scholarly journals Protective Role of Loranthus regularis against Liver Dysfunction, Inflammation, and Oxidative Stress in Streptozotocin Diabetic Rat Model

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Ahmed Z. Alanazi ◽  
Faleh Alqahtani ◽  
Ramzi A. A. Mothana ◽  
Mohamed Mohany ◽  
Hatem M. Abuohashish ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Enzymatic Activities ◽  
Cellular Damage ◽  
Hepatic Tissue ◽  
Albino Rats ◽  
Prostaglandin E ◽  
Therapeutic Effects ◽  
Tnf Α

Earlier studies revealed the potential therapeutic values of Loranthus regularis (L. regularis). This study evaluated Loranthus regularis (L. regularis) extract systemic antidiabetic effects and benefits against diabetic hepatocellular injuries through antioxidant and anti-inflammatory pathways using the streptozotocin (STZ) model in Wistar albino rats. After diabetes induction, animals were orally treated with L. regularis extract for 4 weeks. Serum levels of glucose, insulin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), total triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were estimated. Furthermore, tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), caspase-3, nitric oxide (NO), and prostaglandin E-2 (PGE-2) were estimated in serum. In liver, thiobarbituric acid reactive substances (TBARSs) and reduced glutathione (GSH) as well as the proinflammatory cytokines and enzymatic activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reeducates (GR), and glutathione-S-transferase (GST) were assayed. Finally, the degree of hepatic tissue damage was evaluated histologically. Treatment of the diabetic rats with L. regularis extract markedly reduced the elevated serum levels of glucose, ALT, AST, TC, TG, LDL, TNF-α, IL-1β, IL-6, caspase-3, NO, and PGE-2. L. regularis extract also improved serum levels of insulin and HDL. The elevated TBARS, TNF-α, IL-1β, and IL-6 levels in hepatic tissue of diabetic animals were reduced by L. regularis. Moreover, L. regularis extract significantly restored the diminished hepatic GSH level and enzymatic activities of SOD, CAT, GPx, GR, and GST in diabetic animals. The biochemical protective effects of L. regularis were associated with improved histological hepatocellular integrity and architecture. Taken together, L. regularis has therapeutic effects against diabetic-induced hepatic complications. The restored liver functions and cellular damage might be mediated through free radicals scavenging and proinflammatory cytokine inhibition.

l-Carnitine-induced amelioration of HFD-induced hepatic dysfunction is accompanied by a reduction in hepatic TNF-α and TGF-β1

2018 ◽  
Vol 96 (6) ◽  
pp. 713-725 ◽  
Author(s):  
Mabrouk Attia Abd Eldaim ◽  
Fatma Mohamed Ibrahim ◽  
Saher Hassan Orabi ◽  
Azza Hassan ◽  
Hesham Saad El Sabagh
Keyword(s):  
Protein Expression ◽  
High Density Lipoprotein ◽  
Body Mass ◽  
Density Lipoprotein ◽  
Basal Diet ◽  
Serum Levels ◽  
High Density ◽  
Control Group ◽  
Tnf Α ◽  
Tgf Β1

In this study, we evaluated the possible mechanisms through which l-carnitine ameliorates the adverse effects from obesity in rats, induced with a high-fat diet (HFD). For this, 56 albino Wister rats were randomly assigned to 7 groups. The control group was fed a basal diet and injected with saline. The second group was fed the basal diet and injected with l-carnitine (200 mg/kg body mass, by intraperitoneal injection; i.p.). The third group were fed the HFD. The fourth group was fed the HFD and injected with l-carnitine (200 mg/kg body mass, i.p.) for 8 weeks. The fifth group was fed the HFD for 10 weeks. The sixth group were fed the HFD for 10 weeks and were also injected with l-carnitine (200 mg/kg body mass, i.p.) during the final 2 weeks. The seventh group was fed the HFD diet for 8 weeks then the basal diet for 2 weeks. The HFD induced significantly increased levels of hyperglycemia, lipid peroxidation, pathological changes, TNF-α and TGF-β1 protein expression in hepatic tissue, food intake, body weight gain, serum levels of total and non-high-density lipoprotein cholesterol, ketone bodies, triacylglycerol, urea, creatinine, AST, and ALT. However, the HFD diet significantly decreased serum levels of high-density lipoprotein (HDL) and hepatic levels of reduced glutathione. l-Carnitine ameliorated the effects of the HFD on the above-mentioned parameters. This study indicated that l-carnitine had protective and curative effects against HFD-induced hepatosteatosis by reducing hepatic oxidative stress and protein expression of TNF-α and TGF-β1.

