Protective effects of chitosan oligosaccharide on paraquat-induced nephrotoxicity in rats Byung Chul Shin, Wan Soo Lee, Dae Wong Kang, Jong Hoon Chung.

Slides:



Advertisements
Similar presentations
Caspase Activity in Apoptotic Cells Cell Bio 220 Tenzin Dolkar Stephanie Kim Victoire Ndong Patricia Wong.
Advertisements

Apoptosis, controlled cell death, is a natural process of development. Recently it has been found that mitochondria play an important role in apoptosis.
Isosteviol derivatives induced apoptosis in Human lung cancer via targeting MEK/MAPK pathway: An in vitro and in vivo study Ahmed M Malki 1,,PhD Stephen.
Development of Western Blots for Actin without the use of radioactivity Geoff Theobald STEP Summer Internship Program June 2003.
Eun Chul Kim, M.D., Man Soo Kim, M.D. Department of Ophthalmology & Visual Science, College of Medicine, Catholic University of Korea, Seoul, Korea The.
Probiotic Bacteria Prevent Gut Permeability During Heat Stress Iryna Sorokulova, Ludmila Globa, Oleg Pustovyy, Vitaly Vodyanoy Department of Anatomy, Physiology.
Neuroprotective Effects of Bone Marrow Stromal Cell Transplantation in Combination With Treadmill Exercise Following Traumatic Brain Injury Mal Soon Shin.
International Neurourology Journal 2014;18:
International Neurourology Journal 2014;18:
Inhibition of autophagy augments 5-fluorouracil chemotherapy in human colon cancer in vitro and in vivo model  Jie Li, Ni Hou, Ahmad Faried, Soichi Tsutsumi,
Volume 124, Issue 7, Pages (June 2003)
Takehiko Wada, Jeffrey W. Pippin, Yoshio Terada, Stuart J. Shankland 
Cx43 Mediates Resistance against MPP+ -Induced
Pentoxifylline Alleviates Perinatal Hypoxic-Ischemia-Induced Short-term Memory Impairment by Suppressing Apoptosis in the Hippocampus of Rat Pups Je Hoon.
The Combined Effects of Hematoporphyrin Monomethyl Ether-SDT and Doxorubicin on the Proliferation of QBC939 Cell Lines  Lei Liang, Sheng Xie, Lin Jiang,
E. Homsi, P. Janino, J.B.L. de Faria  Kidney International 
International Neurourology Journal 2014;18:77-85
Induction of Apoptosis by Ethanol Extracts of Ganoderma lucidum in Human Gastric Carcinoma Cells  Kyung-Jun Jang, Min-Ho Han, Byung-Hoon Lee, Byung-Woo.
Volume 139, Issue 2, Pages (August 2010)
Volume 85, Issue 3, Pages (March 2014)
Volume 19, Issue 7, Pages (July 2017)
The Chemopreventive Effect of Tanacetum Polycephalum Against LA7-Induced Breast Cancer in Rats and the Apoptotic Effect of a Cytotoxic Sesquiterpene.
Volume 76, Issue 8, Pages (October 2009)
Volume 79, Issue 2, Pages (January 2011)
Jinu Kim, Kelly E. Long, Kang Tang, Babu J. Padanilam 
Volume 25, Issue 4, Pages (April 2014)
Volume 72, Issue 4, Pages (August 2007)
Anti-apoptotic effect of transforming growth factor-β1 on human articular chondrocytes: role of protein phosphatase 2A  M. Lires-Deán, B.S., B. Caramés,
C.B. Marshall, J.W. Pippin, R.D. Krofft, S.J. Shankland 
Volume 71, Issue 10, Pages (May 2007)
Volume 147, Issue 4, Pages (October 2014)
Volume 62, Issue 1, Pages (July 2002)
Volume 138, Issue 4, Pages e3 (April 2010)
Genistein protects the kidney from cisplatin-induced injury
Volume 73, Issue 5, Pages (March 2008)
Volume 126, Issue 1, Pages (January 2004)
Volume 60, Issue 3, Pages (September 2001)
Uc.454 Inhibited Growth by Targeting Heat Shock Protein Family A Member 12B in Non- Small-Cell Lung Cancer  Jun Zhou, Chenghai Wang, Weijuan Gong, Yandan.
