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Modulation of endoplasmic reticulum stress and cardiomyocyte apoptosis by mulberry leaf diet in experimental autoimmune myocarditis rats.

Arumugam S, Thandavarayan RA, Veeraveedu PT, Ma M, Giridharan VV, Arozal W, Sari FR, Sukumaran V, Lakshmanan A, Soetikno V, Suzuki K, Kodama M, Watanabe K - J Clin Biochem Nutr (2011)

Bottom Line: Mulberry is commonly used as silkworm diet and an alternative medicine in Japan and China, has recently reported to contain many antioxidative flavanoid compounds and having the free radical scavenging effects.Antioxidants reduce cardiac oxidative stress and attenuate cardiac dysfunction in animals with pacing-induced congestive heart failure.ML significantly decreased oxidative stress, myocyte apoptosis, cellular infiltration, cardiac fibrosis, mast cell density, myocardial levels of sarco/endo-plasmic reticulum Ca(2+) ATPase2, p22(phox), receptor for advanced glycation end products, phospho-p38 mitogen activated protein kinase, phospho-c-Jun NH(2)-terminal protein kinase, glucose regulated protein78, caspase12 and osteopontin levels in EAM rats.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, 265-1 Higashizima, Akiha-ku, Niigata 956-8603, Japan.

ABSTRACT
Mulberry is commonly used as silkworm diet and an alternative medicine in Japan and China, has recently reported to contain many antioxidative flavanoid compounds and having the free radical scavenging effects. Antioxidants reduce cardiac oxidative stress and attenuate cardiac dysfunction in animals with pacing-induced congestive heart failure. Hence we investigated the cardioprotective effect of mulberry leaf powder in rats with experimental autoimmune myocarditis. Eight-week-old Lewis rats immunized with cardiac myosin were fed with either normal chow or a diet containing 5% mulberry leaf powder and were examined on day 21. ML significantly decreased oxidative stress, myocyte apoptosis, cellular infiltration, cardiac fibrosis, mast cell density, myocardial levels of sarco/endo-plasmic reticulum Ca(2+) ATPase2, p22(phox), receptor for advanced glycation end products, phospho-p38 mitogen activated protein kinase, phospho-c-Jun NH(2)-terminal protein kinase, glucose regulated protein78, caspase12 and osteopontin levels in EAM rats. These results may suggest that mulberry diet can preserve the cardiac function in experimental autoimmune myocarditis by modulating oxidative stress induced MAPK activation and further afford protection against endoplasmic reticulum stress mediated apoptosis.

No MeSH data available.


Related in: MedlinePlus

A–D, Hematoxylin and eosin staining depicting interstitial edema, vacuolization and degeneration of cardiac fibers, TUNEL staining depicting myocardial apoptosis, Azan-Mallory staining for fibrosis (blue area) and cross-sectional cardiac tissue slices with Toluidine blue staining depicting the mast cells respectively (×200). E–G, Bar graph showing the TUNEL positive apoptotic cells (25 fields), % fibrosis and number of mast cells (25 fields). Each bar represents mean ± SEM. Normal, age-matched normal rats; Control, Immunized rats fed with normal diet; ML 5%, Immunized rats administered with normal diet with 5% Mulberry leaf powder. ***p<0.001 vs normal; ###p<0.001 vs control.
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Figure 1: A–D, Hematoxylin and eosin staining depicting interstitial edema, vacuolization and degeneration of cardiac fibers, TUNEL staining depicting myocardial apoptosis, Azan-Mallory staining for fibrosis (blue area) and cross-sectional cardiac tissue slices with Toluidine blue staining depicting the mast cells respectively (×200). E–G, Bar graph showing the TUNEL positive apoptotic cells (25 fields), % fibrosis and number of mast cells (25 fields). Each bar represents mean ± SEM. Normal, age-matched normal rats; Control, Immunized rats fed with normal diet; ML 5%, Immunized rats administered with normal diet with 5% Mulberry leaf powder. ***p<0.001 vs normal; ###p<0.001 vs control.

Mentions: The present study identified a significant suppression of the cardiac function in the EAM rats after three weeks of cardiac myosin injection. There was a significant impairment of the systolic and diastolic components of cardiac contraction as per the hemodynamic and echocardiographic analyses. The control rats demonstrated LV remodeling with increased LV end diastolic pressure (LVEDP), LV dimension in systole (LVDs), LV dimension in diastole (LVDd) and reduced FS in vehicle-treated EAM rats in comparison to control, indicating the impairment of myocardial function. ML treatment has reversed these changes significantly (Table 1). There was a marked inflammatory cellular infiltration and increased myocardial cell size in the control group as identified by histochemical analysis using hematoxylin-eosin staining whereas the ML treated rats showed normal cardiac architecture without much inflammatory cellular infiltration (Fig. 1A).