scholarly journals Fructo-oligosaccharides lower serum lipid levels and suppress high-fat/high-sugar diet-induced inflammation by elevating serum and gut levels of short-chain fatty acids

2019 ◽  
Vol 48 (4) ◽  
pp. 030006051989671
Author(s):  
Renqiang Yu ◽  
Yongxiang Yin ◽  
Minkai Cao ◽  
Danni Ye ◽  
Yinghui Zhang ◽  
...  
Keyword(s):  
Serum Lipid ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Lipid Levels ◽  
High Fat ◽  
Serum Lipid Levels ◽  
Tnf Α

Objective This study aimed to investigate the effects of fructo-oligosaccharides (FOS) on serum lipid levels and to determine the mechanisms underlying these effects and the potential role of inflammation. Methods Male C57BL/6 mice received a normal diet, a high-fat/high-sugar (HFS) diet, or an HFS diet supplemented with 10% FOS for 10 weeks. In vivo intestinal and serum short-chain fatty acid (SCFA) levels were measured by gas chromatography. In vivo serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and malonaldehyde (MDA) were also measured. Lipid accumulation was visualized. Reactive oxygen species (ROS) generation was evaluated and apoptosis was quantified. Results FOS reversed in vivo HFS-induced lipid accumulation in the liver. An HFS diet increased ALT, AST, TC, TG, and LDL serum levels, decreased HDL serum levels, and increased IL-6, TNF-α, 8-OHdG, and MDA levels. These changes were reduced by FOS. FOS also increased intestinal and serum levels of short chain fatty acids (SCFAs). In vitro, SCFAs ameliorated palmitic acid-induced ROS production and apoptosis of HepG2 cells. Conclusion FOS supplementation lowers serum lipid levels and ameliorates HFS-induced inflammation by upregulating SCFAs.

scholarly journals Hepatoprotective effect of aqueous extract of cardamom against gentamicin induced hepatic damage in rats

2015 ◽  
Vol 5 (1) ◽  
pp. 1 ◽  
Author(s):  
Mohamed Aboubakr ◽  
Abdelazem Mohamed Abdelazem
Keyword(s):  
Aqueous Extract ◽  
Histopathological Examination ◽  
Low Density Lipoprotein ◽  
Elevated Serum ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Hepatoprotective Activity ◽  
Lipoprotein Cholesterol ◽  
Albino Rats ◽  
Aqueous Extracts

<p>The study was designed to evaluate the hepatoprotective activity of aqueous extract of cardamom in acute experimental liver injury induced by gentamicin. Twenty four male albino rats were randomly divided into four groups (six rats in each). Animals of the first group served as control and orally (p.o.) received (1 ml/kg saline). The second experimental group was given gentamicin (80 mg/kg i.p.) for 7 days. Third and fourth groups were given aqueous extract of cardamom (100 and 200 mg/kg p.o.) + gentamicin for 7 days, respectively. The degree of hepatoprotection was measured using serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, albumin, and lipid profile levels. In the acute liver damage induced by gentamicin, cardamom aqueous extracts (100 and 200 mg/kg, p.o.) significantly reduced the elevated serum levels of AST, ALT, bilirubin, cholesterol, triglycerides and low density lipoprotein cholesterol (LDL-chol) in gentamicin induced hepatotoxicity. Also cardamom aqueous extracts (100 &amp; 200 mg/kg, p.o.) significantly increased the lowered serum levels of albumin and high density lipoprotein cholesterol (HDL-chol) in gentamicin induced hepatotoxicity rats. Histopathological examination of the liver tissues supported the hepatoprotection. Our findings concluded that cardamom aqueous extracts possessed hepatoprotective activity against gentamicin induced hepatotoxicity in rats.</p>

scholarly journals A Novel Role of SIRT1/ FGF-21 in Taurine Protection Against Cafeteria Diet-Induced Steatohepatitis in Rats

