Amira Awadalla1, Abdelaziz M Hussein2, Yousra M El-Far3, Nashwa Barakat4, Eman T Hamam1, Mohamed El-Sherbiny5, Mohamed El-Shafey6, Ahmed A Shokeir7. 1. Center of Excellence for Genome and Cancer Research, Urology and Nephrology Center, Mansoura University, Mansoura, 35516, Egypt. 2. Medical Physiology Department, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt. Electronic address: zizomenna28@yahoo.com. 3. Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt. 4. Urology and Nephrology Center, Mansoura University, Mansoura, 35516, Egypt. 5. Anatomy department, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt; Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh, Saudi Arabia. 6. Anatomy department, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt; Department of Physiological Sciences, Fakeeh College for Medical Sciences, Jeddah, Saudi Arabia. 7. Center of Excellence for Genome and Cancer Research, Urology and Nephrology Center, Mansoura University, Mansoura, 35516, Egypt; Urology and Nephrology Center, Mansoura University, Mansoura, 35516, Egypt.
Abstract
OBJECTIVES: The present study examined the effects of ferulic acid (FA) and Zinc oxide nanoparticles (ZnO-NPs) and a combination of both on renal ischemia/reperfusion injury (IRI) in rats and their possible underlying mechanisms. METHODS: two-hundreds male Sprague Dawley rats were randomly allocated into the 5 groups; i) sham group, ii) control (IRI) group (occlusion of the left renal pedicle for 45 min), iii) FA group as IRI group with FA (100 mg/Kg oral 24 hrs before ischemia), iv) ZnO-NPs group as IRI group with ZnO-NPs single 5 mg/Kg i.p. 2 hrs before ischemia and v) FA + ZnO-NPs group as IRI group with both FA and ZnO-NPs in the same previous doses. According to the reperfusion times, each group was further subdivided into 4 hr, 24 hr, 48 hr and 7 days reperfusion subgroups. RESULTS: administration of either FA or ZnO-NPs caused significant improvement in the elevated serum creatinine and BUN and malondialdehyde (MDA) concentrations and expression of TNF-α, Bax, caspase-3 in kidney tissues with significant rise in the creatinine clearance, the activities of catalase (CAT) and superoxide dismutase (SOD) and the expression of HO-1, HIF-1α genes and proliferation marker (ki67) in kidney tissues compared to IRI group (p < 0.05). Moreover, a combination of both agents produced more significant improvement in the studied parameters than each agent did alone (p < 0.05). CONCLUSIONS: Both FA and ZnO-NPs exerted cytoprotective effects against ischemic kidney injury and a combination of both exhibited more powerful renoprotective effect. This renoprotective effect might be due to suppression of oxidative stress, enhancement of cell proliferation (ki67), upregulation of antioxidant genes (Nrf2, HO-1 and HIF-1α) and downregulation of inflammatory cytokine (TNF-α) and apoptotic genes (caspase-3 and Bax).
OBJECTIVES: The present study examined the effects of ferulic acid (FA) and Zinc oxide nanoparticles (ZnO-NPs) and a combination of both on renal ischemia/reperfusion injury (IRI) in rats and their possible underlying mechanisms. METHODS: two-hundreds male Sprague Dawley rats were randomly allocated into the 5 groups; i) sham group, ii) control (IRI) group (occlusion of the left renal pedicle for 45 min), iii) FA group as IRI group with FA (100 mg/Kg oral 24 hrs before ischemia), iv) ZnO-NPs group as IRI group with ZnO-NPs single 5 mg/Kg i.p. 2 hrs before ischemia and v) FA + ZnO-NPs group as IRI group with both FA and ZnO-NPs in the same previous doses. According to the reperfusion times, each group was further subdivided into 4 hr, 24 hr, 48 hr and 7 days reperfusion subgroups. RESULTS: administration of either FA or ZnO-NPs caused significant improvement in the elevated serum creatinine and BUN and malondialdehyde (MDA) concentrations and expression of TNF-α, Bax, caspase-3 in kidney tissues with significant rise in the creatinine clearance, the activities of catalase (CAT) and superoxide dismutase (SOD) and the expression of HO-1, HIF-1α genes and proliferation marker (ki67) in kidney tissues compared to IRI group (p < 0.05). Moreover, a combination of both agents produced more significant improvement in the studied parameters than each agent did alone (p < 0.05). CONCLUSIONS: Both FA and ZnO-NPs exerted cytoprotective effects against ischemic kidney injury and a combination of both exhibited more powerful renoprotective effect. This renoprotective effect might be due to suppression of oxidative stress, enhancement of cell proliferation (ki67), upregulation of antioxidant genes (Nrf2, HO-1 and HIF-1α) and downregulation of inflammatory cytokine (TNF-α) and apoptotic genes (caspase-3 and Bax).