rutin (orally), group (III) received 70 mg/kg b. wt of TiO2NPs,injected intraperitoneally (i. p.), Group (IV) received 70 mg/kg b. wt of TiO2NPs plus 100 mg/kg b. wt of rutin; for 14 successive days. The renal toxicity was determined through evaluating the renal function biomarkers (serum creatinine, urea, and uric acid) and the levels of malondialdehyde (MDA), reduced glutathion (GSH), nuclear factor kappa B (NF-kB), tumor necrosis factor-α (TNF)-α, B-cell lymphoma (BCL)-2 and caspase-3 in renal tissues. Results: Administration of TiO2NPs plus rutin prevented the deleterious effect of TiO2NPs on mice kidneys through improving the renal functions, and alleviating the increase in MDA, NF-kB, TNF-α, and caspase-3 levels, as well as the decrease in GSH andBCL-2 levels, in renal tissues. Conclusion: Taken together, these findings suggested that rutin plays a role in alleviating TiO2NPs-induced oxidative stress, inflammation, and apoptosis, and exerts renal protective effects.


2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Yin Guan ◽  
Xiaoqian Zhao ◽  
Weiwei Liu ◽  
Yue Wang

Abstract Objective Galuteolin (Galu) is a substance extracted and purified from honeysuckle. The purpose of this study was to explore the effects of Galu on the TNF-α-induced RA-FLS cells (synoviocytes) and reveal its potential molecular mechanism from the perspectives of anti-apoptosis and anti-inflammation. Methods After TNF-α stimulation, cell proliferation of RA-FLS was assessed by CCK-8 assay. TUNEL staining was used to detect the apoptosis. Western blot was used to detect the expressions of Iκκβ, p-p65, p65, p-IκB, IκB, Cleaved-caspase3, Caspase-3, Bcl-2, and Bax. HO-1 were determined by RT-PCR. The contents of pro-inflammatory cytokines IL-1β, IL-6, IL-8, and MMP-1 were determined by ELISA. Results Galu significantly suppressed cell proliferation in a dose-dependent manner. Additionally, Galu obviously promotes cell apoptosis rate of RA-FLS cells and elevated the expression levels of HO-1, caspase-3, and Bax, while reducing the expression level of Bcl-2. Furthermore, Galu apparently inhibited the levels of Iκκβ, p-p65, and p-IκB. Moreover, Galu also significantly reduced the levels of pro-inflammatory factors IL-1β, IL-6, IL-8, and MMP-1 in RA-FLS cells. Conclusion Galuteolin exerts protective effects against TNF-α-induced RA-FLS cells by inhibiting apoptosis and inflammation, which can guide the clinical use of rheumatoid arthritis.


2020 ◽  
Vol 98 (3) ◽  
pp. 147-155 ◽  
Author(s):  
Saber Ghazizadeh Darband ◽  
Ehsan Saboory ◽  
Shirin Sadighparvar ◽  
Mojtaba Kaviani ◽  
Kazhal Mobaraki ◽  
...  

This study aimed to investigate the underlying mechanisms in anti-tumorigenesis effects of exercise through evaluation of inflammation and apoptosis. Twenty-four Wistar rats were divided into control, exercise, 1,2-dimethylhydrazine (DMH), and DMH + exercise. After a week, rats in the DMH group were given DMH twice a week for 2 weeks. Animals in the exercise groups performed exercise on a treadmill 5 days/week for 8 weeks. After 8 weeks of training, levels of COX-2, PCNA, Bax, Bcl-2, and procaspase-3/cleaved caspase-3 were assessed. Histological changes, number of aberrant crypt foci (ACF), and serum levels of TNF-α and IL-6 were also analyzed. ACF number was significantly decreased following the exercise program. Protein levels of COX-2 and PCNA and serum levels of IL-6 and TNF-α were significantly elevated in the rats receiving DMH and downregulated after performing the exercise program (P < 0.05). Exercise upregulated apoptosis, which was evident from the increased Bax/Bcl2 ratio, and enhanced the expression levels of activated caspase-3 as compared to the DMH group. The colonic architecture was improved in DMH + exercise. Exercise can effectively attenuate DMH-induced increase of inflammatory markers. Exercise induces apoptosis at the downstream of the inflammatory response. Therefore, exercise may play a role as a moderator of inflammation to exert protective effects against colon cancer.


