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INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS Daniel Saldarriaga Melissa Zapata III SEMESTER –MEDICINE UPB Satoru Mitazaki, Shigeyoshi Honma, Minwako Suto, Naho Kato, Kouichi Haraiwa, Makoto Yoshida, Sumiko Abe

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Page 1: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL

FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

Daniel Saldarriaga

Melissa Zapata

III SEMESTER –MEDICINE

UPB

Satoru Mitazaki, Shigeyoshi Honma, Minwako Suto, Naho Kato, Kouichi Haraiwa, Makoto Yoshida, Sumiko Abe

Page 2: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

INTRODUCTION

Page 3: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

INTRODUCTION

Function is to regulate events such as activation, differentiation

or proliferation, antibody secretion, chemotaxis, regulation of cytokines

and other factors.

Synthesized primarily by leukocytes or endothelial cells, stromal thymus or

bone marrow.

Set of proteins that act as chemical

messengers within walking distance.

INTERLEUKIN

Page 4: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

INTRODUCTION

Is a glycoprotein

Secreted by macrophages, T cells, endothelial cells and fibroblasts

inflammatory and proinflammatory activity

Involved in the production of immunoglobulins

the differentiation of B cells, activated cytotoxic T lymphocytes, plasma cells, modulates hematopoiesis and fibrinógeno

IL-6 with IL1 act with proteins in the acute phase

INTERLEUKIN-6

Page 5: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

INTRODUCTION

Abrupt and sustained deterioration

of glomerular filtration expressed

initially by inability to excrete nitrogenous

products and a tendency to oliguria

Has a high mortality - on average 50%

Page 6: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

INTRODUCTION

Alterations of the glomerular filtration

Intrarenal vasoconstriction

Tubular lumen obstruction

Backscatter glomerular filtration

rate

CAUSES

Page 7: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

INTRODUCTION

Oxidative stress is caused by an imbalance between production of reactive

oxygen and the ability of a biological system to

detoxify reactive intermediates or quickly repa

ir the damage resulting.

OXIDATIVE STRESS

Page 8: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

Can cause toxic effects through the production of

peroxides and free radicals that damage all

components of the cell, including proteins, lipids

and DNA.

INTRODUCTION

Page 9: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

INTRODUCTION

BAD HABITS ALIMENTICION

STRESSSMOKE SNUFF

RADIATIONALCOHOL

DEPRESSIONASIEDAD SEDENTARY

Page 10: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

INTRODUCTION

Platinum-based drug used in

chemotherapy to treat various types of

cancer, which include sarcomas, some

carcinomas lymphomas and germ cell tumor

CISPLATIN

Page 11: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

CORRELATION

Page 12: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

OBJECTIVE

Page 13: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

MAIN OBJETIVE

Asses the role of the interleukin-6 like a

protective factor in acute renal failure through some experiment, to check the

hypotesis

Page 14: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

MATERIALES Y METODOS

Page 15: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

MATERIALES Y METODOS

ANIMALES

ACCION DE LA IL – 6 KNOCKOUTSIMULACION DEL HUMANO

Page 16: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

MATERIALES Y METODOS

WESTERN BLOTTING

DETECTA PROTEINAS ESPECIFICAS POR ELECTROFORESIS EN GEL.

Page 17: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

MATERIALES Y METODOS

INMUNOHISTOQUIMICA

METODO QUE UTILIZA DE ANTICUERPOS ESPECIFICOS APLICADA A UN TEJIDO

Page 18: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

MATERIALES Y METODOS

PCR TIEMPO REAL

Amplificar y cuantificar a la misma ves producto de la amplificación ADN

Page 19: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

RESULTADOS

Page 20: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

RESULTADOS

• Fig 1

Page 21: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

RESULTADOS

• Fig 3

Page 22: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

RESULTADOS

• Fig 5

Page 23: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

RESULTADOS

• Fig 6

Page 24: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

DISCUSSION

Page 25: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

RESEARCHER ENDS YES NO

Mitazaki et al., 2009 IL-6 produced in renal tubular cells is thought to prevent progression of acute renal failure at the early stage.

Matsushima et al., 1998 lameire et al., 2005

IL-6 plays a protective role in the development of cisplatin- induced acute renal failure through upregulation of anti-oxidativ stress factors.

Page 26: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

RESEARCHER ENDS YES

NO

Dixit et al., 2009 Increase of A-HNE modified prteins is commonly used as an indicator of lipid peroxidationt. Therefore, lack of IL-6 migh be responsible for the iincrease of lipid peroxidation.

James et al., 2005 Unregulated cox-2 expression and prostaglandin synthesis influence inflammation

Page 27: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

CONCLUSIONS

Page 28: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

CONCLUSIONS

Such activities promote student skills in developing experimental and innovative research to generate awareness investigative.

It is important to apply the findings to clinical practice, because they feed the knowledge learned in formal education.

Page 29: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

CONCLUSIONS

The current development of medicine has been marked by many discoveries about the metabolic function of cells and the development of multiple types of analysis in biological samples, these are of great importance of medical diagnostic.

Page 30: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

CONCLUSIONS

The importance of molecular biomarkers such as IL-6, the protective acute renal failure are useful elements for its association to diseases.

Page 31: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

Daniel Saldarriaga Arango

Page 32: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

Melissa Zapata Durán

Page 33: INTERLEUKIN-6 PLAYS A PROTECTIVE ROLE IN DEVELOPMENT OF CISPLATIN-INDUCED ACUTE RENAL FAILURE THROUGH UPREGULATION OF ANTI-OXIDATIVE STRESS FACTORS

THANKS!