Protective effect of rutin supplementation against cisplatin-induced Nephrotoxicity in rats
Abstract Background Cisplatin (CP) is commonly used in the treatment of different types of cancer but nephrotoxicity has been a major limiting factor. Therefore, the present study aimed to study the possible protective effect of rutin against nephrotoxicity induced by cisplatin in rats. Methods Fort...
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| Format: | Article |
| Language: | English |
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BMC
2017-06-01
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| Series: | BMC Nephrology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12882-017-0601-y |
| _version_ | 1818178597624479744 |
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| author | Ali R. Alhoshani Mohamed M. Hafez Sufia Husain Abdel Malek Al-sheikh Moureq R. Alotaibi Salim S. Al Rejaie Musaad A. Alshammari Mashal M. Almutairi Othman A. Al-Shabanah |
| author_facet | Ali R. Alhoshani Mohamed M. Hafez Sufia Husain Abdel Malek Al-sheikh Moureq R. Alotaibi Salim S. Al Rejaie Musaad A. Alshammari Mashal M. Almutairi Othman A. Al-Shabanah |
| author_sort | Ali R. Alhoshani |
| collection | DOAJ |
| description | Abstract Background Cisplatin (CP) is commonly used in the treatment of different types of cancer but nephrotoxicity has been a major limiting factor. Therefore, the present study aimed to study the possible protective effect of rutin against nephrotoxicity induced by cisplatin in rats. Methods Forty male Wistar albino rats were randomly divided into 4 groups. Rats of group 1 control group intraperitoneal (i.p.) received 2.5 ml/kg, group 2 CP group received single dose 5 mg/kg cisplatin i.p. group 3 rutin group orally received 30 mg/kg rutin group 4 (CP plus rutin) received CP and rutin as in group 2 and 3. Kidneys were harvested for histopathology and for the study the gene expression of c-Jun N-terminal kinases (JNK), Mitogen-activated protein kinase 4 (MKK4), MKK7, P38 mitogen-activated protein kinases (P38), tumor necrosis factors alpha (TNF-α), TNF Receptor-Associated Factor 2 (TRAF2), and interleukin-1 alpha (IL-1-α). Results The cisplatin single dose administration to rats induced nephrotoxicity associated with a significant increase in blood urea nitrogen (BUN) and serum creatinine and significantly increase Malondialdehyde (MDA) in kidney tissues by 230 ± 5.5 nmol/g compared to control group. The animal treated with cisplatin showed a significant increase in the expression levels of the IL-1α (260%), TRFA2 (491%), P38 (410%), MKK4 (263%), MKK7 (412%), JNK (680%) and TNF-α (300%) genes compared to control group. Additionally, histopathological examination showed that cisplatin-induced interstitial congestion, focal mononuclear cell inflammatory, cell infiltrate, acute tubular injury with reactive atypia and apoptotic cells. Rutin administration attenuated cisplatin-induced alteration in gene expression and structural and functional changes in the kidney. Additionally, histopathological examination of kidney tissues confirmed gene expression data. Conclusion The present study suggested that the anti-oxidant and anti-inflammatory effect of rutin may prevent CP-induced nephrotoxicity via decreasing the oxidative stress, inhibiting the interconnected ROS/JNK/TNF/P38 MAPK signaling pathways, and repairing the histopathological changes against cisplatin administration. |
| first_indexed | 2024-12-11T20:50:31Z |
| format | Article |
| id | doaj.art-c92d3a4cb2634616989936dda6a15256 |
| institution | Directory Open Access Journal |
| issn | 1471-2369 |
| language | English |
| last_indexed | 2024-12-11T20:50:31Z |
| publishDate | 2017-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Nephrology |
