Metformin Pretreatment Ameliorates Diabetic Nephropathy Induced by a Combination of High Fat Diet and Streptozotocin in Rats
SUMMARY: Kidney injury secondary to diabetes is the most common cause of kidney failure. We sought to determine whether pretreatment with the insulin-sensitizing drug metformin prior to the induction of diabetes can protect the kidney against the development of diabetic nephropathy (DN) induced by a...
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| Lenguaje: | English |
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Sociedad Chilena de Anatomía
2018
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oai:scielo:S0717-950220180003009692019-09-16Metformin Pretreatment Ameliorates Diabetic Nephropathy Induced by a Combination of High Fat Diet and Streptozotocin in RatsDallak,MohammadBin-Jaliah,IsmaeelAl-Hashem,FahaidKamar,Samaa SKader,Dina H. AbdelAmin,Shaimaa NHaidara,Mohamed AAl-Ani,Bahjat Diabetic nephropathy Metformin Inflammation Rat model SUMMARY: Kidney injury secondary to diabetes is the most common cause of kidney failure. We sought to determine whether pretreatment with the insulin-sensitizing drug metformin prior to the induction of diabetes can protect the kidney against the development of diabetic nephropathy (DN) induced by a combination of a high-fat diet and streptozotocin. Rats were either injected with vehicle (control group) or with a single injection of streptozotocin (STZ) (50 mg/kg) two weeks after being fed on a high-fat diet (HFD) (model group) and continued on HFD until being sacrificed 10 weeks post diabetic induction. The protective group that also fed on a HFD for 12 weeks was put on metformin (200 mg/kg/day) two weeks before STZ injection and continued on metformin until the sacrifice day. Harvested kidney tissues were examined by light microscopy after staining with hematoxylin and eosin (H&E) and periodic acid Schiff (PAS). Blood samples were assayed for sugar, urea, creatinine, and biomarkers of inflammation. Compared to a normal tissue histology in the control group, there was a profound damage to the kidney in the model group as demonstrated by markedly dilated capsular space, increased mesangial matrix expansion, congested blood vessels, and many tubular epithelial cells showing small pyknotic nuclei and vacuolated cytoplasm, which were significantly but not completely protected by metformin. Our findings also show that metformin significantly inhibited the inflammatory biomarkers, tumor necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) induced by diabetes and HFD as well as significantly inhibiting blood sugar, urea, and creatinine. However, the levels of TNF-α, CRP, glucose, and creatinine in the metformin-treated group was still significant to the control group. Thus, we demonstrated an efficient but not complete protection by metformin pretreatment against DN induced by a combination of HFD and streptozotocin in rats.info:eu-repo/semantics/openAccessSociedad Chilena de AnatomíaInternational Journal of Morphology v.36 n.3 20182018-09-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-95022018000300969en10.4067/S0717-95022018000300969 |
| institution |
Scielo Chile |
| collection |
Scielo Chile |
| language |
English |
| topic |
Diabetic nephropathy Metformin Inflammation Rat model |
| spellingShingle |
Diabetic nephropathy Metformin Inflammation Rat model Dallak,Mohammad Bin-Jaliah,Ismaeel Al-Hashem,Fahaid Kamar,Samaa S Kader,Dina H. Abdel Amin,Shaimaa N Haidara,Mohamed A Al-Ani,Bahjat Metformin Pretreatment Ameliorates Diabetic Nephropathy Induced by a Combination of High Fat Diet and Streptozotocin in Rats |
| description |
SUMMARY: Kidney injury secondary to diabetes is the most common cause of kidney failure. We sought to determine whether pretreatment with the insulin-sensitizing drug metformin prior to the induction of diabetes can protect the kidney against the development of diabetic nephropathy (DN) induced by a combination of a high-fat diet and streptozotocin. Rats were either injected with vehicle (control group) or with a single injection of streptozotocin (STZ) (50 mg/kg) two weeks after being fed on a high-fat diet (HFD) (model group) and continued on HFD until being sacrificed 10 weeks post diabetic induction. The protective group that also fed on a HFD for 12 weeks was put on metformin (200 mg/kg/day) two weeks before STZ injection and continued on metformin until the sacrifice day. Harvested kidney tissues were examined by light microscopy after staining with hematoxylin and eosin (H&E) and periodic acid Schiff (PAS). Blood samples were assayed for sugar, urea, creatinine, and biomarkers of inflammation. Compared to a normal tissue histology in the control group, there was a profound damage to the kidney in the model group as demonstrated by markedly dilated capsular space, increased mesangial matrix expansion, congested blood vessels, and many tubular epithelial cells showing small pyknotic nuclei and vacuolated cytoplasm, which were significantly but not completely protected by metformin. Our findings also show that metformin significantly inhibited the inflammatory biomarkers, tumor necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) induced by diabetes and HFD as well as significantly inhibiting blood sugar, urea, and creatinine. However, the levels of TNF-α, CRP, glucose, and creatinine in the metformin-treated group was still significant to the control group. Thus, we demonstrated an efficient but not complete protection by metformin pretreatment against DN induced by a combination of HFD and streptozotocin in rats. |
| author |
Dallak,Mohammad Bin-Jaliah,Ismaeel Al-Hashem,Fahaid Kamar,Samaa S Kader,Dina H. Abdel Amin,Shaimaa N Haidara,Mohamed A Al-Ani,Bahjat |
| author_facet |
Dallak,Mohammad Bin-Jaliah,Ismaeel Al-Hashem,Fahaid Kamar,Samaa S Kader,Dina H. Abdel Amin,Shaimaa N Haidara,Mohamed A Al-Ani,Bahjat |
| author_sort |
Dallak,Mohammad |
| title |
Metformin Pretreatment Ameliorates Diabetic Nephropathy Induced by a Combination of High Fat Diet and Streptozotocin in Rats |
| title_short |
Metformin Pretreatment Ameliorates Diabetic Nephropathy Induced by a Combination of High Fat Diet and Streptozotocin in Rats |
| title_full |
Metformin Pretreatment Ameliorates Diabetic Nephropathy Induced by a Combination of High Fat Diet and Streptozotocin in Rats |
| title_fullStr |
Metformin Pretreatment Ameliorates Diabetic Nephropathy Induced by a Combination of High Fat Diet and Streptozotocin in Rats |
| title_full_unstemmed |
Metformin Pretreatment Ameliorates Diabetic Nephropathy Induced by a Combination of High Fat Diet and Streptozotocin in Rats |
| title_sort |
metformin pretreatment ameliorates diabetic nephropathy induced by a combination of high fat diet and streptozotocin in rats |
| publisher |
Sociedad Chilena de Anatomía |
| publishDate |
2018 |
| url |
http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-95022018000300969 |
| work_keys_str_mv |
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