2021 ◽  
Author(s):  
Sefa Küçükler ◽  
Fatih Mehmet Kandemir ◽  
Selçuk Özdemir ◽  
Selim Çomaklı ◽  
Cuneyt Caglayan

Abstract Deltamethrin (DLM) is a type-II pyrethroid synthetic insecticide that is extensively used for controlling mosquitoes, flies, pests, insects worldwide. Oxidative stress is one of the DLM toxicity mechanisms. This study was carried out to evaluate the likelihood protective effects of rutin (RUT), a natural antioxidant, against DLM-induced liver and kidney toxicities in rats. Hepatotoxicity and nephrotoxicity were evaluated after the rats were treated orally with DLM (1.28 mg/kg b.w.) alone or with RUT (25 and 50 mg/kg b.w.) for 30 days. DLM administration caused an increase in lipid peroxidation level and a decrease in activities of SOD, CAT, and GPx and GSH levels in the both tissues. DLM also increased serum ALT, AST, ALP, urea, and creatinine levels, while reduced nephrine levels in rats. In addition, DLM increased the activation of inflammatory and apoptotic pathways by decreasing Bcl-2 and increasing TNF-α, NF-κB, IL-1β, p38α MAPK, COX-2, iNOS, beclin-1, Bax, and caspase-3 protein levels and/or activities. Furthermore, DLM increased mRNA expression levels of PARP-1, VEGF and immunohistochemical expressions of c-fos in the tissues. RUT treatment significantly improved all examined parameters and restored the liver and kidney histopathological and immunohistochemical alterations. These findings demonstrate that RUT could be used to ameliorate hepatotoxicity and nephrotoxicity associated with oxidative stress, inflammation, and apoptosis in DLM-induced rats.


2019 ◽  
Vol 69 (2) ◽  
pp. 177-191 ◽  
Author(s):  
Hidayet Tutun ◽  
Özlem Özmen ◽  
İbrahim Aktaş ◽  
Alper Yalçin ◽  
Ahmet Türk

Abstract Artemisinin, an antimalarial drug, has anticancer activity and possesses protective effects against several tissue injuries. The aim of the present study was to investigate the effects of artemisinin on doxorubicin-induced renal and testicular toxicity in rats. Doxorubicin was administered to rats at a single dose of 10 mg/kg body weight (b.w.) as a single intraperitoneal injection. Application of artemisinin was by using oral gavage feeding needle for 14 days at different specified doses (7 mg/kg and 35 mg/kg b.w.). At the end of the experiments, kidney and testis samples were collected and used for histopathological and immunohistochemical examinations. At histopathological examination, while hyperemia was the marked finding in kidney and testis of rats treated with doxorubicin only, no evidence of structural abnormalities showed in other groups. Immunohistochemical examination of the testes and kidneys demonstrated significantly increased expression of caspase-3, TNF-α, iNOS and NF-κB in rats treated with doxorubicin only. Artemisinin decreased the doxorubicin-induced overexpression of NF-κB, iNOS, TNFα and caspase-3 in these tissues of rats. Artemisinin can protect the kidney and testis against doxorubicin-induced nephrotoxicity and testotoxicity, probably through a decrease of caspase-3, TNF-α, iNOS and NF-κB expressions. It may be concluded that artemisinin has a potential for clinical use in the treatment of kidney and testis damage induced by doxorubicin. Further researches are required to determine the appropriate combination of artemisinin with doxorubicin.


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