2017 ◽  
Vol 43 (2) ◽  
pp. 644-659 ◽  
Author(s):  
Azza H. Abd Elwahab ◽  
Basma K. Ramadan ◽  
Mona F. Schaalan  ◽  
Amina M. Tolba
Keyword(s):  
Caspase 3 ◽  
B Cell Lymphoma ◽  
Cafeteria Diet ◽  
Control Group ◽  
Albino Rats ◽  
Protective Mechanism ◽  
Alcoholic Fatty Liver ◽  
Group I ◽  
Tnf Α

Background: Non-alcoholic fatty liver disease (NAFLD) is one of the alarmingly rising clinical problems in the 21st century with no effective drug treatment until now. Taurine is an essential amino acid in humans that proved efficacy as a non-pharmacological therapy in a plethora of diseases; however, its impact on NAFLD remains elusive. The aim of the current study is to evaluate the protective mechanism of taurine in experimental steatohepatitis induced by junk food given as cafeteria-diet (CAF-D) in male albino rats. Methods: Forty adult male albino rats of local strain between 8-10 weeks old, weighing 150 ± 20 g, were divided into four equal groups: Group I (control group), Group II (Taurine group), Group III (CAF-D for 12 weeks) and Group IV (CAF-D +Taurine). CAF-D was given in addition to the standard chow for 12 weeks, where each rat was given one piece of beef burger fried in 15 g of sunflower oil, one teaspoonful of mayonnaise, and one piece of petit pan bread, weighing 60g/ piece. In the serum, liver function tests; ALT, AST, ALP, GGT and the lipid profile; TG, TC, HDL-C added to reduced glutathione (GSH) were assessed colorimetrically, while fibroblast growth factor (FGF)-21, adiponectin & interleukin (IL)-6 via ELISA. The same technique was used for the assays of the hepatic levels of FGF-21, silent information regulator (SIRT1), malondialdehyde (MDA),IL-10, tumor necrosis factor-α (TNF-α) as well as the apoptotic markers; caspase-3 and B-cell lymphoma (Bcl-2). Results: The cafeteria-diet induced steatohepatitis was reflected by significantly increased body and liver weight gain, elevation of liver enzymes; ALT, AST, ALP and GGT added to the dyslipidemic panel, presented as increased TC, TG, LDL-C and decreased HDL-C levels. The steatosis-induced inflammatory milieu, marked by elevated serum levels of FGF-21, IL-6, hepatic TNF-α, as well as reduced IL-10 and adiponectin, was associated with steatosis- induced hepatic oxidative stress, reflected by increased hepatic MDA and decreased GSH levels, along with stimulated caspase-3 and decline in BcL-2 hepatic levels. These pathological disturbances were significantly ameliorated by taurine supplementation and evidenced histopathologically. The cross talk between hepatic FGF-21 and SIRT1 and their association to the induced perturbations are novel findings in this study. Taurine's efficacy in restoration of hepatic structure and function is partially via the increase in SIRT1 and associated reduction of FGF-21. Conclusion: The findings of the current study prove the protective role of taurine in NAFLD via a novel role in the amelioration of FGF-21/ SIRT1 axis, which could be considered a new therapeutic target.

scholarly journals Prophylactic and Therapeutic Effect of Aqueous Stem Extract of Costus afer on Lipids and Atherogenic Profile of Albino Rats in Acetaminophen Induced Liver Toxicity

2020 ◽  
pp. 16-24
Author(s):  
L. L. Nwisah ◽  
T - E. G. Davies ◽  
E. S. Bartimaeus
Keyword(s):  
Body Weight ◽  
Total Cholesterol ◽  
Liver Toxicity ◽  
Density Lipoprotein ◽  
Treatment Phase ◽  
Positive Control ◽  
Albino Rats ◽  
Therapeutic Effects ◽  
Stem Extract ◽  
Costus Afer

