Limits...
Mitochondrial modulation by Epigallocatechin 3-Gallate ameliorates cisplatin induced renal injury through decreasing oxidative/nitrative stress, inflammation and NF-kB in mice.

Pan H, Chen J, Shen K, Wang X, Wang P, Fu G, Meng H, Wang Y, Jin B - PLoS ONE (2015)

Bottom Line: The aim of this study is to investigate whether Epigallocatechin 3-Gallate (EGCG) can reduce cisplatin mediated side effect in kidney and to understand its mechanism of protection against tissue injury.As a result, EGCG improved renal function in cisplatin mediated kidney damage.Thus, our data suggest that EGCG may represent new promising adjunct candidate for cisplatin.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

ABSTRACT
Cancer chemotherapy drug cisplatin is known for its nephrotoxicity. The aim of this study is to investigate whether Epigallocatechin 3-Gallate (EGCG) can reduce cisplatin mediated side effect in kidney and to understand its mechanism of protection against tissue injury. We used a well-established 3-day cisplatin induced nephrotoxicity mice model where EGCG were administered. EGCG is a major active compound in Green Tea and have strong anti-oxidant and anti-inflammatory properties. EGCG protected against cisplatin induced renal dysfunction as measured by serum creatinine and blood urea nitrogen (BUN). EGCG improved cisplatin induced kidney structural damages such as tubular dilatation, cast formation, granulovaculoar degeneration and tubular cell necrosis as evident by PAS staining. Cisplatin induced kidney specific mitochondrial oxidative stress, impaired activities of mitochondrial electron transport chain enzyme complexes, impaired anti-oxidant defense enzyme activities such as glutathione peroxidase (GPX) and manganese superoxide dismutase (MnSOD) in mitochondria, inflammation (tumor necrosis factor α and interleukin 1β), increased accumulation of NF-κB in nuclear fraction, p53 induction, and apoptotic cell death (caspase 3 activity and DNA fragmentation). Treatment of mice with EGCG markedly attenuated cisplatin induced mitochondrial oxidative/nitrative stress, mitochondrial damages to electron transport chain activities and antioxidant defense enzyme activities in mitochondria. These mitochondrial modulations by EGCG led to protection mechanism against cisplatin induced inflammation and apoptotic cell death in mice kidney. As a result, EGCG improved renal function in cisplatin mediated kidney damage. In addition to that, EGCG attenuated cisplatin induced apoptotic cell death and mitochondrial reactive oxygen species (ROS) generation in human kidney tubular cell line HK-2. Thus, our data suggest that EGCG may represent new promising adjunct candidate for cisplatin.

No MeSH data available.


Related in: MedlinePlus

Schematic diagram of protection mechanism of EGCG in cisplatin induced kidney injury.EGCG inhibit cisplatin induced mitochondrial ROS (Reactive Oxygen Species) in the renal tubular cells which caused cell death. Cell death in the tubular cells leads to pro-inflammatory response with cytokines (TNFα and IL1β). These process leads to leukocytes infiltration with additional burst of oxidative stress. EGCG also neutralize these pro-inflammatory cytokines. All combinatorial effects leads to reduced inflammation and cell death, thus protecting against cisplatin induced kidney injury.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4398485&req=5

pone.0124775.g009: Schematic diagram of protection mechanism of EGCG in cisplatin induced kidney injury.EGCG inhibit cisplatin induced mitochondrial ROS (Reactive Oxygen Species) in the renal tubular cells which caused cell death. Cell death in the tubular cells leads to pro-inflammatory response with cytokines (TNFα and IL1β). These process leads to leukocytes infiltration with additional burst of oxidative stress. EGCG also neutralize these pro-inflammatory cytokines. All combinatorial effects leads to reduced inflammation and cell death, thus protecting against cisplatin induced kidney injury.

Mentions: Briefly, in this study we demonstrated EGCG protects again cisplatin induced renal injury through mitochondrial protection in three ways (1) by improving cisplatin induced mitochondrial electron chain complexes, (2) by improving mitochondrial antioxidant function in enzymes MnSOD and GPX, (3) improving cisplatin induced mitochondrial oxidative/nitrative damage and (4) anti-inflammatory effect (Fig 9). Here, we also demonstrated that EGCG reduced cisplatin induced inflammatory response by lowering pro-inflammatory cytokines and neutrophil infiltration. EGCG also modulated cisplatin induced nuclear translocation of NFκB (p65), which has role in inflammation and oxidative stress. Another transcription factor p53, DNA damage response factor, also modulated by EGCG in cisplatin affected tubular cells. This modulation lead to improvement of cisplatin induced DNA fragmentation and Caspase activity or apoptosis by EGCG in renal tissue. These protective effects of EGCG, also a natural ingredient of Green Tea, will be very useful for therapeutic purpose in cisplatin induced kidney injury or other kidney injury models where mitochondria/oxidative stress/inflammation is involved. It is important to note that EGCG is reported to be effective against various cancer [60–64] and this will make is ideal adjunct candidate for cisplatin chemotherapy.


