Protective effects of thymoquinone and methotrexate on the renal injury in collagen-induced arthritis

We previously showed that inhibition of soluble epoxide hydrolase (sEH) increased epoxyeicosatrienoic acids (EETs) levels and reduced renal injury in diabetic mice and these changes were associated with induction of hemeoxygenase-1 (HO-1). The present study determines whether the inhibition of HO negates the reno-protective effect of sEH inhibition in diabetic spontaneously hypertensive rats as a model of diabetic nephropathy in which hypertension coexists with diabetes. After six weeks of induction of diabetes with streptozotocin, SHR were divided into the following groups: untreated, treated with the sEH inhibitor, trans -4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (AUCB), treated with the HO inhibitor, stannous mesoporphyrin (SnMP), and treated with both inhibitors for four more weeks; non diabetic SHR served as a control group. Although inhibition of sEH increased renal EETs/DHETEs ratio and HO-1 activity in diabetic SHR, it did not significantly alter blood pressure (plasma EETs/DHETEs ratio was 0.5± 0.1 in AUCB-treated vs. 0.1± 0.01 in untreated diabetic SHR, P<0.05). Treatment of diabetic SHR with AUCB reduced the elevation in urinary albumin and nephrin excretion (albuminuria was 6.5± 0.5 in AUCB-treated diabetic SHR vs. 9± 1.7 mg/day in untreated diabetic SHR and nephrinuria was 70±11 in AUCB-treated diabetic SHR vs. 111± 9 μg/day in untreated diabetic SHR, P<0.05) whereas co-administration of SnMP with AUCB prevented these changes (albuminuria was 10.6± 0.6 mg/day and nephrinuria was 91±11 μg/day). Immunohistochemical analysis revealed elevations in renal fibrosis and apoptosis as evidenced by increased renal TGF-β, fibronectin and annexin V expression in diabetic SHR and these changes were reduced with sEH inhibition. Co-administration of SnMP with AUCB prevented its ability to reduce renal fibrosis and apoptosis in diabetic SHR. In addition, SnMP treatment also prevented AUCB-induced decreases in renal macrophage infiltration and renal TGF-β, NFκB and MCP-1 levels in diabetic SHR. These data suggest that HO-1 induction is involved in the protective effect of sEH inhibition against diabetic renal injury.

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Protective effects of Eucommia lignans against hypertensive renal injury by inhibiting expression of aldose reductase

Journal of Ethnopharmacology ◽

10.1016/j.jep.2011.11.032 ◽

2012 ◽

Vol 139 (2) ◽

pp. 454-461 ◽

Cited By ~ 16

Author(s):

Ling Li ◽

Jin Yan ◽

Kai Hu ◽

Juan Gu ◽

Jun-Jie Wang ◽

...

Keyword(s):

Aldose Reductase ◽

Renal Injury ◽

Protective Effects

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Gut microbiota mediated the protective effects of tuna oil on collagen-induced arthritis in mice

Food & Function ◽

10.1039/d1fo00709b ◽

2021 ◽

Author(s):

Chenyang Lu ◽

Ju Chen ◽

Congmin Yi ◽

Jiaojiao Han ◽

Qiuyue Shi ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Autoimmune Disease ◽

Gut Microbiota ◽

Protective Effects ◽

Collagen Induced Arthritis ◽

Tuna Oil ◽

Beneficial Effects ◽

Chronic Autoimmune Disease

Rheumatoid arthritis is emerging as a chronic autoimmune disease worldwide. In this study, the components of tuna oil (TO) were firstly measured, and the beneficial effects of TO on collagen-induced...

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Hydrogen Gas Alleviates Chronic Intermittent Hypoxia-Induced Renal Injury through Reducing Iron Overload

Molecules ◽

10.3390/molecules24061184 ◽

2019 ◽

Vol 24 (6) ◽

pp. 1184 ◽

Cited By ~ 3

Author(s):

Peng Guan ◽

Zhi-Min Sun ◽

Li-Fei Luo ◽

Ya-Shuo Zhao ◽

Sheng-Chang Yang ◽

...

Keyword(s):

Oxidative Stress ◽

Iron Overload ◽

Renal Injury ◽

Intermittent Hypoxia ◽

Hydrogen Gas ◽

Chronic Intermittent Hypoxia ◽

Protective Effects ◽

Divalent Metal Transporter 1 ◽

Divalent Metal Transporter ◽

And Oxidative Stress

Iron-induced oxidative stress has been found to be a central player in the pathogenesis of kidney injury. Recent studies have indicated H2 can be used as a novel antioxidant to protect cells. The present study was designed to investigate the protective effects of H2 against chronic intermittent hypoxia (CIH)-induced renal injury and its correlation mechanism involved in iron metabolism. We found that CIH-induced renal iron overloaded along with increased apoptosis and oxidative stress. Iron accumulates mainly occurred in the proximal tubule epithelial cells of rats as showed by Perl’s stain. Moreover, we found that CIH could promote renal transferrin receptor and divalent metal transporter-1 expression, inhibit ceruloplasmin expression. Renal injury, apoptosis and oxidative stress induced by CIH were strikingly attenuated in H2 treated rats. In conclusion, hydrogen may attenuate CIH-induced renal injury at least partially via inhibiting renal iron overload.