Background: Medicinal plants are widely used in Nigeria because they are believed to be effective in the treatment of various medical conditions and are also easily accessable with minimal side effect. Aim: This study evaluates the prophylactic and therapeutic effects of different doses (200 mg/kg, 400 mg/kg and 800 mg/kg body weight) of Costus afer on lipid profile of 50 male albino rats. Methodology: The research study was divided into 2 phases with 25 rats used for each phases. The 25 rats used for each phase were randomly selected into 5 groups with each group containing 5 rats. The rats used for the prophylactic phase were induced with 800 mg/kg body weight paracetamol for liver toxicity after administration of the various concentrations of aqueous stem extract of C. afer for 28 days while those used during the therapeutic phase were administered with the various concentrations of aqueous stem extract of C. afer following confirmation of liver toxicity using 800 mg/kg body weight acetaminophen. The effect of the aqueous extract was assessed by measuring the serum concentration of total cholesterol, triglycerides and high density lipoprotein using Randox reagent, while low density lipoprotein was calculated from the other parameters. Atherogenic ratios were also computed. The result obtained from the experiment was subjected to statistical analysis using Graph pad prism version 5.3 and values were considered significant at p<0.05. Results: Total cholesterol, triglycerides and LDL levels were significantly (p<0.05) reduced and HDL significantly increased in the treatment groups (prophylactic and therapeutic phases) compared to the positive control. When both phases were compared, total cholesterol and triglycerides showed significant (p<0.05) difference in concentration in groups fed with 400 mg/kg, 200 mgkg while LDL-C showed significant (p<0.05) variation between the two phases only at 400 mg/kg body weight. The extracts were also found to significantly (p<0.05) reduce the atherogenic status of the albino rats in both phases of treatment and between each treatment phase. Conclusion: Findings from this study suggest that Costus afer possesses the ability to regulate paracetamol induced dyslipidaemia and improve the anti-atherogenic status of treated albino rats.

scholarly journals Hepatotoxic Assessment of Tramadol-Diclofenac Use: A Study in a Rat Model

2019 ◽  
Vol 8 (2) ◽  
pp. 41-45
Author(s):  
Elias Adikwu ◽  
Ebinyo Clemente Nelson
Keyword(s):  
Density Lipoprotein ◽  
Serum Levels ◽  
The Body ◽  
Albino Rats ◽  
Gamma Glutamyl Transferase ◽  
Cholesterol Levels ◽  
Concurrent Use ◽  
Hepatotoxic Effect ◽  
Hepatocyte Necrosis ◽  
Glutamyl Transferase

The concurrent use of tramadol and diclofenac may increase hepatotoxic risk due to their individual hepatotoxic effects. This study assessed the hepatotoxic effect of tramadol-diclofenac administration in albino rats. Twenty-four adult male albino rats (200-220g) randomized into four groups were orally administered with tramadol (12mg/kg/day), diclofenac (6mg/kg/day) and tramadol-diclofenac for 14 days respectively. The rats were anesthetized, blood samples were collected and evaluated for serum liver function and lipid parameters. Liver samples were weighed and evaluated for biochemical parameters and histology. The effects of tramadol-diclofenac on the body and liver weights did not differ significantly (p>0.05) when compared to control. Also, effects were not significant (p>0.05) on blood glucose, and serum cholesterol, triglyceride, low and high density lipoprotein cholesterol levels when compared to control. Liver and serum levels of aminotransferases, alkaline phosphatase, lactate dehydrogenase, gamma–glutamyl transferase, conjugated bilirubin and total bilirubin increased significantly in rats treated with tramadol (p<0.05), diclofenac (p<0.01) and tramadol-diclofenac (p<0.001) when compared to control. Furthermore, significant decreases in liver catalase, glutathione, superoxide dismutase, glutathione peroxidase levels with significant increases in malondialdehyde levels occurred in rats treated with tramadol (p<0.05), diclofenac (p<0.01) and tramadol-diclofenac (p<0.001) when compared to control. Hepatocyte necrosis was observed in rats treated with tramadol-diclofenac. Tramadol-diclofenac may increase hepatotoxic risk at doses used for this study.

scholarly journals Guanxinkang Decoction Attenuates the Inflammation in Atherosclerosis by Regulating Efferocytosis and MAPKs Signaling Pathway in LDLR−/− Mice and RAW264.7 Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Yifan Zhang ◽  
Jie Ding ◽  
Yiru Wang ◽  
Xiaoteng Feng ◽  
Min Du ◽  
...  
Keyword(s):  
Western Blot ◽  
High Fat Diet ◽  
Caspase 3 ◽  
Density Lipoprotein ◽  
Treated Group ◽  
Raw264.7 Cells ◽  
Raw 264.7 Cells ◽  
High Fat ◽  
Phagocytic Ability ◽  
Tnf Α