| spelling | doaj.art-c92d3a4cb2634616989936dda6a152562022-12-22T00:51:15ZengBMCBMC Nephrology1471-23692017-06-0118111010.1186/s12882-017-0601-yProtective effect of rutin supplementation against cisplatin-induced Nephrotoxicity in ratsAli R. Alhoshani0Mohamed M. Hafez1Sufia Husain2Abdel Malek Al-sheikh3Moureq R. Alotaibi4Salim S. Al Rejaie5Musaad A. Alshammari6Mashal M. Almutairi7Othman A. Al-Shabanah8Department of Pharmacology and Toxicology, College of Pharmacy, King Saud UniversityDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud UniversityDepartment of Pathology, College of Medicine, King Saud UniversityDepartment of Pathology, College of Medicine, King Saud UniversityDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud UniversityDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud UniversityDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud UniversityDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud UniversityDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud UniversityAbstract Background Cisplatin (CP) is commonly used in the treatment of different types of cancer but nephrotoxicity has been a major limiting factor. Therefore, the present study aimed to study the possible protective effect of rutin against nephrotoxicity induced by cisplatin in rats. Methods Forty male Wistar albino rats were randomly divided into 4 groups. Rats of group 1 control group intraperitoneal (i.p.) received 2.5 ml/kg, group 2 CP group received single dose 5 mg/kg cisplatin i.p. group 3 rutin group orally received 30 mg/kg rutin group 4 (CP plus rutin) received CP and rutin as in group 2 and 3. Kidneys were harvested for histopathology and for the study the gene expression of c-Jun N-terminal kinases (JNK), Mitogen-activated protein kinase 4 (MKK4), MKK7, P38 mitogen-activated protein kinases (P38), tumor necrosis factors alpha (TNF-α), TNF Receptor-Associated Factor 2 (TRAF2), and interleukin-1 alpha (IL-1-α). Results The cisplatin single dose administration to rats induced nephrotoxicity associated with a significant increase in blood urea nitrogen (BUN) and serum creatinine and significantly increase Malondialdehyde (MDA) in kidney tissues by 230 ± 5.5 nmol/g compared to control group. The animal treated with cisplatin showed a significant increase in the expression levels of the IL-1α (260%), TRFA2 (491%), P38 (410%), MKK4 (263%), MKK7 (412%), JNK (680%) and TNF-α (300%) genes compared to control group. Additionally, histopathological examination showed that cisplatin-induced interstitial congestion, focal mononuclear cell inflammatory, cell infiltrate, acute tubular injury with reactive atypia and apoptotic cells. Rutin administration attenuated cisplatin-induced alteration in gene expression and structural and functional changes in the kidney. Additionally, histopathological examination of kidney tissues confirmed gene expression data. Conclusion The present study suggested that the anti-oxidant and anti-inflammatory effect of rutin may prevent CP-induced nephrotoxicity via decreasing the oxidative stress, inhibiting the interconnected ROS/JNK/TNF/P38 MAPK signaling pathways, and repairing the histopathological changes against cisplatin administration.http://link.springer.com/article/10.1186/s12882-017-0601-yCisplatinNephrotoxicityP38 MAPKGene expression |
| spellingShingle | Ali R. Alhoshani Mohamed M. Hafez Sufia Husain Abdel Malek Al-sheikh Moureq R. Alotaibi Salim S. Al Rejaie Musaad A. Alshammari Mashal M. Almutairi Othman A. Al-Shabanah Protective effect of rutin supplementation against cisplatin-induced Nephrotoxicity in rats BMC Nephrology Cisplatin Nephrotoxicity P38 MAPK Gene expression |
| title | Protective effect of rutin supplementation against cisplatin-induced Nephrotoxicity in rats |
| title_full | Protective effect of rutin supplementation against cisplatin-induced Nephrotoxicity in rats |
| title_fullStr | Protective effect of rutin supplementation against cisplatin-induced Nephrotoxicity in rats |
| title_full_unstemmed | Protective effect of rutin supplementation against cisplatin-induced Nephrotoxicity in rats |
| title_short | Protective effect of rutin supplementation against cisplatin-induced Nephrotoxicity in rats |
| title_sort | protective effect of rutin supplementation against cisplatin induced nephrotoxicity in rats |
| topic | Cisplatin Nephrotoxicity P38 MAPK Gene expression |
| url | http://link.springer.com/article/10.1186/s12882-017-0601-y |
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