Wassef, M. A. A., O. M. Tork, L. A. Rashed, W. Ibrahim, H. Morsi, and D. M. M. Rabie, "Mitochondrial Dysfunction in Diabetic Cardiomyopathy: Effect of Mesenchymal Stem Cell with PPAR-γ Agonist or Exendin-4.", Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association, 2017 Apr 27. Abstract

Therapy targeting mitochondria may provide novel ways to treat diabetes and its complications. Bone marrow-derived mesenchymal stem cells (MSCs), the peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists and exendin-4; an analog of glucagon-like peptide-1 have shown cardioprotective properties in many cardiac injury models. So, we evaluated their effects in diabetic cardiomyopathy (DCM) in relation to mitochondrial dysfunction. This work included seven groups of adult male albino rats: the control group, the non-treated diabetic group, and the treated diabetic groups: one group was treated with MSCs only, the second with pioglitazone only, the third with MSCs and pioglitazone, the forth with exendin-4 only and the fifth with MSCs and exendin-4. All treatments were started after 6 weeks from induction of diabetes and continued for the next 4 weeks. Blood samples were collected for assessment of glucose, insulin, and cardiac enzymes. Hearts were removed and used for isolated heart studies, and gene expression of: myocyte enhancer factor-2 (Mef2), peroxisome proliferator-activated receptor gamma coactivator1-alpha (PGC1α), nuclear factor kappa B (NFKB) and autophagic markers: light chain 3 (LC3) and beclin by real-time reverse transcription-polymerase chain reaction. The cardiac mitochondrial protein levels of cardiolipin and uncoupler protein 2 (UCP2) were assessed by ELISA and western blot technique, respectively. Treated groups showed significant improvement in left ventricular function associated with improvement in the cardiac injury and myopathic markers compared to the non treated diabetic group. NFKB was down-regulated while cardiolipin, PGC1α, LC.3 and beclin were up-regulated in all treated groups. These data suggest that the cardioprotective effects of MSCs, exendin-4 or pioglitazone based on their ability to improve mitochondrial functions through targeting inflammatory and autophagy signaling. The co- administration of pioglitazone or exendin-4 with MSCs showed significant superior improvement compared with MSCs alone, indicating the ability to use them in supporting cardioprotective effects of MSCs.

Wassef, M. A. A., O. M. Tork, L. A. Rashed, W. Ibrahim, H. Morsi, and D. M. M. Rabie, "Mitochondrial Dysfunction in Diabetic Cardiomyopathy: Effect of Mesenchymal Stem Cell with PPAR-γ Agonist or Exendin-4.", Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association, 2017 Apr 27. Abstract

Therapy targeting mitochondria may provide novel ways to treat diabetes and its complications. Bone marrow-derived mesenchymal stem cells (MSCs), the peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists and exendin-4; an analog of glucagon-like peptide-1 have shown cardioprotective properties in many cardiac injury models. So, we evaluated their effects in diabetic cardiomyopathy (DCM) in relation to mitochondrial dysfunction. This work included seven groups of adult male albino rats: the control group, the non-treated diabetic group, and the treated diabetic groups: one group was treated with MSCs only, the second with pioglitazone only, the third with MSCs and pioglitazone, the forth with exendin-4 only and the fifth with MSCs and exendin-4. All treatments were started after 6 weeks from induction of diabetes and continued for the next 4 weeks. Blood samples were collected for assessment of glucose, insulin, and cardiac enzymes. Hearts were removed and used for isolated heart studies, and gene expression of: myocyte enhancer factor-2 (Mef2), peroxisome proliferator-activated receptor gamma coactivator1-alpha (PGC1α), nuclear factor kappa B (NFKB) and autophagic markers: light chain 3 (LC3) and beclin by real-time reverse transcription-polymerase chain reaction. The cardiac mitochondrial protein levels of cardiolipin and uncoupler protein 2 (UCP2) were assessed by ELISA and western blot technique, respectively. Treated groups showed significant improvement in left ventricular function associated with improvement in the cardiac injury and myopathic markers compared to the non treated diabetic group. NFKB was down-regulated while cardiolipin, PGC1α, LC.3 and beclin were up-regulated in all treated groups. These data suggest that the cardioprotective effects of MSCs, exendin-4 or pioglitazone based on their ability to improve mitochondrial functions through targeting inflammatory and autophagy signaling. The co- administration of pioglitazone or exendin-4 with MSCs showed significant superior improvement compared with MSCs alone, indicating the ability to use them in supporting cardioprotective effects of MSCs.

M.TORK, O. L. A., and N. Eltablawy, "Effect of melatonin on cisplatin induced – kidney injury in rats: Possible role of Autophagy", The Medical Journal of Cairo University, vol. 81, issue 2, 2013. paper_of_melatonin_and_acute_kidney_injury_final___.pdf
Eltablawy, N., and O. L. A. M.TORK, "Neuroprotection of melatonin against lipopolysaccharide induced Alzheimer's disease in male albino rats.", The Medical Journal of Cairo University, vol. 82 March , issue .2, 2014. the_paper_of_melatonin_inad_pre_final.pdf
Tork, O. M., S. N. Amin., and L. A.Rashed, "Melatonin Reduces Endotoxin-Induced Cardiac Injury in Rats", Medical Science And clinical Research, vol. 2, issue 10, pp. 2765-2777, 2014. 38_jmscr.pdf
M.TORK, O. L. A., L. A.Rashed, and A. F. Abdel-Wahab, "Attenuation of oxidative stress by tamoxifen in the heart of ovarectomized rats with experimentally induced hyperthyroidism.", The Medical Journal of Cairo University, vol. 78, issue 2, pp. 81-92, 2010.
El-Beshbishy, H. A., O. L. A. M.TORK, M. F. EL-Bab, and M. A. Autifi:, "Antioxidant and antiapoptotic effects of green tea polyphenols in azathioprine-induced liver injury in rats", PATHOPHYSIOLOGY journal-JAPAN, vol. Sept., 2010. antiapoptotic_effect_of_green_tea.pdf
MAHMOUD, H. E. S. H. A. M., O. L. A. M.TORK, and A. M. A. N. I. EL-AMIN, "Cardioprotective Effect of vitamin E against Thyroid hormone –Induced Oxidative Stress in Rabbits", The Medical Journal of Cairo University, vol. March, 2009.
Shawky, H. M., Z. A. El-Wahab, and O. Tork, "The effect of peroxisome proliferator – activated gamma agonist on resistin in obese rats with type 2 diabetes", The Medical Journal of Cairo University, vol. 76, issue 2, pp. 337-342, 2008.
Mobarak, H. A., H. M. Shawky, and O. Tork, "Gene expression of Vasopressin receptors type 2 and aquaporin 2 in acute renal failure versus chronic renal failure in rats", The Medical Journal of Cairo University, vol. 76, issue 2, pp. 373-380, 2008.
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