Mitochondrial modulation by Epigallocatechin 3-Gallate ameliorates cisplatin induced renal injury through decreasing oxidative/nitrative stress, inflammation and NF-kB in mice.

Pan H, Chen J, Shen K, Wang X, Wang P, Fu G, Meng H, Wang Y, Jin B - PLoS ONE (2015)

Schematic diagram of protection mechanism of EGCG in cisplatin induced kidney injury.EGCG inhibit cisplatin induced mitochondrial ROS (Reactive Oxygen Species) in the renal tubular cells which caused cell death. Cell death in the tubular cells leads to pro-inflammatory response with cytokines (TNFα and IL1β). These process leads to leukocytes infiltration with additional burst of oxidative stress. EGCG also neutralize these pro-inflammatory cytokines. All combinatorial effects leads to reduced inflammation and cell death, thus protecting against cisplatin induced kidney injury.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4398485&req=5

pone.0124775.g009: Schematic diagram of protection mechanism of EGCG in cisplatin induced kidney injury.EGCG inhibit cisplatin induced mitochondrial ROS (Reactive Oxygen Species) in the renal tubular cells which caused cell death. Cell death in the tubular cells leads to pro-inflammatory response with cytokines (TNFα and IL1β). These process leads to leukocytes infiltration with additional burst of oxidative stress. EGCG also neutralize these pro-inflammatory cytokines. All combinatorial effects leads to reduced inflammation and cell death, thus protecting against cisplatin induced kidney injury.
Mentions: Briefly, in this study we demonstrated EGCG protects again cisplatin induced renal injury through mitochondrial protection in three ways (1) by improving cisplatin induced mitochondrial electron chain complexes, (2) by improving mitochondrial antioxidant function in enzymes MnSOD and GPX, (3) improving cisplatin induced mitochondrial oxidative/nitrative damage and (4) anti-inflammatory effect (Fig 9). Here, we also demonstrated that EGCG reduced cisplatin induced inflammatory response by lowering pro-inflammatory cytokines and neutrophil infiltration. EGCG also modulated cisplatin induced nuclear translocation of NFκB (p65), which has role in inflammation and oxidative stress. Another transcription factor p53, DNA damage response factor, also modulated by EGCG in cisplatin affected tubular cells. This modulation lead to improvement of cisplatin induced DNA fragmentation and Caspase activity or apoptosis by EGCG in renal tissue. These protective effects of EGCG, also a natural ingredient of Green Tea, will be very useful for therapeutic purpose in cisplatin induced kidney injury or other kidney injury models where mitochondria/oxidative stress/inflammation is involved. It is important to note that EGCG is reported to be effective against various cancer [60–64] and this will make is ideal adjunct candidate for cisplatin chemotherapy.

Bottom Line: The aim of this study is to investigate whether Epigallocatechin 3-Gallate (EGCG) can reduce cisplatin mediated side effect in kidney and to understand its mechanism of protection against tissue injury.As a result, EGCG improved renal function in cisplatin mediated kidney damage.Thus, our data suggest that EGCG may represent new promising adjunct candidate for cisplatin.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

ABSTRACT
Cancer chemotherapy drug cisplatin is known for its nephrotoxicity. The aim of this study is to investigate whether Epigallocatechin 3-Gallate (EGCG) can reduce cisplatin mediated side effect in kidney and to understand its mechanism of protection against tissue injury. We used a well-established 3-day cisplatin induced nephrotoxicity mice model where EGCG were administered. EGCG is a major active compound in Green Tea and have strong anti-oxidant and anti-inflammatory properties. EGCG protected against cisplatin induced renal dysfunction as measured by serum creatinine and blood urea nitrogen (BUN). EGCG improved cisplatin induced kidney structural damages such as tubular dilatation, cast formation, granulovaculoar degeneration and tubular cell necrosis as evident by PAS staining. Cisplatin induced kidney specific mitochondrial oxidative stress, impaired activities of mitochondrial electron transport chain enzyme complexes, impaired anti-oxidant defense enzyme activities such as glutathione peroxidase (GPX) and manganese superoxide dismutase (MnSOD) in mitochondria, inflammation (tumor necrosis factor α and interleukin 1β), increased accumulation of NF-κB in nuclear fraction, p53 induction, and apoptotic cell death (caspase 3 activity and DNA fragmentation). Treatment of mice with EGCG markedly attenuated cisplatin induced mitochondrial oxidative/nitrative stress, mitochondrial damages to electron transport chain activities and antioxidant defense enzyme activities in mitochondria. These mitochondrial modulations by EGCG led to protection mechanism against cisplatin induced inflammation and apoptotic cell death in mice kidney. As a result, EGCG improved renal function in cisplatin mediated kidney damage. In addition to that, EGCG attenuated cisplatin induced apoptotic cell death and mitochondrial reactive oxygen species (ROS) generation in human kidney tubular cell line HK-2. Thus, our data suggest that EGCG may represent new promising adjunct candidate for cisplatin.

No MeSH data available.


Related in: MedlinePlus