Volume 73, Issue 4, Pages (February 2008)
Leptin promotes apoptosis and inhibits autophagy of chondrocytes through upregulating lysyl oxidase-like 3 during osteoarthritis pathogenesis  Z.M. Huang,
Inhibiting MDM2-p53 Interaction Suppresses Tumor Growth in Patient-Derived Non– Small Cell Lung Cancer Xenograft Models  Josephine Hai, PhD, Shingo Sakashita,
Volume 78, Issue 2, Pages (July 2010)
Autophagy in proximal tubules protects against acute kidney injury
Volume 24, Issue 9, Pages (September 2016)
BV6, an IAP Antagonist, Activates Apoptosis and Enhances Radiosensitization of Non- small Cell Lung Carcinoma In Vitro  Wenyan Li, MD, PhD, Bo Li, MD,
Rafael Gongora, Robert P Stephan, Zhixin Zhang, Max D Cooper  Immunity 
Role of meprin A in renal tubular epithelial cell injury
Volume 77, Issue 4, Pages (February 2010)
Volume 73, Issue 5, Pages (March 2008)
Renal L-type fatty acid-binding protein mediates the bezafibrate reduction of cisplatin- induced acute kidney injury  K. Negishi, E. Noiri, R. Maeda, D.
Youry Kim, Jenny L. Anderson, Sharon R. Lewin  Cell Host & Microbe 
Activation of Akt as a Mechanism for Tumor Immune Evasion
Volume 57, Issue 3, Pages (March 2000)
Molecular Therapy - Nucleic Acids
Volume 41, Issue 6, Pages (December 2004)
Glucosamine sulfate modulates the levels of aggrecan and matrix metalloproteinase-3 synthesized by cultured human osteoarthritis articular chondrocytes 
Volume 77, Issue 8, Pages (April 2010)
Volume 19, Issue 5, Pages (November 2003)
Role of NF-κB Activity in Apoptotic Response of Keratinocytes Mediated by Interferon-γ, Tumor Necrosis Factor-α, and Tumor-Necrosis-Factor-Related Apoptosis-Inducing.
The pathological role of Bax in cisplatin nephrotoxicity
Arsenic Induces Tumor Necrosis Factor α Release and Tumor Necrosis Factor Receptor 1 Signaling in T Helper Cell Apoptosis  Hsin-Su Yu, Gwo-Shing Chen 
Volume 76, Issue 7, Pages (October 2009)
Volume 72, Issue 8, Pages (October 2007)
Syed M. Meeran, Thejass Punathil, Santosh K. Katiyar 
Volume 39, Issue 6, Pages (December 2003)
Volume 19, Issue 11, Pages (June 2017)
Volume 41, Issue 5, Pages (November 2004)
MEK inhibitor, U0126, attenuates cisplatin-induced renal injury by decreasing inflammation and apoptosis  Sang-Kyung Jo, Won Yong Cho, Su Ah Sung, Hyoung.
Volume 56, Issue 6, Pages (December 1999)
E. Homsi, P. Janino, J.B.L. de Faria  Kidney International 
Presentation transcript:

Protective effects of chitosan oligosaccharide on paraquat-induced nephrotoxicity in rats Byung Chul Shin, Wan Soo Lee, Dae Wong Kang, Jong Hoon Chung and Hyun Lee Kim Division of Nephrology, Department of Internal Medicine, College of Medicine, Chosun University Protective effects of chitosan oligosaccharide on paraquat-induced nephrotoxicity in rats Byung Chul Shin, Wan Soo Lee, Dae Wong Kang, Jong Hoon Chung and Hyun Lee Kim Division of Nephrology, Department of Internal Medicine, College of Medicine, Chosun University Introduction Paraquat (PQ; 1,1'-dimethyl-4,4'-bipyridinium dichloride) - world wide used herbicide and has a very high mortality rate in human Chitosans - N-deacylated derivative of chitin in crab and shrimp shells - Physiological activities : antitumor activities, immuno-enhancing effect, ant-micorbial effect, cholesterol reducing effect and antioxidant effects. Apoptosis PUMA (p53 upregulated modulator of apoptosis): pro-apoptotic member of the Bcl-2 protein family and induction of programmed cell death 6). [ [ APE (Apurinic/apyrimidinic endonuclease): repair of DNA damage and inhibits pro-apoptotic functions of P53 7). Caspse-3: important role in the apoptotic process in two ways 8). First: apoptotic gene PUMA and an effector of the caspase cascade, caspase-3, were evaluated to gain insight into apoptotic signaling during PQ- induced nephrotoxicity. Second,: protective effects of COS were estimated through restoration of serological parameters and by PUMA and caspase-3 expression. Finally: roles of apurinic/apyrimidinic endonuclease (APE) were also as- 103 sessed in PQ-induced nephrotoxicity. RatsMice Male Sprague–Dawley