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P0522INHIBITING 15-PGDH PREVENTS ISCHEMIC RENAL INJURY BY A PGE2/EP4 SIGNALING PATHWAY MEDIATING VASODILATION, INCREASED RENAL BLOOD FLOW, AND INCREASED ADENOSINE/A2A RECEPTOR

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0522 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Byeong Woo KIm ◽

Sun hee Kim ◽

Ki beom Bae

Keyword(s):

Blood Flow ◽

Renal Blood Flow ◽

Renal Injury ◽

Ischemia Reperfusion ◽

Adenosine A2a Receptor ◽

Vehicle Group ◽

Control Group ◽

Protective Effects ◽

A2a Receptor ◽

Adenosine A2a

Abstract Background and Aims We demonstrate the marked activity of SW033291, an inhibitor of 15-hydoxyprostaglandin dehydrogenase (15-PGDH), in preventing acute kidney injury (AKI) in a murine model of ischemia reperfusion injury (IRI). AKI due to ischemic injury represents a significant clinical problem. Prostaglandin E2 (PGE2) is vasodilator in the kidney, but is rapidly degraded in vivo due to catabolism by 15-PGDH. We investigated the potential of SW033291, a potent and specific 15-PGDH inhibitor, as prophylactic treatment for ischemic AKI. Method 10-week aged male C57/BL6 mice were randomly allocated to five groups (n=8 to 15 in each group): the sham-control group, sham-SW033291 group, IRI-vehicle group, IRI-indomethacin group and the IRI-SW033291 group. IRI were induced by clamping bilateral renal artery for 30 min followed by 24 hours of reperfusion. Vehicle, indomethacin, or SW033291 were intraperitoneally administered three times at 1 hour before, immediately after, and 12 hours after IRI. Renal function, histological changes, and renal blood flow were compared and the relevant parameters of oxidative stress and inflammation were detected. Results Prophylactic administration of SW033291 significantly increased renal tissue PGE2 levels and increased post-AKI renal blood flow and renal arteriole area. In parallel, prophylactic SW033291 decreased post-AKI histologic injury score and tubular apoptosis and markedly reduced biomarkers of renal injury that included BUN, creatinine, NGAL and KIM-1. Prophylactic SW033291 also reduced post-AKI induction of proinflammatory cytokines, high mobility group box 1 (HMGB1), and malondialdehyde (MDA). Protective effects of SW033291 were mediated by PGE2 signaling as they could be blocked by pharmacologic inhibition of PGE2 synthesis or of the EP4 type PGE2 receptor. Consistent with activation of PGE2 signaling, SW033291 induced renal levels of both EP4 and of cyclic adenosine monophosphate (cAMP), along with other vasodilatory effectors including AMP, adenosine, and the adenosine A2A receptor (A2A). Protective effects of SW0333291 could largely be achieved with a single prophylactic dose of the drug. Conclusion Inhibiting 15-PGDH may thus represent a novel strategy for prophylaxis of ischemic AKI in multiple clinical settings, including renal transplantation and cardiovascular surgery.

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Sodium Glucose Co-Transporter 2 Inhibitor Ameliorates Autophagic Flux Impairment on Renal Proximal Tubular Cells in Obesity Mice

International Journal of Molecular Sciences ◽

10.3390/ijms21114054 ◽

2020 ◽

Vol 21 (11) ◽

pp. 4054

Author(s):

Kazuhiko Fukushima ◽

Shinji Kitamura ◽

Kenji Tsuji ◽

Yizhen Sang ◽

Jun Wada

Keyword(s):

Renal Injury ◽

Tubular Damage ◽

Autophagic Flux ◽

Protective Effects ◽

Renal Protection ◽

Proximal Tubular Cells ◽

Tubular Cells ◽

Proximal Tubular ◽

Renal Proximal Tubular Cells ◽

Renal Proximal Tubular

Obesity is supposed to cause renal injury via autophagy deficiency. Recently, sodium glucose co-transporter 2 inhibitors (SGLT2i) were reported to protect renal injury. However, the mechanisms of SGLT2i for renal protection are unclear. Here, we investigated the effect of SGLT2i for autophagy in renal proximal tubular cells (PTCs) on obesity mice. We fed C57BL/6J mice with a normal diet (ND) or high-fat and -sugar diet (HFSD) for nine weeks, then administered SGLT2i, empagliflozin, or control compound for one week. Each group contained N = 5. The urinary N-acetyl-beta-d-glucosaminidase level in the HFSD group significantly increased compared to ND group. The tubular damage was suppressed in the SGLT2i–HFSD group. In electron microscopic analysis, multi lamellar bodies that increased in autophagy deficiency were increased in PTCs in the HFSD group but significantly suppressed in the SGLT2i group. The autophagosomes of damaged mitochondria in PTCs in the HFSD group frequently appeared in the SGLT2i group. p62 accumulations in PTCs were significantly increased in HFSD group but significantly suppressed by SGLT2i. In addition, the mammalian target of rapamycin was activated in the HFSD group but significantly suppressed in SGLT2i group. These data suggest that SGLT2i has renal protective effects against obesity via improving autophagy flux impairment in PTCs on a HFSD.