Modulation of endoplasmic reticulum stress and cardiomyocyte apoptosis by mulberry leaf diet in experimental autoimmune myocarditis rats.

Arumugam S, Thandavarayan RA, Veeraveedu PT, Ma M, Giridharan VV, Arozal W, Sari FR, Sukumaran V, Lakshmanan A, Soetikno V, Suzuki K, Kodama M, Watanabe K - J Clin Biochem Nutr (2011)

A–D, Hematoxylin and eosin staining depicting interstitial edema, vacuolization and degeneration of cardiac fibers, TUNEL staining depicting myocardial apoptosis, Azan-Mallory staining for fibrosis (blue area) and cross-sectional cardiac tissue slices with Toluidine blue staining depicting the mast cells respectively (×200). E–G, Bar graph showing the TUNEL positive apoptotic cells (25 fields), % fibrosis and number of mast cells (25 fields). Each bar represents mean ± SEM. Normal, age-matched normal rats; Control, Immunized rats fed with normal diet; ML 5%, Immunized rats administered with normal diet with 5% Mulberry leaf powder. ***p<0.001 vs normal; ###p<0.001 vs control.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3303476&req=5

Figure 1: A–D, Hematoxylin and eosin staining depicting interstitial edema, vacuolization and degeneration of cardiac fibers, TUNEL staining depicting myocardial apoptosis, Azan-Mallory staining for fibrosis (blue area) and cross-sectional cardiac tissue slices with Toluidine blue staining depicting the mast cells respectively (×200). E–G, Bar graph showing the TUNEL positive apoptotic cells (25 fields), % fibrosis and number of mast cells (25 fields). Each bar represents mean ± SEM. Normal, age-matched normal rats; Control, Immunized rats fed with normal diet; ML 5%, Immunized rats administered with normal diet with 5% Mulberry leaf powder. ***p<0.001 vs normal; ###p<0.001 vs control.
Mentions: The present study identified a significant suppression of the cardiac function in the EAM rats after three weeks of cardiac myosin injection. There was a significant impairment of the systolic and diastolic components of cardiac contraction as per the hemodynamic and echocardiographic analyses. The control rats demonstrated LV remodeling with increased LV end diastolic pressure (LVEDP), LV dimension in systole (LVDs), LV dimension in diastole (LVDd) and reduced FS in vehicle-treated EAM rats in comparison to control, indicating the impairment of myocardial function. ML treatment has reversed these changes significantly (Table 1). There was a marked inflammatory cellular infiltration and increased myocardial cell size in the control group as identified by histochemical analysis using hematoxylin-eosin staining whereas the ML treated rats showed normal cardiac architecture without much inflammatory cellular infiltration (Fig. 1A).

Bottom Line: Mulberry is commonly used as silkworm diet and an alternative medicine in Japan and China, has recently reported to contain many antioxidative flavanoid compounds and having the free radical scavenging effects.Antioxidants reduce cardiac oxidative stress and attenuate cardiac dysfunction in animals with pacing-induced congestive heart failure.ML significantly decreased oxidative stress, myocyte apoptosis, cellular infiltration, cardiac fibrosis, mast cell density, myocardial levels of sarco/endo-plasmic reticulum Ca(2+) ATPase2, p22(phox), receptor for advanced glycation end products, phospho-p38 mitogen activated protein kinase, phospho-c-Jun NH(2)-terminal protein kinase, glucose regulated protein78, caspase12 and osteopontin levels in EAM rats.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, 265-1 Higashizima, Akiha-ku, Niigata 956-8603, Japan.

ABSTRACT
Mulberry is commonly used as silkworm diet and an alternative medicine in Japan and China, has recently reported to contain many antioxidative flavanoid compounds and having the free radical scavenging effects. Antioxidants reduce cardiac oxidative stress and attenuate cardiac dysfunction in animals with pacing-induced congestive heart failure. Hence we investigated the cardioprotective effect of mulberry leaf powder in rats with experimental autoimmune myocarditis. Eight-week-old Lewis rats immunized with cardiac myosin were fed with either normal chow or a diet containing 5% mulberry leaf powder and were examined on day 21. ML significantly decreased oxidative stress, myocyte apoptosis, cellular infiltration, cardiac fibrosis, mast cell density, myocardial levels of sarco/endo-plasmic reticulum Ca(2+) ATPase2, p22(phox), receptor for advanced glycation end products, phospho-p38 mitogen activated protein kinase, phospho-c-Jun NH(2)-terminal protein kinase, glucose regulated protein78, caspase12 and osteopontin levels in EAM rats. These results may suggest that mulberry diet can preserve the cardiac function in experimental autoimmune myocarditis by modulating oxidative stress induced MAPK activation and further afford protection against endoplasmic reticulum stress mediated apoptosis.

No MeSH data available.


Related in: MedlinePlus