Guanxinkang decoction (GXK), a traditional Chinese medicinal drug, is used to treat cardiovascular disease. The aim of the study was to investigate the effects of GXK on inflammation in LDLR−/− mice and RAW264.7 cells. Fed with high fat diet for 12 weeks, the mice were randomly divided into six groups, then administered with oral 0.9% saline or GXK (7.24, 14.48, and 28.96 g/kg) or Atorvastatin (1.3 mg/kg) for 12 weeks. RAW 264.7 cells were induced with ox-LDL or ox-LDL plus different concentrations of GXK (1.25, 2.5, and 5 μg/ml), or ox-LDL plus GXK plus MAPKs activators. Serum lipid profiles and inflammatory cytokines were detected by ELISA, gene expression by RT-qPCR, plaque sizes by Oil Red O, α-SMA, caspase 3, NF-κB p65 and TNF-α production by immunofluorescence staining, and protein expression by Western Blot. The phagocytic ability of cells was determined by neutral red uptake assay. Efferocytosis-related proteins (AML, MERTK, TYRO3 and MFGE8) and MAPKs pathways were detected by Western Blot. Compared to mice fed with high fat diet, the mice with GXK showed lower cholesterol, triglyceride, low-density lipoprotein cholesterol, IL-1β, IL-6, and TNF-α, smaller plaque sizes, higher α-SMA, and lower caspase 3 and NF-κB p65 in aortic roots. RAW264.7 cells treated with ox-LDL plus GXK had lower IL-1β, IL-6, and TNF-α. GXK also increased the phagocytic ability of cells. High levels of AML, MERTK, TYRO3 and MFGE8, and decreased levels of iNOS, VCAM-1, LOX-1 and MCP-1, and phosphorylation of ERK1/2, JNK, p38, and NF-κB were detected in GXK-treated group. MAPKs activators reversed the effects of GXK in repressing inflammation and promoting phagocytosis. These results suggested that GXK could attenuate atherosclerosis and resolve inflammation via efferocytosis and MAPKs signaling pathways in LDLR−/− mice and RAW264.7 cells.

scholarly journals Geraniol Averts Methotrexate-Induced Acute Kidney Injury via Keap1/Nrf2/HO-1 and MAPK/NF-κB Pathways

2021 ◽  
Vol 43 (3) ◽  
pp. 1741-1755
Author(s):  
Nancy S. Younis ◽  
Heba S. Elsewedy ◽  
Tamer M. Shehata ◽  
Maged E. Mohamed
Keyword(s):  
Acute Kidney Injury ◽  
Caspase 3 ◽  
Kidney Injury ◽  
Serum Levels ◽  
Treated Group ◽  
Histopathological Changes ◽  
Tnf Α ◽  
Autoimmune Conditions ◽  
Antioxidant Parameters ◽  
Natural Monoterpene

Objectives: Geraniol, a natural monoterpene, is an essential oil component of many plants. Methotrexate is an anti-metabolite drug, used for cancer and autoimmune conditions; however, clinical uses of methotrexate are limited by its concomitant renal injury. This study investigated the efficacy of geraniol to prevent methotrexate-induced acute kidney injury and via scrutinizing the Keap1/Nrf2/HO-1, P38MAPK/NF-κB and Bax/Bcl2/caspase-3 and -9 pathways. Methods: Male Wister rats were allocated into five groups: control, geraniol (orally), methotrexate (IP), methotrexate and geraniol (100 and 200 mg/kg). Results: Geraniol effectively reduced the serum levels of creatinine, urea and Kim-1 with an increase in the serum level of albumin when compared to the methotrexate-treated group. Geraniol reduced Keap1, escalated Nrf2 and HO-1, enhanced the antioxidant parameters GSH, SOD, CAT and GSHPx and reduced MDA and NO. Geraniol decreased renal P38 MAPK and NF-κB and ameliorated the inflammatory mediators TNF-α, IL-1β, IL-6 and IL-10. Geraniol negatively regulated the apoptotic mediators Bax and caspase-3 and -9 and increased Bcl2. All the biochemical findings were supported by the alleviation of histopathological changes in kidney tissues. Conclusion: The current findings support that co-administration of geraniol with methotrexate may attenuate methotrexate-induced acute kidney injury.

