Effect of Telmisartan and Quercetin in 5 Fluorouracil-Induced Renal Toxicity in Rats
Harzhin Hiwa Ali,1 Zheen Aorahman Ahmed,2 Tavag Ahmed Aziz2 1Center of Diabetic and Endocrine Diseases, Sulaimani, Iraq; 2Department of Pharmacology and Toxicology, College of Pharmacy, University of Sulaimani, Sulaimani, IraqCorrespondence: Zheen Aorahman Ahmed; Tavag Ahmed Aziz, Tel +9647709724959...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2022-11-01
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| Series: | Journal of Inflammation Research |
| Subjects: | |
| Online Access: | https://www.dovepress.com/effect-of-telmisartan-and-quercetin-in-5-fluorouracil-induced-renal-to-peer-reviewed-fulltext-article-JIR |
| _version_ | 1797985149661478912 |
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| author | Ali HH Ahmed ZA Aziz TA |
| author_facet | Ali HH Ahmed ZA Aziz TA |
| author_sort | Ali HH |
| collection | DOAJ |
| description | Harzhin Hiwa Ali,1 Zheen Aorahman Ahmed,2 Tavag Ahmed Aziz2 1Center of Diabetic and Endocrine Diseases, Sulaimani, Iraq; 2Department of Pharmacology and Toxicology, College of Pharmacy, University of Sulaimani, Sulaimani, IraqCorrespondence: Zheen Aorahman Ahmed; Tavag Ahmed Aziz, Tel +9647709724959 ; +9647701523544, Email zheen.ahmed@univsul.edu.iq; tavga.aziz@univsul.edu.iqPurpose: The present study was designed to evaluate the possible synergistic effects of telmisartan and quercetin in 5 fluorouracil (5-FU) induced nephrotoxicity in rats.Methodology: Forty male rats were randomly divided into five groups: The negative control group, the positive control group that received 5-FU, the telmisartan group, receiving 10 mg/kg, the quercetin group, receiving 80 mg/kg, and the combination of telmisartan and quercetin group. All the treatments were given orally for 14 days. A single intraperitoneal injection of 5-FU (150 mg/kg) on day 13 of the experiment was given except for the negative control group. On the 15th day after scarification, approximately 5 mL of blood was collected and used for measurement of CBC, urea, creatinine, and uric acid. The kidneys were used for histopathological examination and for the measurement of kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), Cystatin C (Cys-C), and total antioxidant capacity (TAOC).Results: The combination therapy significantly attenuated the levels of tissue KIM-1, NGAL, Cys-C, and serum uric acid as well as blood inflammatory markers, Neutrophil/Lymphocyte (NLR), Monocyte/Lymphocyte (MLR), and Platelets/Lymphocyte ratios (PLR), and restored the TAOC. The histopathological findings greatly support the biochemical tests.Conclusion: The results strongly suggest the renoprotective effects of telmisartan and quercetin in combination against the nephrotoxic effect of 5-FU through decreasing the levels of KIM-1, NGAL, and cys-C, and the novel inflammatory markers of kidney injury like NLP, MLR, and PLR, as well as decreasing uric acid and restoring the TAOC. The proposed mechanism could be the additive inhibitory effect on RAS provided by both telmisartan and quercetin.Graphical Abstract: Keywords: nephrotoxicity, telmisartan, quercetin, inflammatory markers, KIM-1, NGAL |
| first_indexed | 2024-04-11T07:14:00Z |
| format | Article |
| id | doaj.art-fc4a546468a34022867c6299ac22d1a5 |
| institution | Directory Open Access Journal |
| issn | 1178-7031 |
| language | English |
| last_indexed | 2024-04-11T07:14:00Z |
| publishDate | 2022-11-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Journal of Inflammation Research |