rats (8–10 weeks old, 200–250 g) Experimental protocol Western Blot electrophoresed on 10% SDS–PAGE gels transferred to polyvinyldifluoridine membranes (GE, Healthcare Bio- Sciences Corp., Piscataway, NJ). detected using the iNtRON Biotech Enhanced Chemiluminescence Detect System (Seoul, Republic of Korea) and quantified using ImageQuant 350 (GE Healthcare Korea, Seoul, Republic of Korea) densitometric units of each primary antibody relative to b-actin and in reference to the value of the control sample for each gel. Cytoarchitecture and Immunohistochemistry 5-lm-thick serial sections were cut using a Leica RM2155 rotary microtome (Nussloch, Germany) and mounted on slides coated with 3-aminopropyl-tri- ethoxy-silane (Sigma–Aldrich, St. Louis, MO). Immunohistochemical staining was carried out by the routine method. Statistical analysis analyzed using Mann–Whitney test and Kruskal–Wallis test (SPSS version 11.0, Chicago, IL, USA). A p value of less than 0.05 was considered significant. Body weight and serological aspects Methods Results-2 Purpose Western blot analysis Western blot analysis of apurinic/apyrimidinic endonuclease (APE), p53-upregulated modulator of apoptosis (PUMA), caspase-3, and cleaved caspase- 3 expression in the kidneys of paraquat (PQ)-intoxicated rats. The levels of these proteins increased in a time-dependent manner in the control group after PQ administration. Pretreatment with chitosan oligosaccharide (COS) resulted in a higher level of these proteins before PQ injection, which decreased at the end of experiment. Densitometric results in the control and chitosan oligosaccharide (COS) groups in paraquat (PQ)-intoxicated rats. Changes are compared bewteen groups at the same time point. *p < 0.05; #p = 0.05; Cas-3, caspase-3; Cl. Cas-3, cleaved caspase-3. Histology (PAS stain) Immunohistochemistry PQ concentration, BUN/s-Cr level -Significantly increased in PQ group and decreased in COS-PQ group with time dependant manner (p<0.05). Caspase-3 and PUMA protein expression -Significantly increased in PQ group and decreased after 24hours in COS-PQ group compared with PQ group. APE protein expression -Significantly increased after 12hours in COS-PQ group compared with PQ group. PQ induced apoptosis via elevated cleaved caspase-3 and PUMA in the rat kidneys, which might contribute to the clinical manifestations of PQ intoxication. COS had renoprotective effects on PQ-induced nephrotoxicity by suppressing apoptosis and increasing anti-renin activity following an increase in APE. This study has provided supporting evidence for the renoprotective effects of COS in PQ-induced nephrotoxicity, suggesting that it may be a potential aid to manage patients suffering from PQ intoxication. Periodic acid Schiff (PAS) staining in the deep renal cortex in paraquat (PQ)-intoxicated rats. It clearly shows the proximal convoluted tubules in both groups ((A) control group; (C) chitosan oligosaccharide (COS) group) before PQ injection and also shows that the findings had disappeared 24 h after PQ administration (B). Only a few proximal tubules bear brush borders (asterisks). COS pretreatment prevented the degenerative changes in proximal tubules (D), whereas the distal tubules and collecting ducts were not affected by PQ administration. Scale bar = 50 um. Immunohistochemistry with apurinic/apyrimidinic endonuclease (APE) (upper column) and cleaved caspase-3 (lower column) in the kidneys of paraquat (PQ)-intoxicated rats. APE and cleaved caspase-3 were mainly seen in the proximal tubules of the control renal cortex. They were found in whole components of nephrons from 4 h after PQ injection, but degenerated proximal tubules (asterisks) were devoid of immunoreactivity 24 h after PQ injection. Chitosan oligosaccharide (COS)-pretreated kidneys showed ubiquitous distribution of immunolocalized APE and cleaved caspase-3. The immunolocalization did not change until 24 h after PQ injection, even in the proximal convoluted tubules. G, glomeruli. Scale bar = 100 um. Results-1 SummarySummary ConclusionConclusion