The protective and therapeutic effects of linalool against doxorubicin-induced cardiotoxicity in Wistar albino rats

2019 ◽  
Vol 38 (7) ◽  
pp. 803-813 ◽  
Author(s):  
Z Oner ◽  
E Altınoz ◽  
H Elbe ◽  
N Ekinci
Keyword(s):  
Caspase 3 ◽  
Inflammatory Cell ◽  
Cardiac Tissue ◽  
Saline Solution ◽  
Albino Rats ◽  
Therapeutic Effects ◽  
Histopathological Changes ◽  
Treatment Groups ◽  
Wistar Albino Rats ◽  
Plasma Creatine Kinase

The aim of the present study was to determine the protective and therapeutic effects of linalool (LIN) against doxorubicin (DOX)-induced cardiotoxicity in rats histologically and biochemically. In experiments, 64 male Wistar albino rats were randomly divided into eight groups ( n = 8). These groups were control (C) (0.9% saline solution), DOX (20 mg/kg DOX), LIN50 (50 mg/kg LIN), LIN100 (100 mg/kg LIN), DOX + LIN50 (20 mg/kg DOX and 50 mg/kg LIN), DOX + LIN100 (20 mg/kg DOX and 100 mg/kg LIN), LIN50 + DOX (50 mg/kg LIN and 20 mg/kg DOX), and LIN100 + DOX (100 mg/kg LIN and 20 mg/kg DOX). It was determined that necrosis and extensive inflammatory cell infiltration were observed in the DOX group. It was determined that histopathological changes significantly decreased in groups treated with LIN after DOX administration. While the caspase-3 immunostaining was highly evident in DOX group apoptotic cells ( p < 0.001, for all), the intensity of caspase-3 immunostaining in the treatment groups decreased ( p < 0.05). While DOX administration resulted in a significant increase in malondialdehyde (MDA) levels and plasma Creatine kinase (CK) and lactate dehydrogenase (LDH) levels in cardiac tissue when compared to the C groups, it was observed that DOX + LIN administration led to a significant decrease in MDA, plasma CK and LDH levels and a significant increase in glutathione (GSH), superoxide dismutase, and catalase enzyme levels. Finally, it was concluded that DOX led to heavy cardiotoxicity and DOX + LIN administration could remove cardiomyopathy symptoms.

Paricalcitol pretreatment attenuates renal ischemia/reperfusion injury by inhibiting p38 MAPK and activating PI3K/Akt signaling pathways

2019 ◽  
Vol 44 (4) ◽  
pp. 452-461
Author(s):  
Zahide Cavdar ◽  
Cemre Ural ◽  
Ayse Kocak ◽  
Sevki Arslan ◽  
Sibel Ersan ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
P38 Mapk ◽  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Akt Signaling ◽  
Albino Rats ◽  
Sod Activity ◽  
Interstitial Inflammation ◽  
Tnf Α ◽  
Active Caspase

Abstract Objective This study aimed to investigate the renoprotective effects of paricalcitol, a synhetic vitamin D analog, through its possible roles on p38 MAPK and PI3K/Akt signaling pathways to prevent oxidative stress, inflammation and apoptosis during renal I/R. Materials and methods Total 20 kidney tissues of sham (n = 6), subjected to renal I/R bilaterally for 45 min ischemia followed by 24 h reperfusion (n = 7) and paricalcitol (0.3 μg/kg, ip) pretreated Wistar albino rats (n =7) were used in this study. Interstitial inflammation and active caspase-3 expression were evaluated histologically. TNF-α, IL-1β, kidney injury molecule-1 (KIM-1), MDA and SOD activity in kidneys were analysed biochemically. Furthermore, activation of p38 MAPK, PI3K/Akt signaling pathways and NFκB p65 were evaluated by western blot. Results Paricalcitol pretreatment significantly reduced interstitial inflammation during renal I/R, which was consistent with decreased tumor TNF-α, IL-1β, active caspase-3 and KIM-1 expression. Paricalcitol also reduced MDA level and attenuated the reduction of SOD activity in the kidney during I/R. Moreover, paricalcitol could suppress the p38 MAPK and NFκB p65, and also activate PI3K/Akt signaling pathway during renal I/R. Conclusion All these findings indicate that paricalcitol may be an effective practical strategy to prevent renal I/R injury.

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