| spelling | doaj.art-fc4a546468a34022867c6299ac22d1a52022-12-22T04:38:04ZengDove Medical PressJournal of Inflammation Research1178-70312022-11-01Volume 156113612479492Effect of Telmisartan and Quercetin in 5 Fluorouracil-Induced Renal Toxicity in RatsAli HHAhmed ZAAziz TAHarzhin Hiwa Ali,1 Zheen Aorahman Ahmed,2 Tavag Ahmed Aziz2 1Center of Diabetic and Endocrine Diseases, Sulaimani, Iraq; 2Department of Pharmacology and Toxicology, College of Pharmacy, University of Sulaimani, Sulaimani, IraqCorrespondence: Zheen Aorahman Ahmed; Tavag Ahmed Aziz, Tel +9647709724959 ; +9647701523544, Email zheen.ahmed@univsul.edu.iq; tavga.aziz@univsul.edu.iqPurpose: The present study was designed to evaluate the possible synergistic effects of telmisartan and quercetin in 5 fluorouracil (5-FU) induced nephrotoxicity in rats.Methodology: Forty male rats were randomly divided into five groups: The negative control group, the positive control group that received 5-FU, the telmisartan group, receiving 10 mg/kg, the quercetin group, receiving 80 mg/kg, and the combination of telmisartan and quercetin group. All the treatments were given orally for 14 days. A single intraperitoneal injection of 5-FU (150 mg/kg) on day 13 of the experiment was given except for the negative control group. On the 15th day after scarification, approximately 5 mL of blood was collected and used for measurement of CBC, urea, creatinine, and uric acid. The kidneys were used for histopathological examination and for the measurement of kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), Cystatin C (Cys-C), and total antioxidant capacity (TAOC).Results: The combination therapy significantly attenuated the levels of tissue KIM-1, NGAL, Cys-C, and serum uric acid as well as blood inflammatory markers, Neutrophil/Lymphocyte (NLR), Monocyte/Lymphocyte (MLR), and Platelets/Lymphocyte ratios (PLR), and restored the TAOC. The histopathological findings greatly support the biochemical tests.Conclusion: The results strongly suggest the renoprotective effects of telmisartan and quercetin in combination against the nephrotoxic effect of 5-FU through decreasing the levels of KIM-1, NGAL, and cys-C, and the novel inflammatory markers of kidney injury like NLP, MLR, and PLR, as well as decreasing uric acid and restoring the TAOC. The proposed mechanism could be the additive inhibitory effect on RAS provided by both telmisartan and quercetin.Graphical Abstract: Keywords: nephrotoxicity, telmisartan, quercetin, inflammatory markers, KIM-1, NGALhttps://www.dovepress.com/effect-of-telmisartan-and-quercetin-in-5-fluorouracil-induced-renal-to-peer-reviewed-fulltext-article-JIRnephrotoxicitytelmisartanquercetininflammatory markerskim-1ngal |
| spellingShingle | Ali HH Ahmed ZA Aziz TA Effect of Telmisartan and Quercetin in 5 Fluorouracil-Induced Renal Toxicity in Rats Journal of Inflammation Research nephrotoxicity telmisartan quercetin inflammatory markers kim-1 ngal |
| title | Effect of Telmisartan and Quercetin in 5 Fluorouracil-Induced Renal Toxicity in Rats |
| title_full | Effect of Telmisartan and Quercetin in 5 Fluorouracil-Induced Renal Toxicity in Rats |
| title_fullStr | Effect of Telmisartan and Quercetin in 5 Fluorouracil-Induced Renal Toxicity in Rats |
| title_full_unstemmed | Effect of Telmisartan and Quercetin in 5 Fluorouracil-Induced Renal Toxicity in Rats |
| title_short | Effect of Telmisartan and Quercetin in 5 Fluorouracil-Induced Renal Toxicity in Rats |
| title_sort | effect of telmisartan and quercetin in 5 fluorouracil induced renal toxicity in rats |
| topic | nephrotoxicity telmisartan quercetin inflammatory markers kim-1 ngal |
| url | https://www.dovepress.com/effect-of-telmisartan-and-quercetin-in-5-fluorouracil-induced-renal-to-peer-reviewed-fulltext-article-JIR |
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