The current study investigated the effect of upregulation of heme oxygenase 1 (HO-1) by cobalt protoporphyrin (CoPP) on renal dysfunctions in renal ischemia/reperfusion (I/R) injury and its underlying mechanisms. 72 male Sprague Dawley rats were divided into 4 groups: sham group, ischemic group (left 45-min renal ischemia), CoPP-before group (as ischemic group with CoPP 20 mg/ kg 30 min before ischemia) and CoPP-after group (as ischemic group with CoPP 20 mg/kg 20 min after ischemia). Serum creatinine, urea and TGF-β1 and markers of redox state (MDA, SOD, GSH and CAT), nitric oxide (NO), TGF-β1 and HO-1 in kidney tissues were measured. Serum creatinine and urea levels were significantly increased in ischemic group and attenuated in CoPP-treated groups (p < 0.05). Also, markers of redox state showed significant deteriorations in ischemic group which were improved significantly in CoPP-treated groups (p < 0.05). HO-1 expression in kidney tissues showed significant increase in ischemic group and showed more significant increase in CoPP-treated groups (p < 0.05). Moreover, serum and renal TGF-β1 levels were significantly increased in ischemic group and attenuated in CoPP-treated groups (p < 0.05). We concluded that up-regulation of HO-1 by CoPP treatment before and after renal I/R injury improved the kidney function and morphology and this might be due to impairment of oxidative stress and inflammatory cytokines in kidney tissues.
Background
Liver fibrosis is a major medical problem with high mortality and morbidity rates where the formation of regenerative nodules and cirrhosis leads to loss of liver function and may result in the development of hepatocellular carcinoma. bone marrow mesenchymal stem cells (BM-MSCs) have drawn attention as a novel approach for treatment of liver fibrosis. This study aimed to evaluate the therapeutic effect of BM-MSCs on the liver structure in carbon tetrachloride (CCl
4
) induced liver fibrosis in male rats relative to resveratrol and
Silybum marianum
as standard drugs derived from herbal plants.
Methods
Fifty adult male albino rats (Sprague Dawley strain; 180–220 g mean body weight) were purchased from the Laboratory Animal Unit in the Nile Center of Experimental Research, Mansoura, Egypt. Liver function were determined, isolation and preparation of BM- MSCs and detection of cell-surface markers by flow cytometry.
Results
Animals exposed to CCl
4
developed liver injury characterized by significant increase of liver enzymes, malondialdehyde (MDA), tumor necrosis factor alpha (TNFα), and CYP450, inhibition of antioxidant enzymes, and decreased albumin. Treatment with stem cells enhanced liver state more effectively than resveratrol and
S. marianum
. It significantly decreased AST, ALT, ALP, MDA, TNF-α, and CYP450 and increased albumin, SOD, GSH, GST, and CAT. Histopathological study and atomic force microscope results confirmed the therapeutic effects of MSCs.
Conclusions
BM-MSCs could restore liver structure and function in CCL
4
induced liver fibrosis rat model, ameliorating the toxicity of CCl
4
and improving liver function tests.
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