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Protective Effects and Mechanisms of Rosuvastatin on Acute Kidney Injury Induced by Contrast Media in Rats

International Journal of Nephrology ◽

10.1155/2020/3490641 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Zehui Jiang ◽

Jun Zhang ◽

Yuanan Lu

Keyword(s):

Protective Effect ◽

Contrast Medium ◽

Renal Injury ◽

Intervention Group ◽

Inflammatory Factors ◽

Control Group ◽

Renal Tubules ◽

Protective Effects ◽

Sod Activity ◽

Biochemical Indicators

Objective. To explore the protective effect and mechanism of rosuvastatin on acute renal injury induced by a nonionic hypotonic contrast medium in rats. Methods. Forty-eight healthy adult SD rats were randomly divided into three groups: normal control group (NC); contrast medium control group (CM); and rosuvastatin intervention group (RI). The RI group was intragastrically administered with a 10 mg/kg of rosuvastatin 12 h prior to the contrast exposure. All rats in CM and RI groups were inoculated with 10 mL/kg of chemical (IV) while the same volume of saline for the NC group. At 24 h and 72 h posttreatments, pathomorphological changes of renal tubules were documented, respectively, and several biochemical indicators were tested to assess renal injury of experimental rats. Results. Compared with the CM group, rats in the RI group showed significantly reduced injury of kidneys and decreased levels of biochemical indicators such as blood Scr, blood Cys-C, urine NAG, urine α1-MG, and urine mALB. The serum Hs-CRP in the CM group increased significantly from 24 h to 72 h (p<0.05), but this was not observed in the rats of the RI group. In addition, SOD activity in the RI group was significantly increased (p<0.01) while SOD activity in renal tissue decreased significantly with time in the CM group (p<0.05). Conclusion. Short-term intervention with rosuvastatin can lead to reduced kidney damage associated with the contrast agent by reducing the levels of inflammatory factors and oxidative stress. Thus, rosuvastatin intervention has a protective effect on rats from contrast-induced nephropathy.

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P1572EFFECTIVENESS OF COENZYME Q10-MICELLE COMPARED WITH COENZYME Q10 ON TACROLIMUS-INDUCED RENAL INJURY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1572 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Sheng Cui ◽

Kang Luo ◽

Yi Quan ◽

Sun Woo Lim ◽

Chul-Woo Yang

Keyword(s):

Oxidative Stress ◽

Coenzyme Q10 ◽

Renal Injury ◽

Apoptotic Cell ◽

Oxidative Stress Marker ◽

Protective Effects ◽

Sprague Dawley ◽

Male Adult ◽

Sprague Dawley Rats ◽

Pathologic Lesions

Abstract Background and Aims We and others have recently demonstrated that Coenzyme Q10 (CoQ10) has protective effects against diabetes mellitus and various types of renal injury. This study investigated whether CoQ10-micelle treatment would affords superior renoprotection compared with CoQ10 in the governing tacrolimus (Tacrolimus)-induced renal injury in the rats. Method Male adult Sprague-dawley Rats were treated daily with Tacrolimus (1.5mg/kg/day, subcutaneous), CoQ10 (20mg/kg/day, oral), and CoQ10-micelle (20 mg/kg/day, oral) for 4 weeks. The effects of CoQ10 orCoQ10-micelle on Tac-induced renal injury were assessed in terms of renal function, histopathology, oxidative stress and apoptotic cell death. Results After 4 weeks of Tacrolimus treatment to rats caused renal dysfunction, typical pathologic lesions, and oxidative stress marker. The serum creatinine was reduced by Tac co-treatment with CoQ10 or CoQ10-micelle groups compared with the Tac and VH group (0.31 ± 0.03 in the VH group vs. 0.43 ± 0.041 in the Tac group vs.0.37 ± 0.031 in the Tac+CoQ10 group 0.30 ± 0.02123 in the Tac+CoQ10-micellegroup; 1P<0.05 vs. VH. 2P<0.05 vs. TAC. . 3P<0.05 vs. TAC+C.) The administration of CoQ10-micelle improved renal immunoreactivity, which was accompanied by reductions in oxidative stress and apoptosis. Assessment of the mitochondrial ultrastructure by electron microscopy revealed that tacrolimus co-treatment with CoQ10-micelle increased the size and number of mitochondria more than co-treatment with CoQ10, compared with that induced by TAC treatment alone. Conclusion These findings suggest that both CoQ10 and CoQ10-micelle effectively attenuates Tac-induced renal injury, and CoQ10-micelle provides more benefits than that of CoQ10.

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